Ceramics International xxx (xxxx) xxx

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Ceramics International
journal homepage: www.elsevier.com/locate/ceramint

Ceramic biomaterials: Properties, state of the art and future prospectives

Shivani Punj a, Jashandeep Singh b, K. Singh a, *
a
School of Physics and Materials Science, Thapar Institute of Engineering and Technology, Patiala, 147004, India
b
Department of Physics, Gulzar Group of Institutes, Ludhiana, 141001, India

A R T I C L E I N F O A B S T R A C T

Keywords: This article gives an overview of ceramics-based biomaterials with particular emphasis on their various prop­
Bioceramics erties and health care applications. Furthermore, bio ceramics are grouped as oxide and nitride-based bioinert
Toxicity ceramics, bioresorbable calcium phosphate-based materials and bioactive glasses/glass ceramics. Ceramics and
Bioactivity
bioglasses are good biomaterials, here mainly focused on bone replacement applications. Mesoporous glasses,
Antibacterial
Agro-food wastes based
nanocrystalline ceramics and composites, having a high surface area, corrosion resistive and better mechanical
Bioglasses/glass ceramics properties, could be future biomaterials. Controlled porosity with uniform pores distributed biomaterials could
be achieved using fine synthesis routes like sol-gel and additive manufacturing. Bioceramics and bioglasses could
also be synthesized by agro-food wastes and optimize their properties according to need and applications easily.
Moreover, these sustainable resources exhibit inherent porosity due to presence of organic substance attached
with inorganic materials. As crystallinity increased, the bioactivity decreases of ceramics. Both properties can be
optimised using nano-crystalline and composite biomaterials.

1. Introduction
Bioceramics can be synthetic or natural in origin that are designed to
make bonds with bone and have appeared as an alternative to metallic
implants [1]. Ceramics are defined as oxides, nitrides, sulphides and
carbides of metals and metalloids [2]. These are important in the
biomedical field due to their good and matchable physio-chemical
properties with some of the human body parts. Initially, bioceramics
porcelain was used in crown treatment during the 18th century. Then, in
the 19th century, plaster of Paris was used in the dentistry application [3,
4] The applications of ceramics increased many fold in the medical field
in the 20th century due to processing technology advancements [5].
Bioceramic materials having excellent biocompatibility, poor degrad­
ability, high melting temperature, non-corrosive, better mechanical
properties with poor plasticity than metal-based biomaterials. Bio­
ceramics are hard and fragile and low fracture toughness along with
elastic modulus in comparison with bone [6–9]. Concerning synthetic
bioceramics such as alumina, zirconia, titania, Ca–P based porous ma­
terials, bioactive glasses/glass-ceramics are used in dentistry, orthopae­
dics, calcified tissues, implants, coatings, medical sensors, and many
other applications [10–13]. The use of bioceramics also provides a new
horizon in the context of soft tissue repair and regeneration [14].
Bioglasses/glass-ceramics have emerged as a versatile material that
can be moulded according to the requirement of the users. The value of
bioglasses/glass-ceramics is becoming a huge market demand, approxi­
mately 1.5 million per annum at a cost of $ 10 billion [15]. Silica based
bioglasses have been extensively studied over the last decades. Borate,
borosilicate, borophosphate and other combinations with different ther­
apeutic elements-based compositions provide novel approaches for
different applications. This will also result in the increasing penetration of
bioglasses/glass-ceramics in the orthopaedic and dental sector. Advanced
approaches also involve the use of bioglasses/glass-ceramics as 3D scaf­
folds, as coating of implants, and composites that show comparable me­
chanical properties to natural bones [15]. Any biomaterial must be
biocompatible and exhibit antibacterial properties. It is very herculean
task to develop proper biomaterials according to needs and application.
For instance, adding some dopants in major composition of glass and glass
ceramics influence various properties but at the same time, they retard
other properties. Therefore, a balance between various properties is
required for proper selection of materials, their constitutes, concentration,

* Corresponding author.
E-mail address: kusingh@thapar.edu (K. Singh).

https://doi.org/10.1016/j.ceramint.2021.06.238
Received 7 May 2021; Received in revised form 17 June 2021; Accepted 27 June 2021
Available online 30 June 2021
0272-8842/© 2021 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

Please cite this article as: Shivani Punj, Ceramics International, https://doi.org/10.1016/j.ceramint.2021.06.238
S. Punj et al.
process parameters and design. For example, in case of bioglass,
biocompatibility and antibacterial activity could be increased by dopants
in the matrix. However, as high dose of doped ions can cause toxicity in
the body. Ceramic based biomaterials exhibit some advantages over
metals and alloys like density, porosity, high elastic modulus, hardness
and low cost. But they also have some demerits like poor sinterability,
ductility and machinability. These properties restrict their use as bio­
materials. Mostly, these synthetically derived bioglasses/glass-ceramics
are fabricated using costly minerals. Recently, sustainable natural bio­
ceramics such as agro wastes/ashes (rice husk ash (RHA), sugarcane leave
ash (SCLA), corn cob (CC)) are also used as an attractive source of silica
that can be transformed into cost effective value added biogenic silica
nanoparticles and bioglasses/glass-ceramics [16,17]. Similarly, food
wastes such as egg shell powder (ESP), egg shell membrane (ESM) contain
calcium (Ca) and banana peel (BP) contain potassium (K), polyphenolic
compounds, and essential amino acids which can be used for the pro­
duction of β-tricalcium phosphate (β-TCP), biphasic calcium phosphate
(BCP), hydroxyapatite (HAp), mesoporous bioglasses, alternative to syn­
thetic bioglasses used for prosthesis and medical therapies [17–19].
Synthetic minerals also combined with agro-food waste/ashes proven to
serve as biomaterial substitutes for different biomedical applications.
Agro-food wastes derived bioglasses/glass-ceramics have provided more
advantages as compared to synthetic bioglasses. The selection of initial
constituents and their amount play vital role to qualify as a biomaterial.
By changing in process parameters and advent in various synthetic tech­
niques, further, enhanced and overcome the disadvantages of ceramic
materials. The present review article is related to synthetic bio ceramics,
their fabrication and bioactivity testing techniques. The various additives,
dopants and changes in process parameters and their effect on various
bioactive and other associate properties are also overviewed in this
article. In second last section, the detail study on agro-food waste/ashes
Fig. 1. Classification of bio-ceramic materials, mechanical and physical properties correspond to their interaction occur in physiological environment during body
implants and tissues.
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derived bio glasses/glass-ceramics is given followed by important findings
and future prospective of the bio ceramics.
2. Synthetic bioceramics
Synthetic ceramic materials are classified into sub parts as bioinert,
bioactive, and bioresorbable corresponds to the type of interaction occur
in physiological environment during body implants and tissues, as
shown in Fig. 1. Synthetic bioceramics are being used for making im­
plants, drug delivery carrier, teeth fillers, stents, heart valve, etc. The
advancement in process technology means the physical, structural and
mechanical properties can be tailored according to the needs of the body
parts and applications. The following sections explained the synthetic
ceramic biomaterials according to their health care applications.
2.1. Bioinert ceramics
Bioinert ceramics do not show a biological response with surround­
ing tissues. It has the ability to resist corrosion in a physiological envi­
ronment. The examples of oxide bioinert ceramics are alumina, and
partially stabilized zirconia and non-oxide bioinert ceramics are carbon
and nitride-based ceramics.
2.1.1. Alumina
Alumina is generally used for orthopaedic and dental implants. It has
good mechanical strength, a low friction coefficient and biocompati­
bility in the human body. According to the American Society for Testing
and Materials, which is an international standards organization (ASTM/
ISO) F603-12, some standard specifications of bioinert materials to be
used in clinical applications are given in Fig. 1 [20]. Some of the me­
chanical properties of materials depend upon grain size and porosity,
S. Punj et al.
small the grain size and low porosity of materials showed good me­
chanical strength [11]. Zhao et al. synthesized an alumina < 1 μm grain
size and <0.7% porosity led to its translucent nature. Porosity promotes
osteointegration and bone growth for the special implants [21–23].The
incorporation of magnesia (MgO) or calcia (CaO) enabled the alumina to
be sintered at a temperature lower than 1600 ◦ C by enhancing the solid
state diffusion method [23]. Alumina is also used to fabricate nano­
composites by using different materials such as alumina/Ti, hydroxy­
apatite (HAp)/alumina, graphene platelets/alumina-based materials to
study their biomechanical, cytocompatibile and m-RNA gene expression
behaviour using a digital histology index [24–26]. Alumina, when used
as implants, is unable to bond with soft and hard tissues. In order to
overcome this issue, SiAlON–Al2O3 ceramics fabricated via direct nitri­
dation method provide suitable porosity, compressive strength and
biocompatibility [27].
2.1.2. Zirconia
Zirconia is an allotropic oxide, occurred in three crystal structures
monoclinic (1170 ◦ C), tetragonal (2370 ◦ C), and cubic (2680 ◦ C)
depending on the temperature. It has been noted that various oxides
used as a zirconia stabilizer, such as CaO, MgO, CeO2 and yttria (Y2O3).
Some studies reported the combinations of Y2O3 stabilized zirconia and
titania nanotubes exhibited a novel approach to studying tribological
characterizations, wear and friction rate for orthopaedic applications
[28–31]. It has been often preferred in dentistry (pins, crowns, bridges,
veneers and orthodontic brackets) due to its mechanical properties as
well as colour, which match the shade of natural teeth [32]. However,
zirconia has some shortcomings, degradation occur with increase of time
in a human body due to its crystalline phase transformation [33]. In
addition of this, the combination of alumina-zirconia composites is also
used to lower the zirconia transformation kinetics [27]. Titania (TiO2) is
used to enhance the sintering and ceramic performance of these com­
posites. It showed excellent bioactivity due to its non-corrosive nature. It
also helps to promote the attachment of implants to bone tissues in a
short time. A recent study also demonstrated the effect of TiO2 addition
on the microstructure of alumina, zirconia, and cerium based ceramic
composites. These are prepared by a pressure less, low temperature
sintering (1400 ◦ C for 2 h) method. The results showed that increasing
the TiO2 content (5 wt%) increased the relative density. TiO2 has a
strong influence on phase evolution and grain growth during sintering
and can be used in dental applications [34].
2.1.3. Non-oxide bioinert ceramics
Non-oxide bioinert ceramics such as carbon and nitrides are also
used as a biomaterial. But the use of carbon was not much successful for
orthopaedic devices. However, carbon and carbon nano tubes (CNT)
have excellent strength, fracture toughness and good durability. Carbon
has the ability to inhibit the blood clotting at the interface between
material interface and the tissues. These are also used in heart valve
prothesis as well as a coating on the substrates [35]. Carbon nano­
structures also showed great interest in soft tissue engineering and im­
plants, for instance, CNT and graphene are used to repair large gaps in
served nerves [36]. Nitrides such as titania nitride (TiN), titania niobium
nitride (TiNbN), chromium nitride (CrN), zirconia nitride (ZrN) are used
as coatings on metallic components in order to enhance the hardness of
the surface, increase the wettability of metallic components. Inspite of
coating, silicon nitride (Si3N4) ceramics are in progress that used for
spinal surrey and joint replacements [37].
2.2. Bioactive ceramics
Bioactive ceramics exhibit the properties of bioinert and bio­
resorbable ceramic materials. The bone-bonding ability of these mate­
rials is referred to as ‘osteoconductivity’ or ‘bioactivity’. These bioactive
ceramics are also being used as coating materials to enhance the me­
chanical and corrosion resistive properties of bone graft implants, due to
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their osteoconductive properties. They can also act as scaffold to enhance
bone formation on their surfaces. The most common bioactive ceramics
are bioglasses and bioactive glass-ceramics, CaP, HAp. These bioactive
materials are discussed and summarised in the following section.
2.2.1. Bioglasses/glass-ceramics
Bioglass (45S5) (BG) was discovered by Hench et al. [38] in the early
1970s for bone replacement applications. After discovery, a lot of bio
glasses have been reported for various applications such as drug delivery,
hyperthermia, implants, fillers etc. [13]. The original BG composition
(45SiO2-24.5CaO-24.5Na2O–6P2O5 in wt%) is based on silica (Si) as a
glass former that has bonding ability to bone after post implantations
in-vivo. A sequence of 11 reactions steps is included in the bonding pro­
cesses of BG to living tissue [39]. Hench described the 1–5 steps for the
formation of the (hydroxycarbonate apatite) HCA layer on the surface of
glasses. BGs are found to be “bioactive” on the basis of these mechanisms:
(i) the formation of an apatite layer on the surface of BG when it is dis­
solved in a physiological environment, (ii) the release of biologically
active ions in simulated body fluids (SBF)/plasma during in-vitro and
in-vivo testing, respectively. The first “bioactivity” mechanism for the
composition of BG is well defined [39,40]. The interaction of BG surfaces
with body fluids begins with an exchange of ions that leads to an increase
in the testing medium’s pH, resulting in the development of a silica-rich
layer and then the growth of a Ca–P rich layer on the BG surface. This
layer is further combined with carbonates and then crystalizes to form
HCA, which ultimately helps to bond with the bone [39]. The HCA layer
also provides an optimal environment for next 6–11 biological reaction
stages, which include cell colonization, proliferation and differentiation to
form new bone with good mechanical bond to implant surface. The HCA
layer thickness has a major impact on bone bonding ability of the BG as
well as on the interface shear strength. Generally, an interface thickness of
20 μm offers strong shear strength and interfacial bonding [20]. The ac­
tion of BG in the creation of new soft (peripheral nerves, heart, lungs, and
ophthalmology) or hard tissues (bones) greatly depends on the pore size,
surface area, morphology and composition of the glass. The pore size < 1
μm is responsible for better bioactivity, and attachment of cells [41–49]. It
could be achieved by change in process parameters, constituents, and
chemical route like sol-gel method rather than melt-quench method.
Another class of bio ceramics is bioactive glass-ceramics that are formed
through the controlled crystallization of glass at an appropriate temper­
ature. Most of the bioactive glass-ceramics are based on similar compo­
sitions to BG, but bioglass-ceramics exhibit better mechanical and poor
bioactive properties than BG [50]. For instance, commercial cerabone
(A-W) is produced by controlled heat treatment having 38 wt% apatite,
34 wt% of wollastonite and 28 wt% of residual glass phase that is used as
coating for Ti alloys, artificial vertebrae and bone fillers [10,12]. The
action of A-W glass ceramic depends upon different parameters such as
porosity (5.0 ± 0.3), fraction of vitreous phase (28%), hardness (6.9 ±
0.3) and bending strength (215 MPa; 3 points). Particularly, bending
strength of A-W glass ceramic is higher than that of typical human cortical
bone (160 MPa). However, the fracture toughness of this glass ceramic is
three times lower than human cortical bone i.e. 6 MPam1/2 [10]. Other
common examples of bioactive glass-ceramic are ceravital, wollastonite
diopside (WD), diopside and combeite. Wollastonite and diopside phases
are formed when parent glass heat treatment is above 900 ◦ C. Wollas­
tonite also has high thermal, mechanical and biological properties. But it
has a high dissolution rate in in-vitro conditions. On the other hand,
diopside has a slower dissolution rate and high mechanical properties.
Therefore, composites of wollastonite and diopside have been used in
tissue engineering applications. These bioactive glass-ceramics has been
used in bulk, granular and porous form, and are used for bone graft ap­
plications [51]. Therefore, it concluded that properly selected glass ce­
ramics could meet most of the required properties for bone graft and tissue
engineering applications.
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2.3. Bioresorbable ceramics 2.3.2. Calcium phosphate (CaP)

