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Chapter 1

1.1 Introduction to Nanotechnology


Nanotechnology is an emerging interdisciplinary field that improves
physical, chemical and biological properties of materials. Now days in scientific
research the nanotechnology is a relatively current developing trend.
Nanotechnology is defined as the investigation and use of materials on molecular
and atomic scale in the range below 100 nm [1]. In 1974 the term
“nanotechnology” was firstly invented by the Japanese scientist, Norio Taniguchi
of the Tokyo University of Science. Nanotechnology involves study, creation
and use of materials and systems. The most vital property of nano materials is
the surface-to-volume ratio.
In recent years, scientists are contributing from different areas of expertise
to solve many medical problems. All the biological structures are in Nano scale
nature. Due to this requirement, study of nanomaterials has become the most
innovative field in biomedical science and engineering. The size-dependent
property of nanomaterials is an essential material in biomedical transplant
analyses. Use of nanotechnology is became very important in different applied
fields of science, technology serving as the basis for instruments such as atomic
microscopes and the field ion since twentieth century. Biomaterials implants
have become important part of orthopedic surgery, because of their
osteointegration.
Nanotechnology has confirmed extremely beneficial for use in biomaterial
implants, removing different types of orthopedic defects and traumas. Several
materials like bioactive ceramics, gelatine, biodegradable polymers, and
polysaccharides have been studied as potential material with their unique
properties and benefits. The word “Nano” coins from the Greek word “Nanos”
which means extremely small. The aim of nanotechnology is the production and
application of chemical, physical and biological structures at nanoscales, which
range from separate atoms to submicron dimensions. It is resulted in to the
incorporation of nanostructures into superior system [2-4].The nanotechnology
is assuredly working with strong impact in areas such as medical device,
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electronics and communication, medicines, cosmetics, textile, architectural,


agricultural, metallurgy , defence and many more [5].

Now days an emerging area in nanotechnology is Nano medicine in the


medical field. The product of nanotechnology is Nano medicine and develops
surgical or medical equipment’s and endorse nano materials with new properties
for medical field. The success of nanotechnology is to repair damaged tissues
and remove essential of major surgery. The major success of nanotechnology in
the medical field is;

• Less cost of medical services.


• Less side effects.
• Reduce treatment time.

1.2 Materials used in medical


The material used in medical field for developing non-toxic body implants
is commonly called biomaterials. The well-known definition for biomaterials is
“any pharmacologically inert material, non-viable or viable which is naturally
occurred or synthetic that is able to interacting in a beneficial way with a
surrounding living organism” [6]. Medical implant is a medical structure
manufactured to replace or recover bone or joint or to support a damaged tissue
and bone. Major properties for their implant in body are the mechanical strength
and biocompatibility. Success of orthopaedic surgery depends, on the quality of
the material used to manufacture the implant, its manufacturing methods,
engineering or mechanical properties and biological response [7].
1.2.1 Metal
Metals such as Silver, Gold and stones of gem used as artificial tooth
crowns since 1000 BC. Metals like gold elements for soft tissue sutures for hernia
surgery. The German physician Thomas Gluck, was performed the first hip joint
replacement procedure in 1886. In 1900’s Vanadium and alloys of Vanadium

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used to manufacture bone plates to successful implantation in humans to become