Bioresorbable ceramics are also used in different medical fields
considered as an alternative to metallic and polymeric biomaterials.
Because biodegradable metallic and polymeric materials show local
inflammation by releasing acidic by-products to the human body [52].
Bioresorbable refers to a material that dissolves after being implanted in
the human body and is gradually replaced by advancing tissues (bones).
Calcium sulphate, calcium phosphates (CaP) and their salts, porous HAp,
are the common examples of bioresorbable ceramics. These ceramics are
commonly used to treat the fractured bones without causing in­
flammations [53]. Because of the close relationship between bioactive
and biodegradable materials are often studied together such as CaP and
HAp. Many authors consider both to be second generation bioceramics,
distinguished from first generation, i.e., bioinert, and the third genera­
tion, which corresponds to scaffolds used in bone tissue engineering [51].
2.3.1. Calcium sulphate
It is an inorganic, naturally occurring osteoconductive crystalline
substance. It exists in various hydrate forms such as anhydrite (CaSO4),
hermihydrate state (CaSO4 .0.5H2O) and dihydrate state or gypsum
(CaSO4 .2H2O). Calcium sulphate is used in the form of pellets alone, or
as an injectable suspension, or in combination with other substances. It’s
compressive strength (99.15 MPa) is equivalent to cancellous bone. It is
fragile and rapidly loses its strength when it is hydrolysed. Due to their
injectability and rapid degradability, it has been used as bone grafts as
well as carriers for antibiotics to prevent infection [54].
Different CaP, such as dicalcium phosphate, tricalcium phosphate
(TCP), amorphous hydroxyapatite (ACp), hydroxyapatite (HAp), fluo­
rapatite (FAp), etc. are also used for longer time periods to develop
artificial bone. The CaP based bone grafts degrade slowly as compared to
the calcium sulphate bone graft [54]. These different class of CaP ma­
terials having different solubilities and bioactivity according to their
Ca/P ratio, as shown in Table 1. The biodegradation depends upon
various factors such as chemical composition, physical properties (sur­
face area, porosity, density, volume) and crystal structure, pH stability of
the material. For instance, body centre structured (BCC) materials
dissolve more than face canter structured (FCC) materials. Since BCC less
stable and open crystal structure than FCC. Ceramics grain boundaries
when reabsorbed the material allow to release of micro or nanoparticles
that helps to perform biological reactions, which can be useful in gene
therapy and bone tissue engineering applications [11]. CaP ceramics that
are commonly used for bone tissue engineering are TCP, HAp and
biphasic calcium phosphate (BCP). TCP has two different phases, such as
α -TCP and β-TCP. Numerous studies show that α-TCP dissolves at a faster
rate than β-TCP, but β-TCP mostly used clinically due to its osteo­
conductive and osteoinductive nature [10,53]. In-vivo studies also
demonstrate that resorbability of α-TCP is higher than β TCP during bone
growth for tissue engineering [55,56]. Both phases of TCP are more
bioresorbable than HAp. Sintered HAp is more stable which remains in
the body for a long time after implantation. HAp is extensively used due
to its chemical similarities to inorganic components of bone tissues

Table 1
Different class of CaP materials according to their different Ca/P ratio, cell parameters, pH stability, and density.
Compound Formula Unit cell parameter Ca/P pH Density Remarks Ref
stability g/cc

Monocalcium phosphate Ca(H2PO4)H2O) a = 5.6261(5), 0.5 2 2.33 Not compatible with bones due to higher [52]
monohydrate b = 11.889(2), acidity and solubility.
c = 6.4731 (8) Å,
α = 98.633(6)o,
β = 118.262(6)o,
γ = 83.344(6)o
Dicalcium phosphate CaHPO4.2H2O a = 5.812(2), 1.0 2–6.5 2.32 Non-toxic and anticorrosive, used in [52]
dihydrate b = 15.180(3), pathological calcification, urinary stones
c = 6.239 (2)Å,
β = 116.42(3)o
Octa calcium phosphate Ca8(HPO4)2(PO4).5H2O a = 19.692(4), 1.33 5.5–7 2.61 Stable component, used for enamel mineral
b = 9.523(2), formation, heart valve surgery and urinary
c = 6.835 (2) Å, calculi
α = 90.15(2)o,
β = 92.54(2)o,
γ = 108.65(1)o
TCP (α and β Tricalcium α-Ca3(PO4)2 a = 12.887(2), 1.5 2.86 [54,
phosphate) β-Ca3(PO4)2 b = 27.280(4), 3.08 55]
c = 15.219 (2) Å, β =
126.20(1)o
a = b = 10.4183(5), c =
37.3464(23) Å, γ = 120◦
Amorphous calcium Cax Hy (PO4)z. Temperature dependent, pH solution [54]
phosphate (ACP) nH2O dependent, suitable for soft tissue patho-
logical calcifications
Calcium deficient Ca10-x (HPO4) x(PO4)6-x. 1.5–1.67 6.5–9.5 Used to form artificial bone substitutes, [54]
hydroxyapatite (OH)2-x drug delivery applications
(CDHA)
Hydroxyapatite (HAp) Ca10(PO4)6(OH)2 a = 9.84214(8), 1.67 9.5–12 3.16 Chemical similarity to bone and teeth [54]
b = 2a, c = 6.8814 (7) mineral. Used for hip joint prothesis,
Å,γ = 120◦ (monoclinic) dental implants
a = b = 9.4302 (5),
c = 6.8911(2) Å,
γ = 120◦ (hexagonal)
Fluorapatite (FA) Ca10(PO4)6(F)2 a = b = 9.367, 1.67 7–12 3.20 Hardest, most stable, least soluble. [54]
c = 6.884 Å,
γ = 120◦
Tetra calcium phosphate Ca4(PO4)2O a = 7.023(1), 2.0 3.05 Cannot be precipitated in aqueous sol. [52]
(TTCP) b = 11.986(4), Prepared only in anhydrous conditions.
c = 9.473 (2) Å,
β = 90.90(1)o

4
S. Punj et al.
instead of different crystalline forms of CaP. The major composition of
bone is the mineral phase (69 wt%), organic matrix (22 wt%) and water
(9%). However, it has low bioresorbability, but it helps to form nucle­
ating sites for the precipitations of apatite crystals in the culture medium
[56]. HAp may be natural or synthetic depends on the fabrication
method. HAp powders can also be manufactured using different methods
that gives different particle sizes and shapes such as hydrothermal (HAp
whiskers of 10 μm width and 150 μm length), precipitation (nano rods of
50 nm and nano spheres of 200 nm in size), solid state reaction >1200 ◦ C
(nanoparticles of 50–100 nm), sol-gel method (sintered HAp nano crys­
tals of 50–70 nm in size), emulsion method (spherical nanoparticles of 18
nm in size) [20,57]. HAp ceramics also has lower mechanical strength
than inert ceramics, so, it cannot be used for load bearing applications in
the human body. The mechanical properties of HAp also depend upon
density, porosity, sinterability, phase composition, and crystal size. The
Vickers’s hardness of dense HAp lies in the range 3–7 GPa, and the
Weibull’s modulus lie in the range 5–18, which are characteristic of
fragile materials [58]. Various elements (Si, Mg, Sr, Zn) subsituted in
HAp to enhance its mechanical properties [56,57,59]. Similarly, different
studies showed that CNTs were also substituted in HAp composites, that
provide an opportunity to enhance the fracture toughness, replace
collagen fibres as structural stiffeners for bone scaffolds, and enhanced
apatite mineralization [60–63]. Despite the fact that HAp’s biocompati­
bility is well known, but the use of HAp for a prolonged time as a coated
metallic implant is still a challenge. This is due to during coating prep­
arations, thermal stresses (due to difference of coefficient of thermal
expansion) produced at ceramic-metallic interface [20]. HAp has good
biological activity, but it has slow degradation rate in-vivo. On the other
hand.
β-TCP has fast degradation rate with poor mechanical properties.
Therefore, the combination of HAp and β-TCP phase called BCP ceramic
is used as a regenerative material, drug delivery system and repair of
complex bone defects due to its gradual dissolution in the medium [64].
High reactivity of BCP showed dynamic evolution from a rhombohedral
to a hexagonal structure [64]. Similarly, BCP synthesized by copreci­
pitation method showed higher density, strength and more bioactivity
for those compositions having a higher 70% HAp: 30%TCP content [65].
On the other hand, 20% HAp - 80%TCP and pure TCP did not show any
surface reactivity. The biological performance of Ca deficient Hap
(CDHA) with BCP is enhanced by adding alginate. The in-vitro and
in-vivo studies in intramuscular implantation, exhibited that CDHA with
a high content of BCP (20% HAp: 80%TCP) showed better osteoinduc­
tivity and bioactivity [66]. In summary, these finding indicate that the
resorbability and bioactivity of BCP ceramics can be controlled by
varying their β-TCP/HAp ratios.
2.4. Fabrication processes of bioceramics
Bioceramic manufacturing methods have steadily made progress over
the last 50 years. Different methods are used for the fabrication of bio­
glasses, but commonly used methods are melt quench and sol-gel (wet-
chemical) [50,67–74]. In the melt quench method, glasses are prepared
by melting a mixture with proper selection of a high purity stoichiometric
amount of various oxides or carbonate oxides at a high temperature [44].
Mixtures of raw materials in the form of powder are melted at high
temperature, i.e. > 1300 ◦ C, and rapidly quenched to freeze the atomic
structure [45]. In spite of most widely studied BG 455S, various other BGs
such as S53P4, A-W glass-ceramics with different compositions also
showed great interest in the melt quench method [42,43,46,75,76].
During melting, the temperature should be chosen so that homogenized
and bubble-free melt is obtained. The melting process may be performed
many times to reach an ultra-high level of homogeneity. The viscosity of
the melt can be < 100 P that provide bubble free melt [49]. The time
required for melting varies according to the size of the batches. Annealing
is performed on thermal treated glasses below the glass transition tem­
perature (Tg) that helps to eliminate of residual stresses produced during
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Ceramics International xxx (xxxx) xxx
the cooling process. While above Tg, the sintered glasses allow to form
porous architecture (scaffolds), draw of fibres, or form sealing particles
used for coating surfaces [77]. BG has also been used as a coating ma­
terial on biodegradable metallic implants to improve their bioactivity
and bio compatibility by using different fabrication methods [78,79].
Some key points that must be considered to select proper coating mate­
rials, since coating leads to poor sintering of biomaterials that retard the
properties of coated materials. Moreover, CTE must match of both the
materials to avoid fractures between implant and coating during sinter­
ing [78]. The properties of coating implants not only depend on the type
of material used, but also depend on the various processing methods as
shown in Fig. 2 [33,78,80,81].
A recent study showed that EPD is an appropriate method due to its
capability to control the coating thickness and can also attain homoge­
nous coating on complex shaped biomaterials [82]. On the other hand,
sol-gel method is also known as the wet chemical method. It requires a
low temperature (600–700 ◦ C) for oxides to make glasses. The sol-gel
method used composition range up to 90 mol% of SiO2, while for melt
derived BG maximum silica content is 60 wt%. Sol-gel method has
involved different synthesis steps to make BG powder, such as for
preparation of an inorganic matrix, mixing of the alkoxides in the so­
lutions, hydrolysis, gelation, and low temperature calcination. Studies
also indicate that sol-gel derived glasses have weak connectivity because
of the presence of a hydroxyl group that enhances the bioactivity of BG
[67,83]. A novel sol-gel method was used for borate-based glasses with
contents 36–61 mol % based on melt derived borate substituted for BG
4S5S used for wound healing applications [41,44,48].Various re­
searchers have also prepared borosilicate-based BG using sol-gel
method, containing a content ranging from 0.2 wt% to 53 wt% of
B2O3. Studies showed sol-gel method is an alternative choice for melt
quench method for producing porous bioglass/glass-ceramic scaffolds
[15,84]. In addition to above mentioned process methods, other fabri­
cation methods are also used to make scaffolds for tissue engineering
such as foam replica, sponge replica, sol-gel foaming, selective laser
sintering (SLS), stereolithography (SLA) and additive manufacturing or
3D printing, robocasting or direct ink writing [15,85–88].
Foam replica method can be used by dispersing a gas in the form of
bubbles into a ceramic suspension or colloidal sols, followed by solidi­
fication. This method helps in the fabrication of both closed and open
cell foams. In this method, solution can be cast in moulds and obtained
good versatility of final shapes without adding any machining. However,
it has drawback such as poor interconnectivity due to non-porous
external surfaces of the developed materials [86]. The Sponge replica
method is also an effective method for producing foam like ceramic
scaffolds for tissue engineering. This method is applicable to any
ceramic materials that can be dispersed into a suspension. Another key
point of this method is that the initial sponge can be easily cut and
confirmed to match the size and shape of the bone defects. Whereas, this
method is ineffective at achieving the required mechanical properties of
developed materials [87].
Sol gel foaming method involves the conversion of precursor (sol)
into a network of covalently bonded silica by polymerisation reactions.
The most important challenge is to develop uniform and evenly
distributed pores (size > 300 μm) with minimum porosity requirement
50 vol% for scaffold application [86]. It has been reported that sol-gel
method produces controlled particle size, pores (2–50 μm), easy syn­
thesis of thin films and coating on BG [89–92]. So, good processing
chemical route like sol-gel could be a good choice for synthetic scaffolds.
Additionally, during processing, some surfactants could be added to
increase the porosity of the final bio-ceramic materials. Besides many
advantages, this method also has some disadvantages, like formation of
nanosized BG without fractures is very difficult, for removal of organic
reactants is required high temperature [92,93]. Selective laser sintering
(SLS) is a method of forming 3D objects by sintering thin layers of
powdered ceramic materials using a CO2 laser beam. The laser beam is
scanned over the powder bed according to the computer-aided data,
S. Punj et al.
Fig. 2. HAp/bioglass used as coating material on metallic implants using different methods.
increasing the temperature of powders only in particular areas. Particles
fuse together in this manner, allowing successive layers to be formed
directly on the top of the already sintered material. Stereolithography
(SLA) is also a promising additive manufacturing method used to
fabricate tissue scaffolds. SLA method used to prepare 3D objects by
combination of ceramic powders and a photo-curing a liquid resin via
UV laser beam in a layer wise form. These methods are used to fabricate
of nano HAp, TCP and BCP, BG scaffolds [1,86,94].
Additive manufacturing or 3D printing (3DP) is a powder-based
method that uses a printer head which moves in order to object profile
produced by a computer system to eject and deposit binder onto the
powder surface, thereby bonding the granules in the selected regions. A
new layer of powder is then established by a set of rollers. The cycle is
repeated until the entire object is completed, at this point, an airflow is
used to eliminate any unconstrained powder. The objects are sintered at a
high temperature to achieve sufficient body strength and to safely
remove the binder (organic or water based). Different types of ceramic
materials for tissue engineering have been processed using 3D printing,
such as HAp, CaP, calcium sulphate, BG, and glass-ceramics [86,95–97].
3D printing can be used to produce macroporous structures of scaffolds.
However, due to print nozzle accuracy, 3D printing method is still a
challenge to produce gran size <10 μm. Robocasting or direct ink-writing
methods also belong to the class of 3D printing method. In this regard, BG
scaffolds with a regular arrangement of pores in 3D and extraordinarily
high mechanical performances in compression and flexure were pro­
posed for possible application in the substitution of cortical bone and
load-bearing segments of the skeleton as discussed in the next section.
2.5. Effect of modifiers and intermediate oxides on bioactive glasses/
glass-ceramics
BG proved to be an excellent material. However, it still has certain
drawbacks due to the presence of high alkali contents including: (i) fast
dissolution rate produces negative effect on bone remodulation that
causes formation of gap between implants and tissues (ii) due to higher
content of Na2O when released in culture medium increases the local pH,
causing cell death [42,98–100].(iii) BG (45S5) tends to crystallize at high
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Ceramics International xxx (xxxx) xxx
temperature due to presence of high silica content. Moreover, crystalli­
zation of BG reduces its bioactivity. (iv) difficult to fabricate highly
porous scaffolds due to its early crystallization and poor sinterability that
inhibits the densification, which causes poor mechanical strength [101].
Continuous research has been going on BG 45S5 in order to meet the
desired properties by overcoming some of its limitations. Many re­
searchers tailor the BG properties by adding or replacing the 45S5 BG
composition with modifiers and intermediate oxides as shown in Fig. 3.
Recent attempts to give an alternative to 4S5S BG by using K2O (7–13 mol
%) content in place of Na2O content formed fluorocanasite, cuspidine and
wollastonite crystalline phases that improved the bending strength from
110 ± 10 to 137 ± 7 MPa and fracture toughness 2.6 ± 0.1 MPa m1/2 of
glass-ceramics [76,79,91,102–105]. It was also reported that Na2O is not
an essential component for the degradation of the BGs [43,106,107].
Na2O free fluoride-based BG forms FAp in SBF, which is an important
component for tooth enamel and other dental applications, as it is much
more resistant to acidic conditions than HAp [106]. Addition of 2.5% Cu
concentration in BG also increase the cell volume obtained from XRD
results. It also revealed apatite precipitations with Ca/P ratio of 1.68 after
21 days of mineralization that were used for tissue engineering [75,108].
Among the investigated elements, other transition metal ions such as
combination of TiO2+ZrO2 (up to 1mol%) doped in 45S5 BG for SiO2
showed more pH value after soaking the sample in SBF which favours the
formation of dense HCA layer [109]. A recent study of Ti–45S5 based BG
modified with silver (Ag) found that Ag reduces the bacterial effect on the
glass in comparison to only Ti based BG 4S5S) [72]. In-vivo study also
showed niobium (2.6 mol %) containing 45S5 BG was capable of filling in
the critical-sized calvarial defect of animals in 8 weeks. Defects filled with
niobium-based glass showed over 90% coverage compared to just 66%
for 45S5 BG [110]. It has been found that with addition of Al2O3 or ZrO2
or high contents of CaO (up to 40 mol%) in CaO–MgO–SiO2–Na2O–Li2O
based bioglass/glass ceramic raises the sintering temperature, while
Na2O decrease the glass transition and sintering temperature. The addi­
tion of up to 12 mol% of MgO to glass helps in the formation of the
diopside phase, and 9 mol% of Na2O helps in formation of combeite
phase. These phases showed significant bioactivity (after 3 days) as well
as no cytoxicity in these glasses. The bending strength of 100 MPa
S. Punj et al.
Fig. 3. Effect of modifiers and intermediate oxides on 45S5 BG composition and their properties.
(residual porosity <10%) is used for bone graft implants [111]. NiO
(0–1.65 mol%) is also substituted for the BG, and glass-ceramics
(Na2CaSi3O9) are prepared using a melting and annealing method. Re­
sults showed that an increase in NiO contents, enhanced the density
(2.77–2.89 g/cm3 for BG and 2.91–2.95 g/cm3 for glass-ceramics),
compressive strength (68.92–82.13 MPa for BG and 113–121 MPa for
glass-ceramics), flexural strength (42.43 MPa–66.58 MPa for BG and
104–121 MPa for glass-ceramics), and microhardness (5.35–5.99 and
7.68 to 8.14 for glass-ceramics) [112]. From the above results, it can be
summarised that, the bioactive behaviour of the bioglasses also depends
on the base glass and the presence of crystalline phases and their volume
in the glass matrix.
On the other hand, bioceramics and BGs/glass-ceramics also have an
appealing property as a scaffold material used for bone healing and
regeneration [15,85–88]. A scaffold with 90% porosity and well inter­
linked pores with a diameter of 100–300 μm and compressive strength
should lie between 1 and 10 MPa that boost the bone growth in 3D
interlinked pores [113]. But high porosity causes a negative impact on
the mechanical properties, like fracture toughness. Studies show different
fabrication methods are also used for the formation of porous bio­
ceramics, bioglass/ceramic scaffolds without sacrificing its mechanical
properties, such as sponge replica, sol-gel foaming, selective laser sin­
tering (SLS), stereolithography (SLA) and additive manufacturing or 3D
printing, robocasting or direct ink writing [15,113,114]. A porous
ceramic scaffold was fabricated using a ceramic camphene-based co-ex­
trusion method. It shows high compressive strength (19.3 ± 2.7 MPa)
than random porous structure (0.280 ± 0.80 MPa) with 83% porosity
[115]. Recent studies reported that the addictive manufacturing or 3D
printing method has better capability to control the porosity of the
scaffolds than traditional methods [95]. CaP ceramic scaffold fabricated
into proper shape by controlling the pore size and material composition
of scaffolds, as well as tailoring the degradation rate of scaffolds, can be
successfully used to make various types of bone tissue implants and skull
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Ceramics International xxx (xxxx) xxx
bone tissue reconstruction using this 3D printing method [95].With this
method the mechanical properties of scaffolds also meet the re­
quirements of cancellous bones. The porous 3D printing CaP materials
were also crosslinked with sodium alginate. It was found that the
cross-linking effect was quite different when materials were formed with
different fabrication techniques. For instance, when material formed
with mould, the Young’s modulus of the material was 278.2 kPa. On the
other hand, when it is used with a 3D printing scaffold the value of
Young’s modulus is 1330 kPa. The compressive strength of the 3D
printing was observed 16.9 ± 1.5 MPa. The scaffold also showed anti­
bacterial properties loaded with berberine as well as bone regeneration
function used for jaw bone repair [96].These 3D printing scaffolds also
showed low cytoxicity that is beneficial to adhesion and proliferation of
MC3T3 cells [96]. Micro porosity (pore size < 10 μm) also plays an
important role in improving the osteoinduction of scaffolds. The high
specific area, surface roughness and surface energy of microporous
scaffolds have a more effect on the protein adsorption. Moreover, capil­
lary force produced by the micro porosity can enhance the cell attach­
ment on the scaffolds surface [116]. For instance, CaP within the range of
0.1 μm–10 μm have higher osteoinduction and osteogenic ability than
non-micropore analogues. Strontium (Sr) doped 3D HAp scaffolds are
also produced using a hydrothermal method which is used for osteopo­
rotic bone defects. The results exhibit that the release of Sr in aqueous
medium enhanced the early angiogenesis rate [117]. The micro/­
nanoscale pores in scaffolds (̴ 100–10,000 nm) were also obtained by a
hydrothermal method that helps to enhance metabolite transportation.
An in-vitro study showed that micro/nano whisker coating scaffolds with
natural wood hierarchical pores also exhibited good osteoinductive
property which were fabricated by combined 3D printing and hydro­
thermal methods [118]. For better osteogenesis, migration and cell
adhesion, the material’s Young’s modulus, shear modulus, toughness and
compressive strength should be matched to the bone. For instance,
SiO2–Na2O–K2O–MgO–CaO–P2O5 glass-ceramic scaffolds are fabricated
S. Punj et al. Ceramics International xxx (xxxx) xxx

by the robocast grid method [119]. The results showed great control on
inner porosity (49 vol%), a fracture toughness 93 kJ/m3, compressive
strength 6 MPa, Young’s modulus around 340 MPa (which is within the
range of compressive strength (2–12 MPa) and young’s modulus
(50–500 MPa) of cancellous bone) [120]. Similarly, silicate 13–93 BG
scaffolds fabricated by the same method showed grid like microstructure
with porosity 47% tested in (SBF) in-vitro as well as implanted in rat
subcutaneous model in-vivo. The results exhibited that the scaffold’s
strength was 86 ± 9 MPa, elastic moduli 13 ± 2 GPa and Weibull
modulus 12 during testing in compression. In flexural loading, strength
11± 3 MPa, elastic moduli 13 ± 2 GPa and Weibull modulus 6 and brittle
mechanical response in SBF modified to an elasto plastic response after
immersion for more than 2–4 weeks in-vivo [121]. The scaffolds also
designed using bioglass hybrids (PCL/SiO2–CaO) through sol-gel method,
which was highly flexible and effectively enhanced the fracture tough­
ness of the developed materials [122].
According to a literature survey, most of the studies focused on the
compressive strength and porosity of different bioglasses/glass-ceramics
scaffolds. The variations in compressive strength of the scaffolds greatly
depends on different glass compositions, foaming agents, sintering
temperature, density, interconnected pore size, and porosity, as listed in
Table 2. Higher densification can be obtained at higher temperature,
that also affects the mechanical properties. As an increase in density
reduces the pore size that increases the strength of scaffolds, but reduces
the bioactivity of bioglasses/glass-ceramics [123]. On the other hand,
compressive strength not only depends upon the porosity but also on the
different pore geometries (spherical, cubic, diamond, gyroid, x, rectan­
gular, honey comb, hexagonal) of bioglasses/glass-ceramics scaffolds, as
shown in Fig. 4.
In a recent study, the borate based bioglass scaffolds were prepared
via SLS method to study mechanical properties using pore sizes (0.5–1.2
μm) and compressive strength varying from 1.7 to 15.5 MPa, corre­
sponding to porosity varying from 60 to 30%. The in-vivo results
exhibited that the defects treated with the diamond shape scaffolds had
more fibrous tissue generation and thus had the ability to fast bone
formation [94].
Bioglass (1 wt %) added to calcium silicate ceramic (sintered at
1000–1150 ◦ C) using a direct ink writing method to study the effect of
different pore morphologies (rectangular, honey comb, parallelogram) of
scaffolds on mechanical properties. The results showed a compressive
strength of 48 MPa (rectangular) < 88 MPa (honey comb) with ~60%
porosity. This novel approach could be a better choice to balance pore
structure and sintering activity towards preparing high-strength bio­
glass/ceramic scaffolds [125]. The same method was also applied to
fabricate a 3D scaffold with hexagonal geometry providing compressive
strength lie in the range of cortical bone (100–150 MPa) and fracture
toughness of 30 MPa, used to repair large bone defects [126]. Another
new generation of bioactive glasses referred to as mesoporous glasses
(MBGs) ranging (2–50 μm) fabricated by incorporation of supramolecu­
lar chemistry of surfactants to sol-gel process [127]. MBGs possess a
similar composition to traditional bioglass (SiO2–CaO–P2O5) have shown
great attention due to their significant features of a highly ordered
structure, tuneable nanopores (5–20 nm) and a specific surface area
[127]. In addition, different mesotructures (like 3D structure, rods or
sheets) can be attained by varying the amount of surfactant that act as
structure directing mesophase template [128]. The MBGs are used to load
and control the release of a large number of drugs, promote the prolif­
eration of cells, osteogenic differentiation, wound healing and bone
repair applications. Studies have exhibited that MBG doped with thera­
peutic elements (Si, Mg–Ca–Si, Sr, Ag, Cu, Zn, Ce, Ga, Fe etc.) in suitable
amounts show a higher degradation rate, in-vitro bioactivity, in-vivo bone
formation and antibacterial properties in comparison to non MBGs
[129–134]. Recent research has reported that MBG is also fabricated in
the form of nanoparticles to improve the stability, injectability, textural
properties and surface area to enhance their drug carrying capacity and
combined osteogenic-angiogenic potential in comparison to micron sized
MBG [135,136]. MBGs nanoparticles of an average size 120 ± 10 nm
were also used to load and release silibinin, which act as a tumour sup­
presser and anticancer agent for the treatment of breast cancer [137].
MBGs nanoparticles can also be used as nanovehicals for co-delivery of
Ag, Cu ions and tetracycline to repair infected bone and dentin pulp [132,
138]. Some studies also show that MBGs can be applied as a coating on
various types of foam-like structures to obtain multifunctional systems
with enhanced compressive strength, Young’s modulus and hardness but
less improved fracture toughness [134,139]. In addition, 3D scaffolds
also show enhanced mechanical properties when these are synthesized
with a matrix of biopolymers to form nanocomposites [140]. It can be
concluded from above studies that the changes in basic BG 45S5
composition and processing methods effects the structural, mechanical,
and bioactive properties. Regarding this feature, there are also other

Table 2
Compressive strength and porosity of different bioglasses/glass-ceramic scaffolds depends on different factors sinterability, density and interconnected pore size.
Composition of bioglass/glass ceramic Methods Sinter Density Inter connected Porosity Compressive Reference
scaffolds temperature (g/cc) Pore size (%) strength (MPa)

45S5 BG Powder and polymer 975 ◦ C 250 μm 64–79 13.8± [88]

foaming 2.4
45S5 BG Gel casting with foaming 850 ◦ C 0.45± 100–500 μm 70 1.22 ± 0.7 [124]
agent (0.1–0.3) 0.04
0.37± 86 0.78 ± 0.4
0.08
60SiO2-37.5CaO- 2.5 P2O5 based BG Sol-gel 700 ◦ C 70 30 3.3 [88]
Na based BG 55 46 1.2
Borosilicate based BG Foaming agent (using 540 ◦ C 250–570 μm >50 1.29 ± 0.21 [85]
Borophosphate based BG 60–70% NH4 (HCO3) 1.56 ± 0.63
Phosphate strontium-based BG 500 C ◦
3.63 ± 0.69
CaSiO3–CaMgSi2O6 scaffolds (air) Direct ink writing 1100 ◦ C 1.00± 68 4.9 ± 0.7 [123]
0.08
CaSiO3–CaMgSi2O6 scaffolds (nitrogen) 0.76± 76 3.9 ± 0.5
0.05
CaSiO3–CaMgSi2O6 scaffolds 1.04± 67 7.7 ± 0.4
0.07
49.46-SiO2, 36.6-CaO-6.6-Na2O-1.07-P2O5- Gel casting 690 100–150 μm 75 3.4 ± 0.3 [87]
6.6-K2O mol%
54.6-SiO2-22.4 CaO–6Na2O-1.7 P2O5-7.9- 700 8.4 ± 0.8
K2O, 7.7MgO mol%
Phosphorous strontium-based BG 690 15.3 ± 1.8
SiO2–Na2O–K2O–MgO–CaO–P2O5 Robocast grid 49 6
Bioglass ceramic Stereolithographic 700-400 μm 60 3.5 to 6.7 [86]