stable bone fractures and accelerate the healing process.
The commonly available materials like Cobalt, Chromium and Titanium
are used as an implant material due to the easy availability and fabrication, good
mechanical properties and corrosion resistance, biocompatibility with
surrounding, suitable density and low cost [8]. Generally metals are also used to
stabilize the broken bones and other tissues while healing proceeds. Jewett rods,
bone plates, intramedullary nails, sutures and screws and many more are
examples of usually used fixation devices [9].Although metals are more
susceptible to electrochemical degradation with high toughness and strength,
they leading to the generation of particulate fragments which may intum elicit
both systemic and local biological response [10].
The biocompatibility of the orthopedic metallic implant is an essential
characteristic because during the implantation the implant metal can corrode the
biological surrounding environment [11]. If the corrosion of the metallic implant
occurs in the human body creates many adverse effects to the nearby tissues.
Some attempts have been made for the fabrication of metallic implant for long-
term orthopaedic surgery applications without any local corrosion [12, 13].
1.2.2 Alloys of some metals
316L stainless steels, titanium alloys and cobalt-chromium alloys are the
metallic materials most regularly used in the body as implant materials. To
improve implant material integration in bone can either be improved by fixation
of cement [14].
The chemical composition of surgical grade type 316L stainless steel
specimen is (wt. %): Fe (65.61), Ni (12.00), Cr (18.00), Mo (2.50), Mn (1.70),
Cu (0.026),Si (0.15) and C (0.02) [15] and chemical composition of Titanium is
(wt %): Ti (99.425), Ferrous (0.20),Oxygen (0.18), Carbon (0.15),Hydrogen
(0.015) and Nitrogen (0.03)[16].In 1926 stainless steel was first developed to
implant purposes. Stainless steel was used due to its simple to its corrosion

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performances, fabrication and good mechanical properties. In the 1950‟s,


316LSS was developed by small level carbon content from 0.07% to 0.02%,
which indicated drastic improvement in corrosion resistance in chloride and
acidic environments [17].

1.2.3 Biomaterial science


The field of biomaterials has become a vital area, as these materials can
improve the quality and the life time of human beings who suffer from various
diseases, accidents and ageing due to determination of normal mobility of the
joints. The science and engineering associated with this field has now led to
multi-million dollar business. Use of biomaterials in medical applications are
commonly used in the clinical laboratory to assay for blood proteins, grow cells
in culture, in biomolecules processing, biotechnological applications, implants,
for fertility regulation in various cattle, oysters aquaculture, gene arrays
diagnostic and also for cell-silicon biochips investigational research. A field of
science which deals with the uses of biomaterials in various biomedical
applications is known as biomaterials science. These materials are commonly
called biomaterials and this material encompasses aspects of medicine, biology,
chemistry and materials science.
1.2.4 Biomaterials and Biocompatibility
Definitions of biomaterial endorsed by several experts in this field are
• A nonviable material basically used in a medical equipment’s and devices,
studied to interact with biological systems are known as biomaterial [18].
• The bioactive material that gives a required similar biological response to
the material interface which results in the formation between the non-
living and living material [19].
• Biomaterial is an inert material by any pharmacological system or a
Combination of substances utilized for incorporation with a living system
to supplement or to change functions of living tissues of organs or
implantation within. In order to achieve that purpose, a biomaterial must

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be in contact with living tissues or body fluids resulting in an interface


between viable and nonviable substances.
• A Biomaterial has ability to replace or augment damaged organs, blood
vessels and tissues, totally or in part and has improved both the quality
and the length of life of several people.
Most of the biomaterials exhibit a stereotyped, non-specific, biological
reaction. Now day’s researchers are focused toward the good engineered surface
which could promote highly precise and spontaneous reactions with cells and cell
containing proteins, modified to a specific application. Biocompatibility is
defined as the ability of a specific material to perform with relative host response
in a specific application. Biocompatibility is not only depends on the intrinsic
physical as well as mechanical characteristics of the material but also its
interaction with tissues [18].
The “appropriate host response” includes, resistance to bacterial colonization,
blood clotting and healing (uncomplicated, normal). Specific applications
include a hemodialysis membrane, a urinary catheter and hip-joint replacement
prosthesis. Important to note that the hemodialysis membrane might be in contact
with patient’s blood for 3 hours, the catheter may be inserted for a week. This
general concept of biocompatibility has been extended recently in the broad class
of tissue engineering, in which in-vitro and in-vivo pathological processes are
harnessed by important selection of cells, materials and metabolic,
biomechanical conditions to regenerate functional tissues.
1.2.5 Selection criteria for biomaterials
The materials used for various biomedical applications should meet the following
requirements [20].
• Good biocompatibility.
• Excellent corrosion resistance in animal body.
• High specific strength.
• Non-toxic