8
S. Punj et al.
Fig. 4. Relationship between compressive strength and pore geometries of different bioglass/glass-ceramic scaffolds.
important parameters such dissolution rate, in-vitro testing, biocompati­
bility and antibacterial properties of BG also add different dimensions to
the utilization of these BG as discussed in the next section. Thus, BG has a
very high potential to act as good bioactive materials since it allows easy
accommodation of different additives and optimizes the properties ac­
cording to the need and application by selecting the proper processing
and initial ingredients of the glasses.
3. Important parameters for bioactivity
3.1. Dissolution behaviour of bioglasses
Dissolution rate plays an important role for bioactivity. It also gives
information of apatite formation due to biomineralization of glass is
dependent on the glass dissolving in the body fluid and the release of
Ca–P ions [50]. Dissolution rate should be compatible with rate of bone
formation. If the dissolution rate is too low, the ionic concentrations are
inappropriate to promote cellular proliferation and differentiations. On
other side, if the dissolution rate is too fast, the ionic concentration may
be higher than the effective level. The rate of dissolution and ion release
in glass are affected by the glass network structure and type of ions
present in the glass. Highly polymerized glass networks dissolve slowly,
vice-versa [41]. Some studies show no correlation between network
connectivity and dissolution behaviour. The results exhibited that the
dissolution behaviour was affected by the presence of ionic species in the
glass. It includes valence and ionic radii that examine their leaching
behaviour [141]. The dissolution rate and connectivity of the glass
network could be tailored by adjusting the composition and fabrication
techniques of glass. For instance, when the contents of silica are high
results in a highly interconnected system in which bridging oxygen atoms
serve as a network stabilizer during dissolution, resulting in lower
bioactivity in melt derived glasses. The presence of modifiers cations has
been shown to be an efficient way for increasing the bioactivity of melt
derived glasses. NC represents the network connectivity of melt derived
glasses, which is typically described as Qn, where Q refers to the different
structures that can describe network connectivity in a silica-based glass.
It is proportional to the average number of bridging oxygen atoms (n) per
silicon and can range between 0 and 4 [142]. It was found that the NC
increases as the bioactivity of the glass decreases. The 45S5 BG value was
found to be about 1.9 [39]. If the value > 2.6 the system is not to be
considered bioactive [41]. On the other hand, in sol-gel method, the
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Ceramics International xxx (xxxx) xxx
higher concentration of silica (up to 90 mol %) can be considered due to
two factors: textural nano-porosity, that gives a higher surface area to
volume ratio and the action of H+ ions, that serve as network modifiers
by depolymerize the silica network [84]. Various methods are used to
determine the atomic structure of amorphous systems, magic angle
spinning solid-state, Nuclear Magnetic Resonance (NMR) measuring the
relative percentages of Q structures in the glass. Several research studies,
are also based on statistical mechanics for the modelling of distribution,
including computational dynamic modelling, synchrotron-based XRD,
and neutron diffraction (ND), are also widely used especially combined
with solid-state NMR, Raman spectroscopy, Fourier transform infrared
(FTIR) spectroscopy, and computational modelling [143].
3.2. In-vitro bioactivity testing
In-vitro testing is used as a safety tool before real testing of materials
in in-vivo. Various methods have been established with regard to media
types that affect the bioactivity of biomaterials such as SBF, Tris buffer,
Dulbecco modified eagle medium (DMEM) and saline solutions such as
phosphate buffered saline (PBS), NaCl, K2HPO4, etc. In spite of this,
different important immersion conditions, such as surface to volume
ratio, static or dynamic arrangements, geometry of test samples, are also
major factors to validate the in-vitro testing is summarised in Table 3. In
1991, Kokubo and his colleagues formed SBF, whose ionic concentration
resemble the inorganic parts of human blood plasma. Later on, different
types of SBF were also proposed to check the in-vitro bioactivity of the
materials. But Kokubo protocol is still widely used to check the bioac­
tivity of materials [144–147,153]. Tris buffered SBF has also been
recently recommended unified method by the members of the Interna­
tional Commission on Glass (ICG) particularly to those glasses having a
high surface area and particle size maximum 90 μm and surface to
volume ratio 75 mg in 50 ml [154]. Various studies recently also re­
ported for different solutions used for in-vitro degradation of bioactive
glasses/glass ceramics combined with polymeric and composites-based
biomaterials for various compositions [46,148,149,155,156]. PBS was
also used to study the in-vitro effect on BG containing polymeric mate­
rials (hydrogel composites, polyurethane/58S) [149,157]. K2PHO4 so­
lution testing showed a faster speed of HAp formation in comparison to
SBF for B2O3 (up to 30%) doped 45S5 glasses. On the other hand, when
SBF solution was refreshed every day, formation of fastest HAp for low
concentration of boron (<30%) samples and no significant difference
S. Punj et al. Ceramics International xxx (xxxx) xxx

Table 3
Parameters and test methods that have been used to investigate the bioactivity of different bioglass/glass-ceramics based compositions derived from conventional
source.
Composition Medium Geometry Surface area to Conditions Days Remarks References
volume ratio

55SiO2–40CaO-(5-x) SrO-xAg2O, (x = 0,2, SBF Glass Static 7–14 days Formation of HAp [144]
mol %) after 7 days
85SiO2-(15-x) CaO–MgO, with x = 1, 3, 5 SBF Glass powder 2 mg Stirring (120 1,3,7,14 Poorly crystallized [145]
and 10 mol%) /ml rpm) days HAp on 14 day
B2O3(0.5–15mol%) doped in 80% SBF Glass 1 mg Static 10 min to 7 Formation of HCA [146]
SiO2–15%CaO-5% P2O5 /ml days within few hours
SiO2–CaO–Na2O–SrO–Ag2O–P2O5 SBF Glass powder 0.1 g/45 ml Static 21 days Formation of HCA [147]
after 14 days
46.1SiO2-2.6P2O5-26.9CaO-24.4- Na2O; in Tris buffer with Glass powder <38 75 mg Stirring (60 1,3,7 days Apatite layer formed [148]
mol% acetic acid μm /50 ml rpm) after 7 days
SiO2–P2O5–CaO–CaF2 with 0–4.5 mol% Tris buffer Glass powder 75 mg/50 ml Stirring (60 1–168 h Apatite formed in first [46]
CaF2 rpm) 3h
Ga-containing BGs and hydrogel polymeric PBS Bioglass Particles Static 1, 7 & 30 Antimicrobial and [149]
composites days antifungal
BHA/glass-Sr composites 0.9% NaCl 2.5 mg and 11 mm Solid/liquid Static 2,5,7 days Decrease HAp layer [150]
diameter disc 1:30
B2O3(30mol%) doped 45S5 K2HPO4 Glass 0.02mol Static 10 days HAp formed in 7 days [151]
/L
SiO2 38.5-CaO 36.1-P2O5 -5.6-MgO-15.2- DMEM Bulk sample, Thin 0.5 cm2 Static 28 days Formation of HAp [152]
ZnO and CaF2 0.6 film, powder /ml

was observed for K2HPO4 solution [151]. Apart from SBF, Tris buffer
and saline solutions, DMEM medium is used to study the bioactivity as
well as biocompatibility of the material. It has been recently reported
that when DMEM is used with protein, i.e. foetal bovine serum (10%) to
check the in-vitro bioactivity of glass films, showed more suitable results
than SBF [152].
3.3. Cell culture test for biocompatibility
In the biomedical field, cultivated human and animal cells have been
used for many decades to test the biocompatibility of developing mate­
rials. In cell culture studies, various cell lines and assays are used to
identify the biological effects of chemicals and drugs. Various cytoxicity
and cell viability assays depend on different cell functions, such as cell
adherence, ATP production and enzyme activities, etc. Cytoxicity assays
are classified into various assays such as dye exclusion assays, colori­
metric assays, fluorometric assays and luminometric assays [158]. The
selection of particular assay is essential to obtaining reliable and accurate
results. Cell lines or tissues also affect the performance of the cytoxicity or
cell viability assay [158,159]. Among these assays, the current study is
mainly focused on colorimetric assays such as lactate dehydrogenase
(LDH),3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetra zolium bromide
(MTT), 3-(4,5-dimethylthiazol-2-yl) 5 (3carboxymethoxyphenyl)- 2
-(4-sulfophenyl)-2H-tetrazolium (MTS), etc. that are widely used to
investigate the cellular viability and cytoxicity of the bio glasses as listed
in Table 4 [160–165]. These calorimetric assays are based on the mito­
chondrial activity of the cells, that is correlated with cell viability. There
are several studies based on colorimetric assays that demonstrate that
due to the addition of different dopants such as Sr, Zn and Co still showed
some risk of toxicity. While, when the concentration of doping elements
is low, showed less toxic in comparison to a high concentration of ele­
ments [160,162,164,165]. Some studies reported, prior to cell culture
test, BG treated with pre-conditioning treatments and others were treated
without pre-conditioning treatments. The pre-conditioning of BG in SBF
or DMEM leads to more biocompatible for cell culture [166]. This
pre-conditioning treatment used to stabilise the rate of release of ions,
because more release of ions showed a negative effect on cell viability.
The duration of the pre-conditioning treatment depends upon the

Table 4
Different cell culture, cell lines and assays used to assess the biocompatibility of BG.
Material/composition Evaluation Cell culture Cell lines Assay Incubation Results Reference
(medium) period

Silicate, phosphate and borate Cytoxicity checked for all DMEM rat calvaria MTT 1–7 days Cytotoxicity could be [167]
glass compositions glasses (0.1–10 mg/ml) osteoblast cells observed across all of the
containing different oxides glasses.
Pre-conditioning of 45S5 BG Impact of passivation With and without Human bone 72 h Cell viability is higher for [161]
period on BG for (1,2.5 and passive tion of marrow derived 72 h than 24 h passivated
5 mg/ml) DMEM MCSC BGs.
Sr and cobalt containing BGs Cell cytoxicity, ALP, (4 DMEM induced MTT 1,5,7 days Viability on day 1 was [162]
mg/ml) pluripotent stem 73% and on 7day become
cells 63%
Li and Sr substituted for Ca in Cell proliferation, ALP α-MEM MC3T3-E1 MTT 1,3,7 days Enhance cell growth and [163]
58S BG (1,5,10 mol%) ALP activity
HA-SiO2-GIC Cytoxicity effect (3.1–200 DPSC MTT All con-centration’s [164]
mg/ml) showed cytoxicity effect
HA-Au nanoparticles Compared MTS and LDH Human MCSC MTS, MTS showed good [165]
results for (1–100 μg/ml) LDH viability in comparison
assay to LDH

HUVE: human umbilical vein endothelial cell line, RTCA: RCELL igencereal time cell analysis, ALP: Alkaline phosphatase, DPSC: dental pulp stem cells, MCSC: mesne
chymal stromal cell.

10
S. Punj et al.
composition and morphology of the samples. Results indicate that bulk or
particle type materials required short duration for pre-treatment in
comparison to porous.
materials due to fast exchange of ions in the solution [98]. Melt derived
BG (49.46 SiO2-36.6 CaO-1.07 P2O5-6.6K2O mol%) with 75% porosity
pre-treated with serum free DMEM, penicillin and streptomycin for 48 h,
tested on a human osteoblast cell line (MG-63) and mouse osteoblastic
(MC3T3-E1) cells using MTS and almar blue assays, showed good viability
[87,168]. BG with composition 46.1SiO2-28.7CaO-8.8MgO-6.2P2O5-5.7­
CaF-4.5Na2O of particle size 56 μm also showed good osteogenic differ­
entiation and higher biocompatibility in comparison to 45S5 BG using
preconditioning of the BG in cell culture medium for 24 h [43]. In recent
studies, also synthesized a novel pH neutral calcium phosphosilicate BG
that does not require pre-conditioning treatment prior to the cell culture
test. Similarly, the glass (54.2SiO2–35CaO-10.8P2O5 mol %) was synthe­
sized using a sol-gel method and its biocompatibility was tested using
preosteoblast cell lines (MC3T3-E1) without pre-soaking treatment. The
results showed good cell proliferation and dissolution test showed stable
pH due to the presence of higher phosphorous contents than 45S5 BG. On
the other hand, P2O5 free Ce doped BG biocompatibility test was per­
formed on MLO-Y4 cell lines (Murine long bone osteocyte-Y4) with DMEM
medium. The results of both direct and indirect test showed excellent
viability as well as cell proliferation after 24 h and 72 h without damage to
the morphology [169].
3.4. Antibacterial properties of bioglasses/glass-ceramics
In recent years, there has been increasing interest in the potential
antibacterial properties of BG. Antibacterial properties are very sensitive
to the composition, morphology, dissolution behaviour, particle size
and surface area of the glasses [170]. BG should contain elements in
its composition that have good antibacterial properties to prevent
post-surgery infections [171]. The particle size of BG should be small can
have large impact on the antibacterial efficiency of the material because
smaller particle size increases the active surface area and consequently
enhances the release of ions from the glass. The release of their ionic
compounds over time in an aqueous solution results in a high pH envi­
ronment, capable of killing microbes [74]. Furthermore, the release of Si
has also affected the antibacterial activity of BG. An in-vitro studies re­
ported that BG when introducing with divalent cations Mg, Cu, Sr, Ag, Zn
shows strong antimicrobial effects for a wide selection of direct culture
and indirect culture methodology, due to the increase of pH and osmo­
larity in the local environment [74,170–172]. Li and Sr substituted for Ca
in 58S BG had the highest antibacterial activity against methicillin resis­
tant staphylococcus aureus bacteria (MRSA) [163]. Borate-based glasses
by introducing Ti (0–15 mol%), Ti alloys, were also inhibited the micro­
bial infection against Streptococcus mutans and supressed biofilm for­
mation [170,173].The morphology of the BG is also an essential parameter
which plays an important role in the antimicrobial properties of BG.
Gamma-irradiated BG 45S5 having a homogenous spherical shape and
size occurring in the nanometre range (<50 nm) showed good results
against E. coli, S. aureus and multi drug resistance bacteria [124]. The
results demonstrate that with pH rise, the microbial counts decreased.
SEM results also confirmed the shrinkage of the cells and damage to the
membrane after exposure of glass to irradiation. Alkaline pH and medium
SBF with gamma irradiation are considered most favourable conditions for
antimicrobial activity as well as ability to eliminate the biofilm produced
by Pseudomonas aeruginosa (P. aeruginosa) [174]. MBGs (70SiO2-(26-x)
CaO–4P2O5-xZnO (x = 0, 3 and 5 mol%) prepared by the combined sol-gel
process and polymer templating methods. Their antibacterial properties
were studied against Bacillus subtilis (B. subtilis) and P. aeruginosa. The
higher antibacterial inhibition (91.3%) was obtained by the 5 mol% ZnO
doped MBGs for B. subtilis, as well as 89.4% inhibition for P. aeruginosa
[67]. 1 mol% AgO2 doped MBG also showed 99% killing efficiency against
E. coli and S. aureus [138]. CaP, on the other hand, has very good
biocompatibility despite having poor antibacterial activity. Studies
11
Ceramics International xxx (xxxx) xxx
exhibited that CaP products can be affected by the presence of different
bacterial infections that cause serious problems. A recent study using a wet
chemical method prepared a silver (Ag) doped (1–5 wt%) CaP mask
filtration material. The results exhibited that Ag–CaP mask has shown
maximum efficiency 96% that can effectively filter the staphylococcus
aureus aerosol particles in the environment [175]. It can be concluded
from the above studies that the promising factors of BG/glass ceramics
have been underlining how their efficacy is related to the size or compo­
sition of antimicrobial agents capable of inhibiting the bacteria growth.
4. Agro-food waste derived bioglasses/glass ceramics
Ceramic biomaterials derived from agro-food waste/ashes have
various advantages over synthetic ceramic biomaterials, such as mini­
mal tissue rejections, good biocompatibility and biodegradability. The
agro wastes are renewable that reduce the fabrication and processing
cost of the biomaterial used for various biomedical applications. In this
framework, RH, SCB, CH, CC and their ashes are used to synthesize
biogenic silica nanoparticles (BSNP) that have received much attention
because of their biological properties helpful in different biomedical
applications, such as protein adsorption and separation, gene therapy,
drug delivery, scaffolds, medicine applications and biosensors [176,
177]. The particle size, morphology of BSNP controlled using different
chemical, thermal and microbial methods [178–180]. The most com­
mon technique used to prepare BSNP from CC via sol-gel method due to
have a unique spherical shape with a narrow size distribution that is
used for dental applications [181]. In parallel to this, a new approach
has also been utilised by biosynthesis methods, which is an alternative to
chemical methods as listed in Table 5.
These methods are non-toxic, cheap and environment friendly due to
the usage of agro wastes as a substrate for performing reactions to obtain
valuable products [93,183–185]. The biocompatibility of BSNP derived
from RHA, SCB was studied on the human lung fibroblast using different
concentrations of BSNP (0, 25, 50, 100, 200, and 400 mg/mL) for 24 and
48 h, results indicated no adverse effect on cell viability and morphology
up to 200 mg/mL [186]. The results suggested that BSNP is biocom­
patible and can be used as the best alternative of commercial silica [16].
On the other hand, the agro wastes/ashes are combined with synthetic
minerals to form bioglasses/glass-ceramics, as discussed in next section.
4.1. Agro wastes
RHA is an alternative low-cost and abundant silica precursor that
was used during the fabrication of the glasses. Different BGs synthe­
sized using Si from RHA and studied for in-vitro bioactivity, such as
46S6 glass, BG 45S5 doped with Sr and molybdenum (MoO3), have
shown better bioactivity and viability in comparison to obtaining it
from commercial silica [187–189]. Similarly, RHA based 45S5 glass
converted into glass-ceramics after heat treatment ranging from 900 to
1050 ◦ C for 2 h (h). The results showed a significant effect on the
mechanical (6.96% porosity and microhardness value of 364 HV),
physical (density 2.27 g/cm3) and biological properties (formation of
HAp after 7days of soaking in SBF) of these glasses in comparison to
commercial silica based BG [190]. MBG has also prepared from RHA
via sol-gel method for anticancer drug delivery and bone regeneration.
The results showed no cytotoxicity in normal cells and MBG-folic acid
with calprotectin (a water-insoluble anticancer drug) that kill the
cancer cells efficiently [191,192]. SCBA also used as a raw material to
prepare glass and glass-ceramics (wollastonite) as a replacement of
silica which is used as a coating material. The SEM results showed
microporous network of elongated crystals with some areas with
dendritic, feather-like ordering, which crystallized at 1050 ◦ C. Vickers
microhardness value was 564.4 HV [193,194].
4.1.1. Food wastes
ESP was utilised to replace the synthetic CaO that is being used to
form βTCP, HAp, BCP, CaO nanoparticles by using different processing
S. Punj et al.
Table 5
Biogenic nano-silica produced using different fabrication method.
BSNP fabrication method Substrate Particle size Morphology
Sinteritation RHA – Spherical
Hydrothermal method RHA 10 μm Cubical
Sol-gel CC 50 nm
Extraction and precipitation SCB 30–500 nm Spherical
Biotransformation (microbial CC 40–70 nm Spherical
method)
Biotransformation (microbial RH 400 nm Pyramid cubical spherical
method) 85 nm (3 nm and 24 ± 8 form
nm)
methods [195–198]. The obtained results have shown that the ESP
derived CaO exhibited a macroporous structure, while HAP biomaterial
showed a nanocrystalline structure with size ranging from 50 to 100 nm
[199]. ESP was also utilised to synthesize akermanite (Ca2MgSi2O7),
diopside (CaMgSi2O6) phases via sol-gel combustion method and me­
chanical milling method [200]. The results indicated the HAp formed
(Ca2MgSi2O7) after 7 days of soaking in SBF, which helps in promoting
cell proliferation, osteogenesis, angiogenesis and suppress osteoporotic
bone regeneration when studied for an in-vitro test [201]. On the other
hand, CaMgSi2O6 phase results exhibit that the increasing temperature
from 900 ◦ C to 1200 ◦ C with a holding time of 3 h, showed good thermal
stability. The bonding strength of this bioceramics was about 350 ± 7
MPa and had an excellent fracture toughness of 4 ± 0.3 MPa [202]. In an
in-vivo investigation, nanocoating of Cu-doped BGs (uniform thickness
40–50 nm) were prepared using egg shell membrane (ESM) indicated
better angiogenesis rate and better antibacterial activity than conven­
tional BG [203]. On the other hand, banana peel powder (BPP) showed
antioxidant, antimicrobial behaviour against bacteria and fungi used for
wound healing applications. In spite of this, BPP also provides other
health benefits like reducing blood sugar, lowering cholesterol,
anti-angiogenic activity, and a neuroprotective effect [204].
4.1.2. RHA with ESP
Recent studies used a combination of RHA and ESP with synthetic
minerals such as Na2O, MgO for fabrication of BGs and β-wollastonite
ceramics (850 ◦ C) by using melt quench and sol-gel techniques. These
glasses showed a rapid pH change, good bioactivity and formed globular
shape HCA layer after soaking in SBF for 14 days [195,205]. The degra­
dation and in-vitro bioactivity behaviour of waste-derived β-wollastonite
and the test reveal that the material shows excellent bioactivity with lower
degradation rates [206]. Similarly, addition of Mg and Al up to 1 wt% in
biogenic silica derived from RHA showed no negative effect on bioactivity
and biodegradability of glasses after soaking in Tris buffer [207].
5. Conclusion and future prospective
According to the studies cited above, ceramic biomaterials are being
used for various biomedical applications. The coating of bioactive
ceramic materials on metallic biomaterials further reduces their degra­
dation, wear and tear of implants. The composition, thickness and uni­
formity of the coating materials play very important role to form the
interface between implants and coating materials that lead long life of
the implants. Poor compressive strength of these materials could be
increased by the formation of the uniform pores and their symmetrical
distribution for scaffolds application using fine chemical route like sol-
gel, using some surfactants to achieve uniform distributed pores and
porosity. Complex porous structure with controlled degradation rate
could be obtained by additive manufacturing or 3D printing. Different
composite materials could be future biomaterials due to easy modifi­
cation in their properties by proper selection of blended materials. HAp
and diopside crystalline phase embedded bioactive glass matrix could be
good choice for bone graft and tissue engineering application. The rate
12
Ceramics International xxx (xxxx) xxx
Remarks References
Particles are uniformly arranged in a whole [178]
preparation
Formation of highly crystalline silica particles [180]
formation of amorphous silica [182]
Amorphous form of particles [161]
Reaction time took 7 days [181]
Reaction time took 11 days [164]
of degradation of the individual phase is distinct and does not match the
rate of new tissue regeneration that may result in the loss of mechanical
properties of selected biomaterials. In the ideal case, both phases should
be degraded at the same rate that is appropriate for the required ap­
plications. Ceramic materials and silicate based bioactive glasses are
very suitable for regeneration of bones, and coating materials on various
biomaterials. Bioactivity of materials highly depend on their processing
parameters and initial selection of composition. Therefore, selection of
initial materials and their need-based processing play very vital role to
fabricate desired biomaterials for human body application. To obtain
good mechanical and bioactive properties of material should have high
surface area with low grain size, lightweight and corrosion resistive in