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• Long term stability


• Proper design
• Proper density
• Relatively inexpensive
• Elastic and tribological properties comparable to those of bone
• Appropriate tissue- material interface.
1.2.6 Applications of Biomaterials
Biomaterials are used in:
• Heart valves • Orthopaedics
• Dental implants for tooth fixation • Tissue
• Skin repair devices (artificial tissue)
The following are the details of the biomaterial applications.
1.2.6.1 Heart Valves
From survey it is clear that in USA near about 45-48 % of the valve
replacement procedures would be performed by a mechanical valve implant. The
bileaflet disc heart valve is the most widely valve used. The mechanics includes
two semi-circular discs continuously moving back and forth. This disc not only
allowing flow of blood but also the ability to form a seal to protect backflow.
Pyrolytic carbon is used for coating the valve, this coating material secured to
the surrounding tissue with a mesh of woven fabric named asdu Pont's trade name
for polyethylene terephthalate (Dacron). The body’s tissue are grown up while
incorporating the valve by mesh. [21].
1.2.6.2 Skin Repair
"Artificial" tissues are grown from the patient own cells most of the time.
However, most of the time when the tissue damage of patient is so extreme and
there is not positive situation to use the patient's own cells then artificial tissue
cells are grown. The major difficulty is to find a scaffold that the cells can
specifically grow and organize on the scaffold. The mentioned scaffold must be
biocompatible i.e. cells can adhere to the scaffold, biodegradable and

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mechanically. Glycolic acid and lactic acid copolymer are successful scaffold
[21].
1.2.6.3 Orthopaedics
In orthopaedic applications ceramic, metallic and polymeric biomaterials
are used. Pins, plates and femoral stems etc. are normally used when load bearing
capacity or property of metallic biomaterials is required, similarly when wear
applications in joint replacements is required then ceramics such as alumina and
zirconia are used to assist implant integration hydroxyapatite (HA) is used for
bone bonding applications.
1.2.6.4 Dental Applications
Ceramics including dental porcelains and alumina are uses as tooth
implants. Generally for metallic pins hydroxyapatite has been used for coating
purpose and also use to fill large bone voids resulting from trauma or disease. In
orthodontic devices like plates and dentures polymers are also used for different
purposes.
1.3 Ceramics and Bioceramics
The word ceramic means “burnt stuff” identify from the Greek word
keramos intimating to the fact that the raw materials must be fired by high
temperature heating to form a material with good properties which having useful
range of different engineering properties and applications. Ceramics are basically
homogeneous mixture of two or more metallic or non-metallic elements, which
results in more complex crystal structures. The bond nature in ceramics are of
the atomic bonding which varies from primary, strong bonding between
oppositely charged ions (primarily ionic) to primary, strong bonds formed by
sharing of electrons (primarily covalent) with different ceramics having a
combination of the two types of bond. The bond strength imparts the different
characteristics and properties such as thermal and electrical resistance, high
hardness to the ceramic materials [22, 23]. Bioceramics are the ceramic materials
which are used in biomedical applications. The Bioceramics are used in implant,

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coating to restore natural activity of diseased or damaged/ accidental parts of the


body. In bone substitute or for bone healing process calcium phosphate ceramics
and bioactive glass ceramics this two types of ceramics are used. The other bio
ceramics includes alumina, zirconia and carbon. Ceramics can be categorized or
classified as (i) injectable ones (ii) fast-resorbing and (iii) slow-resorbing [24].
Ceramic composites have good applications in promoting healing property of
bone in clinical practice singly or in combination with other metallic or non-
metallic materials with their osteoconductive, osteoinductive and osteogenic
properties [25-28]. These bio ceramics also plays important role in carriers of
bone cells [29-32], or drugs [33] such as antibiotics [34, 35] and anticancer
medicine or cancer surgery. Advantages of ceramics over metal are their
favourable bioactivity and interaction with the host tissue. The use of ceramic in
dentistry is high because of its inertness in body fluid. Although the ceramic
materials have been used as biomaterials from olden days, due to their inherent
properties such as brittleness and low tensile strength, their application has been
minimum. Recently, introduction of newer ceramics with relative bio inert ness
and high compressive strength has enhanced the use of ceramics as biomaterials.
On the basis of their classifications, bio ceramics are further classified into three
groups namely bio inert ceramics, bioactive ceramics and bioresorbable
ceramics. The bio inert materials are generally used to maintain the mechanical
and physical properties of the implant in physiological environment that is they
are used as a structural support for implants. Owing to the high corrosion
resistance, these materials can stay in the human body environment for a long
period. On the basis of biological responses, dense non-porous materials such as
glass, glass ceramics and calcium phosphate are classified as bioactive ceramics.
The bioactive ceramics are characterised according to their ability to form
chemical bond between the bone and the surrounding tissues. The bioactive
ceramics are widely used as coatings in the orthopaedic and dental implants. The
ceramics that degrade during the implantation are classified as bioresorbable or