nature. Lightweight elements with organic framework and structurally
nanocrystalline materials could be future biomaterials. Toxicity of ma­
terials is a very vital parameter for biocompatible materials. It is very
sensitive to process parameters, amount, structure, chemical and phys­
ical nature of the selected materials. Cell viability and antibacterial
properties of bioglasses are promising one and further modified by se­
lection of proper processing parameters and initial compositions of the
glasses. Different agro-food wastes containing same active minerals as a
synthetic mineral also used to make bioglasses/glass ceramics that is a
good choice for orthopaedics applications, since most of the biological
and mechanical properties of these materials are comparable to the
bone. However, poor control, on the final composition of agro-food
wastes derived biomaterials, is demerit of these sustainable resources.
Composite, mesoporous and nanocrystalline glasses, ceramic coated
materials could be future biomaterials. However, still lot of advance­
ment in process technology, selection of an appropriate materials, pri­
mary assessment of their structural, thermal, corrosive and bioactivity
properties are required. According to need and application, the devel­
opment of biomaterials is required highly and field specific expertise. In
other words, this field is highly interdisciplinary in nature, so, expert of
various science, biology, engineering, technology and medical fields
should come close to achieve the goal. Before in-vitro and in-vivo test of
the developed materials, in-silico test could be beneficial. It can not only
save the time but also give more insight about the bio materials.
Declaration of competing interest
The authors declare the following financial interests which may be
considered as potential competing interests: The present work is sup­
ported financially by department of science and technology (DST),
under the scheme of Women scientist scheme-A (WOS-A) under the
award-letter number SR/WOS-A/PM-23/2018(G)
Acknowledgement
The present work is supported financially by department of science
and technology (DST), under the scheme of Women scientist scheme-A
(WOS-A) under the award-letter number SR/WOS-A/PM-23/2018(G).
S. Punj et al. Ceramics International xxx (xxxx) xxx

References [33] D. Hashim, N. Cionca, D.S. Courvoisier, A. Mombelli, A systematic review of the
clinical survival of zirconia implants, Clin. Oral Invest. 20 (7) (2016) 1403–1417.
[34] A. Khaskhoussi, L. Calabrese, J. Bouaziz, E. Proverbio, Effect of TiO2 addition on
[1] S. Pina, R. Rebelo, V.M. Correlo, J.M. Oliveira, R.L. Reis, Bioceramics for
microstructure of zirconia/alumina sintered ceramics, Ceram. Int. 43 (13) (2017)
osteochondral tissue engineering and regeneration, Adv. Exp. Med. Biol. 1058
10392–10402.
(2018) 53–75.
[35] N.R. Patel, P.P. Gohil, A review on biomaterials: scope, applications & human
[2] M.M. Subedi, Ceramics and its importance, Himal. Geol. 4 (2013) 80–82.
anatomy significance, Int. J. Emerg. Technol. Adv. Eng. 2 (4) (2012) 91–101.
[3] J. Chevalier, L. Gremillard, Ceramics for medical applications: a picture for the
[36] J. Wang, Y. Cheng, L. Chen, T. Zhu, K. Ye, C. Jia, H. Wang, M. Zhu, C. Fan, X. Mo,
next 20 years, J. Eur. Ceram. Soc. 29 (7) (2009) 1245–1255.
In vitro and in vivo studies of electroactive reduced graphene oxide-modified
[4] Z. Abbasi, M. Bahrololoom, M. Shariat, R. Bagheri, Bioactive glasses in dentistry:
nanofiber scaffolds for peripheral nerve regeneration, Acta Biomater. 84 (2019)
a review, J. Dent. Biomater. 2 (1) (2015) 1–9.
98–113.
[5] W. Rieger, Ceramics in Orthopedics-30 Years of Evolution and Experience, World
[37] [a] C. Piconi, Bioinert ceramics: state-of-the-art, key engineering materials,
Tribology Forum in Arthroplasty, Hans Huber Verlag Bern, Suisse, 2001,
Trans Tech Publ (2017) 3–13;
pp. 283–294.
[b] L.L. Hench, R.J. Splinter, W. Allen, T. Greenlee, Bonding mechanisms at the
[6] M. Kaur, K. Singh, Review on titanium and titanium based alloys as biomaterials
interface of ceramic prosthetic materials, J. Biomed. Mater. Res. Part B. 5 (6)
for orthopedic applications, Mater. Sci. Eng. C 109 (2019) 844–862.
(1971) 117–141.
[7] P. Kurinjinathan, K.T. Arul, J.R. Ramya, Cobalt ions doped bioactive ceramics for
[38] L.L. Hench, I.D. Xynos, J.M. Polak, Bioactive glasses for in situ tissue
biosensor biomedical applications, Int. J. Cur. Res. Rev. 10 (21) (2018) 49.
regeneration, J. Biomater. Sci. Polym. Ed. 15 (4) (2004) 543–562.
[8] A. Ravaglioli, A. Krajewski, Bioceramics: Materials⋅ Properties Applications,
[39] J.R.J.A.b. Jones, Reprint of: review of bioactive glass, From Hench to hybrids 23
Springer Science & Business Media1992.
(2015) S53–S82.
[9] H.E. Jazayeri, M. Rodriguez-Romero, M. Razavi, M. Tahriri, K. Ganjawalla,
[40] L.L. Hench, I.D. Xynos, J.M. Polak, Bioactive glasses for in situ tissue
M. Rasoulianboroujeni, M.H. Malekoshoaraie, K. Khoshroo, L. Tayebi, The cross-
regeneration, Journal of Biomaterials Science, J. Biomater. Sci. Polym. Ed. 15 (4)
disciplinary emergence of 3D printed bioceramic scaffolds in orthopedic
(2004) 543–562.
bioengineering, Ceram. Int. 44 (1) (2018) 1–9.
[41] J.R. Jones, D.S. Brauer, L. Hupa, D.C. Greenspan, Bioglass and bioactive glasses
[10] K. Shanmugam, R. Sahadevan, Bioceramics-an introductory overview,
and their impact on healthcare, Int. J. Appl. Glass Sci. 7 (4) (2016) 423–434.
fundamental biomaterials, Ceram. Int. (2018) 1–46.
[42] A.F. Brito, B. Antunes, F. dos Santos, H.R. Fernandes, J.M. Ferreira, Osteogenic
[11] S. Balasubramanian, B. Gurumurthy, A. Balasubramanian, Biomedical
capacity of alkali-free bioactive glasses. In-vitro studies, J. Biomed. Mater. Res. B
applications of ceramic nanomaterials: a review, Int. J. Pharma Sci. Res. 8 (12)
Appl. Biomater. 105 (8) (2017) 2360–2365.
(2017) 4950–4959.
[43] S. Schmitz, B. Widholz, C. Essers, M. Becker, D. Tulyaganov, A. Moghaddam, I.
[12] B. McEntire, B.S. Bal, M. Rahaman, J. Chevalier, G. Pezzotti, Ceramics and
G. de Juan, F. Westhauser, Superior biocompatibility and comparable
ceramic coatings in orthopaedics, J. Eur. Ceram. Soc. 35 (16) (2015) 4327–4369.
osteoinductive properties: sodium-reduced fluoride-containing bioactive glass
[13] S.S. Danewalia, K. Singh, Bioactive glasses and glass-ceramics for hyperthermia
belonging to the CaO-MgO-SiO2 system as a promising alternative to 45S5
treatment of cancer: state of art, challenges and future perspectives, Mater. Today
bioactive glass, Bioact. Mater. 5 (1) (2020) 55–65.
Bio (2021) 100.
[44] H. Li, Z. Wu, Y. Zhou, J. Chang, Bioglass for Skin Regeneration, Biomaterials for
[14] S. Kargozar, R.K. Singh, H.-W. Kim, F. Baino, “Hard” ceramics for “soft” tissue
Skin Repair and Regeneration, Woodhead Publishing, Cambridge, 2019,
engineering: paradox or opportunity? Acta Biomater. 115 (2020) 1–28.
pp. 225–250.
[15] F. Baino, J. Barberi, E. Fiume, G. Orlygsson, J. Massera, E.J. Verne, Robocasting
[45] H.E. Skallevold, D. Rokaya, Z. Khurshid, M.S. Zafar, Bioactive glass applications
of bioactive SiO2-P2O5-CaO-MgO-Na2O-K2O glass scaffolds, J. Healthc. Eng.
in dentistry, Int. J. Mol. Sci. 20 (23) (2019) 5960.
(2019), 2019.
[46] J. Chen, L. Zeng, X. Chen, T. Liao, J. Zheng, Preparation and characterization of
[16] A.A. Alshatwi, J. Athinarayanan, V.S. Periasamy, Biocompatibility assessment of
bioactive glass tablets and evaluation of bioactivity and cytotoxicity in-vitro,
rice husk-derived biogenic silica nanoparticles for biomedical applications,
Bioact. Mater. 3 (3) (2018) 315–321.
Mater. Sci. Eng. C 47 (2015) 8–16.
[47] Z. Abbasi, M. Bahrololoom, M. Shariat, R. Bagheri, Bioactive glasses in dentistry:
[17] G. Sharma, M. Kaur, S. Punj, K. Singh, Biomass as a sustainable resource for
a review, J. Dent. Biomater. 2 (1) (2015) 1–9.
value-added modern materials: a review, Biofuel. Bioprod. Bioref. (2020) 1–23.
[48] W.C. Lepry, S.N. Nazhat, Highly bioactive sol-gel-derived borate glasses, Chem.
[18] S.S. Danewalia, G. Sharma, S. Thakur, K. Singh, Agricultural wastes as a resource
Mater. 27 (13) (2015) 4821–4831.
of raw materials for developing low-dielectric glass-ceramics, Sci. Rep. 6 (2016)
[49] V. Miguez-Pacheco, L.L. Hench, A.R. Boccaccini, Bioactive glasses beyond bone
24617.
and teeth: emerging applications in contact with soft tissues, Acta Biomater. 13
[19] G. Sharma, K. Singh, Recycling and utilization of agro-food waste ashes: syntheses
(2015) 1–15.
of the glasses for wide-band gap semiconductor applications, J. Mater. Cycles
[50] S.S. Danewalia, K. Singh, Magnetic and bioactive properties of MnO2/Fe2O3
Waste Manag. 21 (4) (2019) 801–809.
modified Na2O-CaO-P2O5-SiO2 glasses and nanocrystalline glass-ceramics,
[20] M. Roy, A. Bandyopadhyay, S. Bose, Ceramics in Bone Grafts and Coated
Ceram. Int. 42 (10) (2016) 11858–11865.
Implants, Materials for Bone Disorders, Elsevier, 2017, pp. 265–314.
[51] A.J. Salinas, M. Vallet-Regí, Bioactive ceramics: from bone grafts to tissue
[21] C.C. Camilo, C.A. Silveira, R.S. Faeda, J.M. de Almeida Rollo, B. de Moraes
engineering, RSC Adv. 3 (28) (2013) 11116–11131.
Purquerio, C.A. Fortulan, Bone response to porous alumina implants coated with
[52] F. Khan, M. Tanaka, S.R. Ahmad, Fabrication of polymeric biomaterials: a
bioactive materials, observed using different characterization techniques, J. Appl.
strategy for tissue engineering and medical devices, J. Mater. Chem. B. 3 (42)
Biomater. Funct. Mater. 15 (3) (2017) 223–235.
(2015) 8224–8249.
[22] A. Udduttula, J.V. Zhang, P.-G. Ren, Bioinert Ceramics for Biomedical
[53] Z. Sheikh, S. Najeeb, Z. Khurshid, V. Verma, H. Rashid, M. Glogauer,
Applications, Biomedical Sci and Tech Series, Wiley/Scrivener, 2019.
Biodegradable materials for bone repair and tissue engineering applications,
[23] M. Zhao, Y. Sun, J. Zhang, Y. Zhang, Novel translucent and strong submicron
Mater 8 (9) (2015) 5744–5794.
alumina ceramics for dental restorations, J. Dent. Res. 97 (3) (2018) 289–295.
[54] J. Ferguson, M. Diefenbeck, M. McNally, Ceramic biocomposites as biodegradable
[24] S.V. Raj, M. Rajkumar, N.M. Sundaram, A. Kandaswamy, Synthesis and
antibiotic carriers in the treatment of bone infections, J Bone Joint Infect 2 (1)
characterization of hydroxyapatite/alumina ceramic nanocomposites for
(2017) 38–51.
biomedical applications, Bull. Mater. Sci. 41 (4) (2018) 93.
[55] P. Pripatnanont, P. Praserttham, S. Suttapreyasri, N. Leepong, N. Monmaturapoj,
[25] G. Radha, S. Balakumar, B. Venkatesan, E. Vellaichamy, Evaluation of
Bone regeneration potential of biphasic nanocalcium phosphate with high
hemocompatibility and in-vitro immersion on microwave-assisted
hydroxyapatite/tricalcium phosphate ratios in rabbit calvarial defects, Int. J. Oral
hydroxyapatite-alumina nanocomposites, Mater. Sci. Eng. C 50 (2015) 143–150.
Maxillofac. Implants 31 (2) (2016).
[26] J. Liu, Y. Yang, H. Hassanin, N. Jumbu, S. Deng, Q. Zuo, K. Jiang,
[56] A. Camaioni, I. Cacciotti, L. Campagnolo, A. Bianco, Silicon-substituted
Graphene–alumina nanocomposites with improved mechanical properties for
Hydroxyapatite for Biomedical Applications, Woodhead Publishing, Cambridge,
biomedical applications, ACS Appl. Mater. Interfaces 8 (4) (2016) 2607–2616.
2015, pp. 343–373.
[27] H. Xie, L. Zhang, E. Xu, H. Yuan, F. Zhao, J. Gao, SiAlON-Al2O3 ceramics as
[57] M. Yazdimamaghani, M. Razavi, D. Vashaee, K. Moharamzadeh, A.R. Boccaccini,
potential biomaterials, Ceram. Int. 45 (14) (2019) 16809–16813.
L. Tayebi, Porous magnesium-based scaffolds for tissue engineering, Mater. Sci.
[28] Z. Huang, Z. Wang, C. Li, K. Yin, D. Hao, J. Lan, Application of plasma sprayed
Eng. C 71 (2017) 1253–1266.
zirconia coating in dental implant: study in implant, J. oral. Implant. 53 (2018)
[58] V.S. Kattimani, S. Kondaka, K.P. Lingamaneni, Hydroxyapatite - past, present,
264–270.
and future in bone regeneration, BTRI 7 (2016) S36138.
[29] M. Berni, N. Lopomo, G. Marchiori, A. Gambardella, M. Boi, M. Bianchi, A. Visani,
[59] H. Yang, C. Wang, C. Liu, H. Chen, Y. Wu, J. Han, Z. Jia, W. Lin, D. Zhang, W. Li,
P. Pavan, A. Russo, M. Marcacci, Tribological characterization of zirconia
Evolution of the degradation mechanism of pure zinc stent in the one-year study
coatings deposited on Ti6Al4V components for orthopedic applications, Mater.
of rabbit abdominal aorta model, Biomaterials 145 (2017) 92–105.
Sci. Eng. C 62 (2016) 643–655.
[60] S. Mukherjee, S.K. Nandi, B. Kundu, A. Chanda, S. Sen, P.K. Das, Enhanced bone
[30] T. Monetta, A. Acquesta, A. Carangelo, F. Bellucci, TiO2 nanotubes on Ti dental
regeneration with carbon nanotube reinforced hydroxyapatite in animal model,
implant. Part 1: formation and aging in Hank’s solution, Metals 7 (5) (2017) 167.
J. Mech. Behav. Biomed. Mater. 60 (2016) 243–255.
[31] G.I. Benic, D.S. Thoma, I. Sanz-Martin, F. Munoz, C.H. Hämmerle,
[61] Z. Jing, Y. Wu, W. Su, M. Tian, W. Jiang, L. Cao, L. Zhao, Z. Zhao, Carbon
A. Cantalapiedra, J. Fischer, R.E. Jung, Guided bone regeneration at zirconia and
nanotube reinforced collagen/hydroxyapatite scaffolds improve bone tissue
titanium dental implants: a pilot histological investigation, Clin. Oral Implants
formation in-vitro and in vivo, Ann. Biomed. Eng. 45 (9) (2017) 2075–2087.
Res. 28 (12) (2017) 1592–1599.
[62] V. Gupta, D.V. Lyne, M. Barragan, C.J. Berkland, M.S. Detamore, Microsphere-
[32] A.D. Bona, O.E. Pecho, R. Alessandretti, Zirconia as a dental biomaterial, Mater 8
based scaffolds encapsulating tricalcium phosphate and hydroxyapatite for bone
(8) (2015) 4978–4991.
regeneration, J. Mater. Sci. Mater. Med. 27 (7) (2016) 121.

13
S. Punj et al.
[63] G. Rh Owen, M. Dard, H. Larjava, Hydoxyapatite/beta-tricalcium phosphate
biphasic ceramics as regenerative material for the repair of complex bone defects,
J. Biomed. Mater. Res. B Appl. Biomater. 106 (6) (2018) 2493–2512.
[64] C. d’Arros, T. Rouillon, J. Veziers, O. Malard, P. Borget, G. Daculsi, Bioactivity of
Biphasic Calcium Phosphate granules, the control of a needle-like apatite layer
formation for further medical device developments, Front. Bioeng. Biotechnol. 7
(2020) 462.
[65] R. Sarkar, A. Agrawal, R. Ghosh, Preparation of ex-situ mixed sintered biphasic
calcium phosphate ceramics from its Co-precipitated precursors and their
characterization, Trans. Indian Ceram. Soc. 78 (2) (2019) 101–107.
[66] X. Li, Y. Deng, M. Wang, X. Chen, Y. Xiao, X. Zhang, Stabilization of Ca-deficient
hydroxyapatite in biphasic calcium phosphate ceramics by adding alginate to
enhance their biological performances, J. Mater. Chem. B. 6 (1) (2018) 84–97.
[67] I. Atkinson, E. Anghel, L. Predoana, O. Mocioiu, L. Jecu, I. Raut, C. Munteanu,
D. Culita, M. Zaharescu, Influence of ZnO addition on the structural, in-vitro
behavior and antimicrobial activity of sol-gel derived CaO-P2O5-SiO2 bioactive
glasses, Ceram. Int. 42 (2) (2016) 3033–3045.
[68] A. Karthika, L. Kavitha, M. Surendiran, S. Kannan, D. Gopi, Fabrication of
divalent ion substituted hydroxyapatite/gelatin nanocomposite coating on
electron beam treated titanium: mechanical, anticorrosive, antibacterial and
bioactive evaluations, RSC Adv. 5 (59) (2015) 47341–47352.
[69] V. Nicolini, G. Malavasi, L. Menabue, G. Lusvardi, F. Benedetti, S. Valeri,
P. Luches, Cerium-doped bioactive 45S5 glasses: spectroscopic, redox, bioactivity
and biocatalytic properties, J. Mater. Sci. Mater. Electron. 52 (15) (2017)
8845–8857.
[70] V. Nicolini, E. Gambuzzi, G. Malavasi, L. Menabue, M.C. Menziani, G. Lusvardi,
A. Pedone, F. Benedetti, P. Luches, S. D’Addato, Evidence of catalase mimetic
activity in Ce3+/Ce4+ doped bioactive glasses, J. Phys. Chem. B 119 (10) (2015)
4009–4019.
[71] V. Kalyanaraman, T. Kumaravel, S. Murugan, In-vitro cytotoxicity studies of
cerium oxide nanoparticles, Indian J. Nanosci. 4 (1) (2016) 1–5.
[72] K. Jurczyk, M. Kubicka, M. Ratajczak, M. Jurczyk, K. Niespodziana, D. Nowak,
M. Gajecka, M. Jurczyk, Antibacterial activity of nanostructured Ti-45S5 bioglass-
Ag composite against Streptococcus mutans and Staphylococcus aureus,
T Nonferr Metal Soc 6 (1) (2016) 118–125.
[73] B. Karakuzu-İkizler, P. Terzioğlu, B.S. Oduncu-Tekerek, S. Yücel, Effect of
selenium incorporation on the structure and in vitro bioactivity of 45S5 bioglass,
J. Australas. Ceram. Soc. (2019) 1–13.
[74] P. Jha, S.S. Danewalia, G. Sharma, K. Singh, Antimicrobial and bioactive
phosphate-free glass–ceramics for bone tissue engineering applications, Mater.
Sci. Eng. C 86 (2018) 9–17.
[75] C. Stahli, M. James-Bhasin, A. Hoppe, A.R. Boccaccini, S.N. Nazhat, Effect of ion
release from Cu-doped 45S5 Bioglass® on 3D endothelial cell morphogenesis,
Acta Biomater. 19 (2015) 15–22.
[76] M. Eilaghi, M. Montazerian, B.E. Yekta, Effect of partial substitution of K2O for
Na2O on sintering, crystallization and mechanical properties of SiO2-CaO-K2O-
Na2O-CaF2 glass-ceramics, Trans. Indian Ceram. Soc. 75 (1) (2016) 1–6.
[77] A.R. Boccaccini, D.S. Brauer, L. Hupa, Bioactive Glasses: Fundamentals,
Technology and Applications, Royal Soc. Chem., 2016.
[78] N.O. Joy-anne, Y. Su, X. Lu, P.-H. Kuo, J. Du, D. Zhu, Bioactive glass coatings on
metallic implants for biomedical applications, Bioact. Mater. 4 (2019) 261–270.
[79] B. Abd Aladel, I.K. Sabree, S.J. Edrees, Efeects of MgO wt % on the structure,
mechanical ,and biological properties of bioactive properties glass ceramics in the
SiO2, Na2O, CaO, P2O5, MgO system, Int. J. Mech. Eng. Technol. 10 (1) (2019)
97–106.
[80] S. Agarwal, J. Curtin, B. Duffy, S. Jaiswal, Biodegradable magnesium alloys for
orthopaedic applications: a review on corrosion, biocompatibility and surface
modifications, Mater. Sci. Eng. C 68 (2016) 948–963.
[81] P.H. Kuo, S.S. Joshi, X. Lu, Y.H. Ho, Y. Xiang, N.B. Dahotre, J. Du, Laser coating of
bioactive glasses on bioimplant titanium alloys, Int. J. Appl. Glass Sci. 10 (3)
(2019) 307–320.
[82] E. Avcu, F.E. Baştan, H.Z. Abdullah, M.A.U. Rehman, Y.Y. Avcu, A. Boccaccini,
Electrophoretic deposition of chitosan-based composite coatings for biomedical
applications: a review, Prog. Mater. Sci. 103 (2019) 69–108.
[83] F. Baino, S. Hamzehlou, S. Kargozar, Bioactive glasses: where are we and where
are we going? J. Funct. Biomater. 9 (1) (2018) 25.
[84] G.J. Owens, R.K. Singh, F. Foroutan, M. Alqaysi, C.-M. Han, C. Mahapatra, H.-
W. Kim, J.C. Knowles, Sol-gel based materials for biomedical applications, Prog.
Mater. Sci. 77 (2016) 1–79.
[85] M.N. Rahaman, W. Xiao, W. Huang, Bioactive glass implants for potential
application in structural bone repair, Biomed. Glass. 3 (1) (2017) 56–66.
[86] B. Thavornyutikarn, P. Tesavibul, K. Sitthiseripratip, N. Chatarapanich, B. Feltis,
P.F. Wright, T.W. Turney, Porous 45S5 Bioglass®-based scaffolds using
stereolithography: effect of partial pre-sintering on structural and mechanical
properties of scaffolds, Mater. Sci. Eng. C 75 (2017) 1281–1288.
[87] A. Nommeots-Nomm, S. Labbaf, A. Devlin, N. Todd, H. Geng, A.K. Solanki, H.
M. Tang, P. Perdika, A. Pinna, F. Ejeian, Highly degradable porous melt-derived
bioactive glass foam scaffolds for bone regeneration, Acta Biomater. 57 (2017)
449–461.
[88] E.A. Aguilar-Reyes, C.A. León-Patiño, E. Villicana-Molina, V.I. Macías-Andres, L.-
P. Lefebvre, Processing and in vitro bioactivity of high-strength 45S5 glass-
ceramic scaffolds for bone regeneration, Ceram. Int. 43 (9) (2017) 6868–6875.
[89] M. Laczka, K. Cholewa-Kowalska, A. Osyczka, Bioactivity and osteoinductivity of
glasses and glassceramics and their material determinants, Ceram. Int. 42 (13)
(2016) 14313–14325.
14
Ceramics International xxx (xxxx) xxx
[90] M. Vallet-Regi, A. Salinas, J. Roman, M. Gil, Effect of magnesium content on the
in vitro bioactivity of CaO-MgO-SiO2-P2O5 sol-gel glasses, J. Mater. Chem. 9 (2)
(1999) 515–518.
[91] P. Dey, S.K. Pal, I. Banerjee, R. Sarkar, Effect of addition of B2O3 to the sol-gel
synthesized 45S5 bioglass, J. Aust. Cerm. Soc. 56 (2020) 1309–1322.
[92] A.E. Danks, S.R. Hall, Z. Schnepp, The evolution of ‘sol-gel’chemistry as a
technique for materials synthesis, Mater. Horizon. 3 (2) (2016) 91–112.
[93] U. Vijayalakshmi, V. Vaibhav, M. Chellappa, U. Anjaneyulu, Green synthesis of
silica nanoparticles and its corrosion resistance behavior on mild steel, J. Indian
Chem. Soc. 92 (5) (2015) 675–678.
[94] K.C. Kolan, Y.-W. Huang, J.A. Semon, M.C. Leu, 3D-printed biomimetic bioactive
glass scaffolds for bone regeneration in rat calvarial defects, Int. J. Bioprint. 6 (2)
(2020) 274.
[95] B. Zhang, H. Sun, L. Wu, L. Ma, F. Xing, Q. Kong, Y. Fan, C. Zhou, X. Zhang, 3D
printing of calcium phosphate bioceramic with tailored biodegradation rate for
skull bone tissue reconstruction, Bio-Des Manuf. 2 (3) (2019) 161–171.
[96] H. Sun, C. Hu, C. Zhou, L. Wu, J. Sun, X. Zhou, F. Xing, C. Long, Q. Kong, J. Liang,
3D printing of calcium phosphate scaffolds with controlled release of
antibacterial functions for jaw bone repair, Mater. Des. 189 (2020) 108540.
[97] B. Aldemìr, S. Dikici, O. Karaman, H. Oflaz, Development, 3D printing and
characterization of calcium sulfate based scaffolds for bone tissue engineering,
BIYOMUT (2015) 1–4.
[98] F.E. Ciraldo, E. Boccardi, V. Melli, F. Westhauser, A.R. Boccaccini, Tackling
bioactive glass excessive in vitro bioreactivity: preconditioning approaches for
cell culture tests, Acta Biomater. 75 (2018) 3–10.
[99] M. Karadjian, C. Essers, S. Tsitlakidis, B. Reible, A. Moghaddam, A.R. Boccaccini,
F. Westhauser, Biological properties of calcium phosphate bioactive glass
composite bone substitutes: current experimental evidence, Int. J. Mol. Sci. 20 (2)
(2019) 305.
[100] I. Kansal, A. Reddy, F. Muñoz, S.-J. Choi, H.-W. Kim, D.U. Tulyaganov, J. Ferreira,
Structure, biodegradation behavior and cytotoxicity of alkali-containing alkaline-
earth phosphosilicate glasses, J. Mater. Sci. Eng. C. 44 (2014) 159–165.
[101] F. Westhauser, A.S. Senger, D. Obert, F.E. Ciraldo, K. Schuhladen,
G. Schmidmaier, A. Moghaddam, A.R. Boccaccini, Gelatin coating increases in-
vivo bone formation capacity of three-dimensional 45S5 bioactive glass-based
crystalline scaffolds, J. Tissue Eng. Regen. Med. 13 (2) (2019) 179–190.
[102] P. Jha, K. Singh, Effect of MgO on bioactivity, hardness, structural and optical
properties of SiO2-K2O-CaO-MgO glasses, Ceram. Int. 42 (1) (2016) 436–444.
[103] M. Araújo, M. Miola, G. Baldi, J. Perez, E. Verné, Bioactive glasses with low Ca/P
ratio and enhanced bioactivity, Mater 9 (4) (2016) 226.
[104] P. Balasubramanian, T. Buettner, V.M. Pacheco, A.R. Boccaccini, Boron-
containing bioactive glasses in bone and soft tissue engineering, J. Eur. Ceram.
Soc. 38 (3) (2018) 855–869.
[105] K. Xie, L. Zhang, X. Yang, X. Wang, G. Yang, L. Zhang, H. Shao, Y. He, J. Fu,
Z. Gou, Preparation and Characterization of Low Temperature Heat-Treated 45S5
Bioactive Glass-Ceramic Analogues, Biomed. Glass, 2015.
[106] X. Chen, X. Chen, D.S. Brauer, R.M. Wilson, R.V. Law, R.G. Hill, N. Karpukhina,
Sodium is not essential for high bioactivity of glasses, Int. J. Appl. Glass Sci. 8 (4)
(2017) 428–437.
[107] K. Pasiut, J. Partyka, M.M. Bućko, M. Grandys, Ł. Kurpaska, W. Piekarczyk, An
impact of the molar ratio of Na2O/K2O on nanomechanical properties of glaze
materials containing zirconium oxide, J. Alloys Compd. 815 (2020) 152411.
[108] S. Chitra, P. Bargavi, M. Balasubramaniam, R.R. Chandran, S. Balakumar, Impact
of copper on in-vitro biomineralization, drug release efficacy and antimicrobial
properties of bioactive glasses, Mater. Sci. Eng. C 109 (2020) 110598.
[109] T. Himanshu, S. Singh, K. Sampath, M. Prerna, J. Ashish, Studies on preparation
and characterization of 45S5 bioactive Glassdoped with (TiO2+ZrO2) as bioactive
ceramic material, Bioceram. Dev. Appl. 6 (1) (2016) 1–7.
[110] L.P. de Souza, J.H. Lopes, F.V. Ferreira, R.A. Martin, C.A. Bertran, J.A. Camilli,
Evaluation of effectiveness of 45S5 bioglass doped with niobium for repairing
critical-sized bone defect in in vitro and in vivo models, J. Biomed. Mater. Res.
108 (3) (2020) 446–457.
[111] V.O. Soares, J.K. Daguano, C.B. Lombello, O.S. Bianchin, L.M. Gonçalves, E.
D. Zanotto, New sintered wollastonite glass-ceramic for biomedical applications,
Ceram. Int. 44 (16) (2018) 20019–20027.
[112] S. Vyas Kumar, R. Pyare, Destructive and non-destructive behavior of nickel oxide
doped bioactive glass and glass-ceramic, J. Australas. Ceram. Soc. 53 (2017)
939–951.
[113] W.-Y. Choi, H.-E. Kim, Y.-W. Moon, K.-H. Shin, Y.-H. Koh, Production of porous
Calcium Phosphate (CaP) ceramics with aligned pores using ceramic/camphene-
based co-extrusion, Biomater. Res. 19 (1) (2015) 1–7.
[114] S. Pina, R. Rebelo, V.M. Correlo, J.M. Oliveira, R.L. Reis, Bioceramics for
Osteochondral Tissue Engineering and Regeneration, Osteoch Tissue Eng,
Springer, 2018, pp. 53–75.
[115] K. Zhang, Y. Fan, N. Dunne, X. Li, Effect of microporosity on scaffolds for bone
tissue engineering, Regen. Biomater. 5 (2) (2018) 115–124.
[116] M. Bohner, G. Baroud, A. Bernstein, N. Döbelin, L. Galea, B. Hesse, R. Heuberger,
S. Meille, P. Michel, B. Von Rechenberg, Characterization and distribution of
mechanically competent mineralized tissue in micropores of β-tricalcium
phosphate bone substitutes, Mater. Today Proceed. 20 (3) (2017) 106–115.
[117] R. Zhao, S. Chen, W. Zhao, L. Yang, B. Yuan, V.S. Ioan, A.V. Iulian, X. Yang,
X. Zhu, X. Zhang, A bioceramic scaffold composed of strontium-doped three-
dimensional hydroxyapatite whiskers for enhanced bone regeneration in
osteoporotic defects, Theranostics 10 (4) (2020) 1572.
[118] L. Wu, C. Zhou, B. Zhang, H. Lei, W. Wang, X. Pu, L. Liu, J. Liang, Y. Fan,
X. Zhang, Construction of biomimetic natural wood hierarchical porous-structure
S. Punj et al.
bioceramic with micro/nanowhisker coating to modulate cellular behavior and
osteoinductive activity, ACS Appl. Mater. Interfaces 12 (43) (2020)
48395–48407.
[119] A. Motealleh, S. Eqtesadi, A. Civantos, A. Pajares, P. Miranda, Robocast 45S5
bioglass scaffolds: in vitro behavior, J. Mater. Sci. Mater. Electron. 52 (15) (2017)
9179–9191.
[120] J. Barberi, A. Nommeots-Nomm, E. Fiume, E. Verne, J. Massera, F. Baino,
Mechanical characterization of pore-graded bioactive glass scaffolds produced by
robocasting, Biomed. Glass. 5 (1) (2019) 140–147.
[121] X. Liu, M.N. Rahaman, G.E. Hilmas, B.S. Bal, Mechanical properties of bioactive
glass (13-93) scaffolds fabricated by robotic deposition for structural bone repair,
Acta Biomater. 9 (6) (2013) 7025–7034.
[122] C. Bossard, H. Granel, Y. Wittrant, É. Jallot, J. Lao, C. Vial, H.J.B.G. Tiainen,
Polycaprolactone/bioactive glass hybrid scaffolds for bone regeneration, Biomed.
Glasses 4 (1) (2018) 108–122.
[123] H. Elsayed, P. Colombo, E. Bernardo, Direct ink writing of wollastonite-diopside
glass-ceramic scaffolds from a silicone resin and engineered fillers, J. Eur. Ceram.
Soc. 37 (13) (2017) 4187–4195.
[124] M. Saqaei, M. Fathi, H. Edris, V. Mortazavi, N. Hosseini, Effects of adding
forsterite bioceramic on in vitro activity and antibacterial properties of bioactive
glass-forsterite nanocomposite powders, Adv. Powder Technol. 27 (5) (2016)
1922–1932.
[125] H. Shao, X. Yang, Y. He, J. Fu, L. Liu, L. Ma, L. Zhang, G. Yang, C. Gao, Z. Gou,
Bioactive glass-reinforced bioceramic ink writing scaffolds: sintering,
microstructure and mechanical behavior, Biofabrication 7 (3) (2015), 035010.
[126] S.-I. Roohani-Esfahani, P. Newman, H.J.S.r. Zreiqat, Design and fabrication of 3D
printed scaffolds with a mechanical strength comparable to cortical bone to repair
large bone defects, Sci. Rep. 6 (1) (2016) 1–8.
[127] I. Izquierdo-Barba, M. Vallet-Regí, Mesoporous bioactive glasses: relevance of
their porous structure compared to that of classical bioglasses, Biomed. Glass 1
(2015) 140–150.
[128] S. Kumar, M. Malik, R. Purohit, Synthesis methods of mesoporous silica materials,
Mater. Today Proceed. 4 (2) (2017) 350–357.
[129] Y. Ding, S. Tang, B. Yu, Y. Yan, H. Li, J. Wei, J. Su, In-vitro degradability,
bioactivity and primary cell responses to bone cements containing mesoporous
magnesium-calcium silicate and calcium sulfate for bone regeneration, J. Royal
Soc. Int. 12 (111) (2015), 20150779.
[130] Schmitz, A.M. Beltrán, M. Cresswell, A.R. Boccaccini, A structural comparison of
ordered and non-ordered ion doped silicate bioactive glasses, Mater 13 (4) (2020)
992.
[131] I. Atkinson, E. Anghel, S. Petrescu, A. Seciu, L. Stefan, O. Mocioiu, L. Predoana,
M. Voicescu, S. Somacescu, D. Culita, Cerium-containing mesoporous bioactive
glasses: material characterization, in-vitro bioactivity, biocompatibility and
cytotoxicity evaluation, Microporous Mesoporous Mater. 276 (2019) 76–88.
[132] A. Bari, N. Bloise, S. Fiorilli, G. Novajra, M. Vallet-Regí, G. Bruni, A. Torres-Pardo,
J.M. González-Calbet, L. Visai, C. Vitale-Brovarone, Copper-containing
mesoporous bioactive glass nanoparticles as multifunctional agent for bone
regeneration, Acta Biomater. 55 (2017) 493–504.
[133] A.H. Taghvaei, F. Danaeifar, C. Gammer, J. Eckert, S. Khosravimelal,
M. Gholipourmalekabadi, Synthesis and characterization of novel mesoporous
strontium modified bioactive glass nanospheres for bone tissue engineering
applications, Microporous Mesoporous Mater. 294 (2020) 109889.
[134] X. Zhang, D. Zeng, N. Li, J. Wen, X. Jiang, C. Liu, Y. Li, Functionalized
mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration, Sci.