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degradable ceramics. Porous aluminium calcium phosphate, HA and calcium


phosphates are potentially used in the fabrication of bioresorbable implants.
Generally, ceramic materials are consists of two or more nonmetallic and
metallic elements to form complex crystal structures than metal elements. The
bond nature in ceramics materials varies from primarily ionic to primarily
covalent with many ceramics having this type of combination of these two bond
types. The bonds strengthen power determines the feature properties of thermal
,electrical resistance and high hardness to the ceramics .This ceramic material
used in biomedical applications divided into three classes according to their
Chemical reactivity with the environment
• completely restorable
• Surface reactive
• Nearly inert
Nearly inert ceramics such as alumina and carbons show small chemical
reactivity even after thousands of hours of exposure to the physiological pH and
this kind of ceramic material show minimal interfacial bonds with living tissues.
One of the first restorable implant material was Plaster of pairs. Its properties
were studied in 1892 and it shows variable resorption rates and poor mechanical
properties. Two types of orthophosphoric acid salt beta tricalcium phosphate
(TCP) and hydroxyapatite (HAP) find well known resorbable biomaterials.
1.3.1 Calcium phosphate based bio ceramics
Calcium phosphate is the well-known biomaterial which has both
beneficial and pathological effects on human body. The beneficial parts fall into
the categories of bioactive and restorable materials [36].There are varieties of
compounds in the calcium phosphate family; many of them are used in the
biomedical applications. The calcium phosphates which exist in various forms
are listed in Table 1.1. Calcium phosphate based biomaterials have been broadly
used in biomedical field in the formation of granulates, super fine powders,
compact porous blocks and different composites [37].

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Phase Formula Structure Ca/P


Dicalcium phosphate CaHPO4 Triclinic 1.00
(DCP)
Dicalcium phosphate CaHPO4.2H2O Monoclinic 1.00
dihydrate
(DCPD)
Tricalcium phosphate Ca3(PO4)2 Hexagonal 1.50
(TCP)
Hydroxyapatite (HA) Ca10(PO4)6(OH)2 Hexagonal 1.67
Tetracalcium Ca4O(PO4)2 Monoclinic 2.00
phosphate (TTCP)
Table 1.1 various phases of calcium phosphate.

The researcher having perceptive in the development of calcium phosphate (Ca-


P) based bioceramic material due to their similar composition with the bone
mineral [38-40] calcium phosphate correspondence in few properties of bone that
comprise bioactivity, biodegradability and osteoconductivity. However different
materials like (e.g., calcium carbonate (CaCO3), calcium sulphate
(CaSO4·2H2O), silica-based bioactive glasses (CaO-Na2O- SiO2) are as well
bioactive, biodegradable and osteoconductive but their mineral bone chemical
composition does not similar. Ceramics applied in orthopedic surgery and
traumatology as bone tissue alternative are mainly of hydroxyapatite
(Ca10(PO4)6(OH)2 ; HAP) which is the most emerging one [41,42]. Synthesized
HA is thermodynamically stable at physiological pH [43] and osteoconductive
has been most frequently used in hard tissues reconstruction and replacement
uses, such as implant coatings [44] and bone substitutes [45] etc. This has opened
the potential for using synthetic HAP in many clinical applications.