Rep. 6 (2016) 19361.
[135] S. Sanchez-Salcedo, G. Malavasi, A.J. Salinas, G. Lusvardi, L. Rigamonti,
L. Menabue, M. Vallet-Regi, Highly-bioreactive silica-based mesoporous bioactive
glasses enriched with gallium (III), Mater 11 (3) (2018) 367.
[136] W. Wang, Y. Liu, C. Yang, X. Qi, S. Li, C. Liu, X. Li, Mesoporous bioactive glass
combined with graphene oxide scaffolds for bone repair, Int. J. Biosci. 15 (10)
(2019) 2156.
[137] Q. Nawaz, M. Fuentes-Chandía, V. Tharmalingam, M.A.U. Rehman, A. Leal-
Egaña, A.R. Boccaccini, Silibinin releasing mesoporous bioactive glass
nanoparticles with potential for breast cancer therapy, Ceram. Int. 46 (18) (2020)
29111–29119.
[138] J.-H. Lee, A. El-Fiqi, N. Mandakhbayar, H.-H. Lee, H.-W. Kim, Drug/ion co-
delivery multi-functional nanocarrier to regenerate infected tissue defect,
Biomaterials 142 (2017) 62–76.
[139] F. Baino, S. Fiorilli, C. Vitale-Brovarone, Composite biomaterials based on sol-gel
mesoporous silicate glasses: a review, Bioeng 4 (1) (2017) 15.
[140] X. Feng, Y. Wu, F. Bao, X. Chen, J. Gong, Comparison of 3D-printed mesoporous
calcium silicate/polycaprolactone and mesoporous Bioacive glass/
polycaprolactone scaffolds for bone regeneration, Microporous Mesoporous
Mater. 278 (2019) 348–353.
[141] S. Kapoor, A. Goel, A. Tilocca, V. Dhuna, G. Bhatia, K. Dhuna, J.M. Ferreira, Role
of glass structure in defining the chemical dissolution behavior, bioactivity and
antioxidant properties of zinc and strontium co-doped alkali-free phosphosilicate
glasses, Acta Biomater. 10 (7) (2014) 3264–3278.
[142] J.E. Shelby, Introduction to glass science and technology, Royal Soc. Chem.
(2005).
[143] A. Gaddam, H.R. Fernandes, B. Doumert, L. Montagne, J.M. Ferreira, Structure
and thermal relaxation of network units and crystallization of lithium silicate
based glasses doped with oxides of Al and B, Phys. Chem. 19 (38) (2017)
26034–26046.
15
Ceramics International xxx (xxxx) xxx
[144] N. Ranga, E. Poonia, S. Jakhar, A.K. Sharma, A. Kumar, S. Devi, S. Duhan,
Enhanced antimicrobial properties of bioactive glass using strontium and silver
oxide nanocomposites, J. Asian Ceram. Soc. 7 (1) (2019) 75–81.
[145] Z. Tabia, K. El Mabrouk, M. Bricha, K. Nouneh, Mesoporous bioactive glass
nanoparticles doped with magnesium: drug delivery and acellular in vitro
bioactivity, RSC Adv. 9 (22) (2019) 12232–12246.
[146] L. Deilmann, O. Winter, B. Cerrutti, H. Bradtmüller, C. Herzig, A. Limbeck,
O. Lahayne, C. Hellmich, H. Eckert, D. Eder, Effect of boron incorporation on the
bioactivity, structure, and mechanical properties of ordered mesoporous bioactive
glasses, J. Mater. Chem. B 8 (7) (2020) 1456–1465.
[147] S. Herradi, S. Bouhazma, S. Chajri, M. Khaldi, A. El Hachadi, B. El Bali,
M. Lachkar, The effect of strontium and silver on the bioactivity of a quaternary
bioglass in the system SiO2-CaO-Na2O-P2O5, JPhCS 984 (1) (2018), 012011.
[148] G. Kirste, J. Brandt-Slowik, C. Bocker, M. Steinert, R. Geiss, D.S. Brauer, Effect of
chloride ions in Tris buffer solution on bioactive glass apatite mineralization, Int.
J. Appl. Glass Sci. 8 (4) (2017) 438–449.
[149] T. Keenan, L. Placek, M. Hall, A. Wren, Antibacterial and antifungal potential of
Ga-bioactive glass and Ga-bioactive glass/polymeric hydrogel composites,
J. Biomed. Mater. Res. B Appl. Biomater. 105 (5) (2017) 1102–1113.
[150] O. Kuda, N. Pinchuk, O. Bykov, T. Tomila, O. Olifan, M. Golovkova, Development
and characterization of Sr-containing glass-ceramic composites based on biogenic
hydroxyapatite, Nanoscale Res. lett. 13 (1) (2018) 1–8.
[151] X. Lu, J. Kolzow, R.R. Chen, J. Du, Effect of solution condition on hydroxyapatite
formation in evaluating bioactivity of B2O3 containing 45S5 bioactive glasses,
Bioact. Mater. 4 (2019) 207–214.
[152] A. Popa, G. Stan, M. Husanu, I. Mercioniu, L. Santos, H. Fernandes, J.M. Ferreira,
Bioglass implant-coating interactions in synthetic physiological fluids with
varying degrees of biomimicry, Int. J. Nanomed. 12 (2017) 683.
[153] F. Baino, S. Yamaguchi, The use of simulated body fluid (SBF) for assessing
materials bioactivity in the context of tissue engineering: review and challenges,
Biomimetics 5 (4) (2020) 57.
[154] A.L. Macon, T.B. Kim, E.M. Valliant, K. Goetschius, R.K. Brow, D.E. Day,
A. Hoppe, A.R. Boccaccini, I.Y. Kim, C. Ohtsuki, A unified in vitro evaluation for
apatite-forming ability of bioactive glasses and their variants, J. Mater. Sci. Mater.
Med. 26 (2) (2015) 115.
[155] R. Brückner, M. Tylkowski, L. Hupa, D.S. Brauer, Controlling the ion release from
mixed alkali bioactive glasses by varying modifier ionic radii and molar volume,
J. Mater. Chem. B. 4 (18) (2016) 3121–3134.
[156] L. Bingel, D. Groh, N. Karpukhina, D.S. Brauer, Influence of dissolution medium
pH on ion release and apatite formation of Bioglass® 45S5, Mater. Lett. 143
(2015) 279–282.
[157] M. Hafezi, S. Safarian, M.T. Khorasani, N.A.A. Osman, Polyurethane/58S bioglass
nanofibers: synthesis, characterization, and in-vitro evaluation, RSC Adv. 6 (42)
(2016) 35815–35824.
[158] O.S. Aslantürk, In-vitro cytotoxicity and cell viability assays: principles,
advantages, and disadvantages, In Tech (2017) 71923.
[159] X. Gai, C. Liu, G. Wang, Y. Qin, C. Fan, J. Liu, Y. Shi, A novel method for
evaluating the dynamic biocompatibility of degradable biomaterials based on
real-time cell analysis, Regen. Biomater. 7 (3) (2020) 321–329.
[160] E. Mancuso, O.A. Bretcanu, M. Marshall, M.A. Birch, A.W. McCaskie, K.
W. Dalgarno, Novel bioglasses for bone tissue repair and regeneration: effect of
glass design on sintering ability, ion release and biocompatibility, Mater. Des. 129
(2017) 239–248.
[161] F. Hohenbild, M. Arango-Ospina, A. Moghaddam, A.R. Boccaccini, F. Westhauser,
Preconditioning of bioactive glasses before introduction to static cell culture:
what is really necessary? Methods Protoc 3 (2) (2020) 38.
[162] S. Kargozar, N. Lotfibakhshaeish, S. Ebrahimi-Barough, B. Nazari, R.G. Hill,
Stimulation of osteogenic differentiation of induced pluripotent stem cells (iPSCs)
using bioactive glasses: an in-vitro study, Front. Bioeng. Biotechnol. 7 (2019).
[163] A. Moghanian, S. Firoozi, M. Tahriri, A. Sedghi, A comparative study on the in
vitro formation of hydroxyapatite, cytotoxicity and antibacterial activity of 58S
bioactive glass substituted by Li and Sr, Mater. Sci. Eng. C 91 (2018) 349–360.
[164] T.Y. Noorani, N. Luddin, I.A. Rahman, S.M. Masudi, In vitro cytotoxicity
evaluation of novel nano-hydroxyapatite-silica incorporated glass ionomer
cement, J. Clin. Diagn. Res.: J. Clin. Diagn. Res. 11 (4) (2017) ZC105.
[165] C.F. dos Santos, P.S. Gomes, M.M. Almeida, M.-G. Willinger, R.-P. Franke, M.
H. Fernandes, M.E. Costa, Gold-dotted hydroxyapatite nanoparticles as
multifunctional platforms for medical applications, RSC Adv. 5 (85) (2015)
69184–69195.
[166] E. Mancuso, O. Bretcanu, M. Marshall, K.W. Dalgarno, Sensitivity of novel silicate
and borate-based glass structures on in vitro bioactivity and degradation
behaviour, Ceram. Int. 43 (15) (2017) 12651–12657.
[167] A. Li, Y. Lv, H. Ren, Y. Cui, C. Wang, R.A. Martin, D. Qiu, In-vitro evaluation of a
novel pH neutral calcium phosphosilicate bioactive glass that does not require
preconditioning prior to use, Int. J. Appl. Glass Sci. 8 (4) (2017) 403–411.
[168] Y. Lin, W. Xiao, B.S. Bal, M.N. Rahaman, Effect of copper-doped silicate 13-93
bioactive glass scaffolds on the response of MC3T3-E1 cells in-vitro and on bone
regeneration and angiogenesis in rat calvarial defects in-vivo, Mater. Sci. Eng. C
67 (2016) 440–452.
[169] G. Lusvardi, F. Sgarbi Stabellini, R. Salvatori, P2O5-Free cerium containing
glasses: bioactivity and cytocompatibility evaluation, Mater 12 (19) (2019) 3267.
[170] F. Abushahba, E. Söderling, L. Aalto-Setälä, J. Sangder, L. Hupa, T.O. Närhi,
Antibacterial properties of bioactive glass particle abraded titanium against
Streptococcus mutans, Biomed. Phy. Eng. Express 4 (4) (2018), 045002.
S. Punj et al.
[171] S. Begum, W.E. Johnson, T. Worthington, R.A. Martin, The influence of pH and
fluid dynamics on the antibacterial efficacy of 45S5 Bioglass, Biomed. Mater. 11
(1) (2016), 015006.
[172] I. Cacciotti, Bivalent cationic ions doped bioactive glasses: the influence of
magnesium, zinc, strontium and copper on the physical and biological properties,
J. Mater. Sci. Mater. Electron. 52 (15) (2017) 8812–8831.
[173] O. Rodriguez, W. Stone, E.H. Schemitsch, P. Zalzal, S. Waldman, M. Papini, M.
R. Towler, Titanium addition influences antibacterial activity of bioactive glass
coatings on metallic implants, Heliyon 3 (10) (2017), e00420.
[174] S. El-Tablawy, W. Abd-Allah, E. Araby, Efficacy of irradiated bioactive glass 45S5
on attenuation of microbial growth and eradication of biofilm from AISI 316 L
discs: in-vitro study, Siliconindia 10 (3) (2018) 931–942.
[175] L. Zhao, L. Jiang, H. Li, C. Hu, J. Sun, L. Li, F. Meng, Z. Dong, C. Zhou, Synthesis
and characterization of silver-incorporated calcium phosphate antibacterial
nanocomposites for mask filtration material, Compos. B Eng. 153 (2018)
387–392.
[176] A.M. Carvalho, R.A. Cordeiro, H. Faneca, Silica-based gene delivery systems: from
design to therapeutic applications, Pharmaceutics 12 (7) (2020) 649.
[177] Y. Zhou, G. Quan, Q. Wu, X. Zhang, B. Niu, B. Wu, Y. Huang, X. Pan, C. Wu,
Mesoporous silica nanoparticles for drug and gene delivery, Acta Pharm. Sin. B. 8
(2) (2018) 165–177.
[178] E.A. Okoronkwo, P.E. Imoisili, S.A. Olubayode, S.O. Olusunle, Development of
silica nanoparticle from corn cob ash, Adv. Nanoparticles 5 (2) (2016) 135.
[179] N. Permatasari, T.N. Sucahya, A. Nandiyanto, Agricultural wastes as a source of
silica material, Indones. J. Sci. Technol. 1 (1) (2016) 82–106.
[180] C. Kongmanklang, K. Rangsriwatananon, Hydrothermal synthesis of high
crystalline silicalite from rice husk ash, Int. J. Spectrosc. (2015), 2015.
[181] J. Shim, P. Velmurugan, B.-T. Oh, Extraction and physical characterization of
amorphous silica made from corn cob ash at variable pH conditions via sol gel
processing, J. Ind. Eng. Chem. 30 (2015) 249–253.
[182] P. Velmurugan, J. Shim, K.-J. Lee, M. Cho, S.-S. Lim, S.-K. Seo, K.-M. Cho, K.-
S. Bang, B.-T. Oh, Extraction, characterization, and catalytic potential of
amorphous silica from corn cobs by sol-gel method, J. Ind. Eng. Chem. 29 (2015)
298–303.
[183] A. Zielonka, E. Zymanczyk-Duda, M. Brzezińska-Rodak, M. Duda, J. Grzesiak,
M. Klimek-Ochab, Nanosilica synthesis mediated by Aspergillus parasiticus strain,
Fungal Biol 122 (5) (2018) 333–344.
[184] A. Pieła, E. Żymańczyk-Duda, M. Brzezińska-Rodak, M. Duda, J. Grzesiak,
A. Saeid, M. Mironiuk, M. Klimek-Ochab, Biogenic synthesis of silica
nanoparticles from corn cobs husks. Dependence of the productivity on the
method of raw material processing, Bioorg. Chem. (2020) 103773.
[185] N.K. Mohd, N.N.A.N. Wee, A.A. Azmi, Green Synthesis of Silica Nanoparticles
Using Sugarcane Bagasse, AIP conference proceedings, AIP Publishing LLC, 2017,
020123.
[186] J. Athinarayanan, V.S. Periasamy, M. Alhazmi, A.A. Alshatwi, Synthesis and
biocompatibility assessment of sugarcane bagasse-derived biogenic silica
nanoparticles for biomedical applications, J. Biomed. Mater. Res. Part B. 105 (2)
(2017) 340–349.
[187] S. Yucel, Z. Aydın Sinirlioglu, B. Karakuzu, T.M. Temel, Y. Elalmış, A.C. Ozarslan,
Production, characterization and bioactivity of 46S6 bioactive glass from rice hull
ash silica, Adv Mater. Res, Trans Tech Publ (2015) 857–861.
[188] Y. Sevil, P. Terzioglu, Z.A. Sinirlioglu, B.S. Tekerek, Y.B. Elalmis, Synthesis
characterizatio, in vitro degradability and bioactivity of stronuim subsitiuted rice
hull ash silica based melt derived 45S5 bioactive glass, J. Eng. Nat. Sci. 33 (1)
(2015).
[189] D. Kaur, M. Reddy, O. Pandey, In-vitro bioactivity of silicate-phosphate glasses
using agriculture biomass silica, J. Mater. Sci. Mater. Med. 31 (8) (2020) 1–13.
16
Ceramics International xxx (xxxx) xxx
[190] W. Leenakul, T. Tunkasiri, N. Tongsiri, K. Pengpat, J. Ruangsuriya, Effect of
sintering temperature variations on fabrication of 45S5 bioactive glass-ceramics
using rice husk as a source for silica, Mater. Sci. Eng. C 61 (2016) 695–704.
[191] S.-Y. Chen, P.-F. Chou, W.-K. Chan, H.-M. Lin, Preparation and characterization of
mesoporous bioactive glass from agricultural waste rice husk for targeted
anticancer drug delivery, Ceram. Int. 43 (2) (2017) 2239–2245.
[192] R. Shamsudin, F.A. Abdul Azam, A. Hamid, M. Azmi, H. Ismail, Bioactivity and
cell compatibility of β-wollastonite derived from rice husk ash and limestone,
Mater. Sci. 10 (10) (2017) 1188.
[193] S.R. Teixeira, A.E. Souza, C.L. Carvalho, V.C. Reynoso, M. Romero, J.M. Rincón,
Characterization of a wollastonite glass-ceramic material prepared using sugar
cane bagasse ash (SCBA) as one of the raw materials, Mater. Char. 98 (2014)
209–214.
[194] I. Kashif, A. Ratep, Preparation and characterization of oxide glass from sugar
cane waste, Siliconindia 10 (6) (2018) 2677–2683.
[195] E.R. Essien, V.N. Atasie, E.U. Udobang, Microwave energy-assisted formation of
bioactive CaO-MgO-SiO2 ternary glass from bio-wastes, Bull. Mater. Sci. 39 (4)
(2016) 989–995.
[196] A. Hamidi, M. Salimi, A. Yusoff, Synthesis and Characterization of Eggshell-
Derived Hydroxyapatite via Mechanochemical Method: A Comparative Study, AIP
Conference Proceedings, AIP Publishing LLC, 2017, 020045.
[197] K. Ronan, M.B. Kannan, Novel sustainable route for synthesis of hydroxyapatite
biomaterial from biowastes, ACS Sustain. Chem. Eng. 5 (3) (2017) 2237–2245.
[198] S. Palakurthy, K.V. Reddy, S. Patel, P.A. Azeem, A cost effective SiO2-CaO-Na2O
bio-glass derived from bio-waste resources for biomedical applications, Prog.
Biomater. (2020) 1–10.
[199] L. Aguilera-Camacho, C. Hernández-Navarro, K. Moreno, J. García-Miranda,
A. Arizmendi-Morquecho, Research, Improvement effects of CaO nanoparticles on
tribological and microhardness properties of PMMA coating, J. Coating Technol.
12 (2) (2015) 347–355.
[200] R. Choudhary, S. Koppala, S. Swamiappan, Bioactivity studies of calcium
magnesium silicate prepared from eggshell waste by sol-gel combustion synthesis,
J. Asian Ceram. Soc. 3 (2) (2015) 173–177.
[201] L. Xia, Z. Yin, L. Mao, X. Wang, J. Liu, X. Jiang, Z. Zhang, K. Lin, J. Chang,
B. Fang, Akermanite bioceramics promote osteogenesis, angiogenesis and
suppress osteoclastogenesis for osteoporotic bone regeneration, Sci. Rep. 6 (2016)
22005.
[202] A. Kazemi, M. Abdellahi, A. Khajeh-Sharafabadi, A. Khandan, N. Ozada, E. C,
Study of in-vitro bioactivity and mechanical properties of diopside nano-
bioceramic synthesized by a facile method using eggshell as raw material, Mater.
Sci. 71 (2017) 604–610.
[203] J. Li, D. Zhai, F. Lv, Q. Yu, H. Ma, J. Yin, Z. Yi, M. Liu, J. Chang, C. Wu,
Preparation of copper-containing bioactive glass/eggshell membrane
nanocomposites for improving angiogenesis, antibacterial activity and wound
healing, Acta Biomater. 36 (2016) 254–266.
[204] H.T. Vu, C.J. Scarlett, Q.V. Vuong, Phenolic compounds within banana peel and
their potential uses: a review, J. Funct. Foods. 40 (2018) 238–248.
[205] P. Srinath, P.A. Azeem, K.V. Reddy, S.R. Kumar, Synthesis and In-Vitro Bioactivity
of SiO2-CaO-Na2O Glass Using Bio-Waste Resources, AIP Conf Proceed, AIP Pub
LLC, 2019, 030233.
[206] S. Palakurthy, R.K. Samudrala, In vitro bioactivity and degradation behaviour of
β-wollastonite derived from natural waste, Mater. Sci. Eng. C 98 (2019) 109–117.
[207] B. Karakuzu-Ikizler, P. Terzioglu, Y. Basaran-Elalmis, B.S. Tekerek, S. Yucel, Role
of magnesium and aluminum substitution on the structural properties and
bioactivity of bioglasses synthesized from biogenic silica, Bioact. Mater. 5 (2020)
66–73.