BONE COMPOSITION AND STRUCTURE

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Bone is a solid, dense and firm connective tissue that achieve three main
functions such as,
(i) It hold up the body structure,
(ii) It act as a protection shield in opposition to external loadings,
(iii) It supplies a framework that enables skeletal motion.
Bone is having so many degrees of organization which creates difficulty to
analyse it. Especially in the bone composition major components are 69 (wt.) %
calcium phosphate and 21 (wt.) % collagen. In addition to this some other organic
materials alike polysaccharides, proteins, lipids and water are more over present
in some quantities. Collagen is the matrix in the form of fine microfibers. It is
very hard to notice distinct collagen fibers due to its appearance i.e. net–like
mass. The collagen microfiber diameter is differ from 100 to 2000 nm [46].
1.4. Hydroxyapatite
Hydroxyapatite (Ca10(PO4)6(OH)2) also known as hydroxylapatite. It is
non-poisonous bioactive inorganic ceramic compound which having similar
chemical composition of the bone [47]. It provides storage for the control of
calcium uptake and release for the human body. Hydroxyapatite is the hydroxyl
end member of the complex apatite group. The stoichiometric Ca/P molar ratio
is 1.67, and the calculated density is about 3.219 g/cm3. HAP crystallite
possesses a hexagonal structure with the unit cell dimensions of: a = b = 0.9432
nm and c = 0.6881 nm [48, 49]. In the orthepaedics use hydroxyapatite (HA) is
a preferred biomaterial other than any bioceramics such as A–W glass–ceramic
or bio glass or due to its excellent osteoconductivity, bioactivity and
biocompatibility with muscle tissues and some hard tissues. It is applicable as
particulate forms in biomedical applications particularly for bone alternative
material in orthopedics, dentistry and as covering for metallic prosthesis to
enhance their biological properties [47].
Bioactive is a specific type of materials that will make strong chemical
bond with surrounding bone contrary to other different materials like zirconia

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and alumina, which are recognized as alien materials and become enclosed by
fibrous tissue [50].
The hypothesis for application of hydroxyapatite as a biomaterial in the
orthopaedics is the circumstance of using a material i.e. bioactive material having
same composition and crystalline structure as natural calcified tissues. Very
precisely, hydroxyapatite is the only insoluble calcium phosphate compound in
human physiological body fluid while others are soluble and hence, it actively
encourages the bone regeneration at the surface of an implant. It has been
proposed that the use of HAP ceramics biomaterial strength replace the
utilization of bone grafts. The chemistry of this material is logically well
established [51] and significant animal experiments have shown this material to
be both biocompatible and bioactive.
1.4.1 Properties of hydroxyapatite

1.4.1.1 Physical Properties


Hydroxyapatite is a naturally occurring mineral form of calcium apatite.
Generally, pure hydroxyapatite powder is whitish in color. However, naturally
occurring appetites have different colors like yellow, brown or pale green
colorations, alike to the fade of dental fluorosis [49]. Generally, HA can be found
in bones and teeth in human body. So, it is commonly used as a filler to replace
amputated bone or as a coating to promote bone ingrowths into prosthetic
implants. Hydroxyapatite pertain to the hexagonal rhombic prism structure, with
a P63/m space group, and this space group is characterized by three equivalent
a-axes (a1, a2, a3 ), six–fold c–axis perpendicular to at angles 120° to each other.
Unit cell consists of Ca2+, PO 3-and OH- groups closely packed together [52]. HA
has unit cell dimensions of a = 0.9432 nm and c = 0.6101 nm [53].

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Figure 1.1 Schematics of the crystal structure of hydroxyapatite unit cell [54]
and hexagonal format.
1.4.1.2 Chemical Properties
HA is regarded as bioactive material, intimating that the ceramic material
may suffer ionization in vivo. The rate of dissolution of material may be depends
on different factors, such as crystallite size, degree of crystallinity, porosity and
processing pressure, temperature, partial water pressure and some other
conditions. Hydroxyapatite is insoluble in an alkaline solution while highly
soluble in an acidic solution, sparingly soluble in distilled water.
• In distilled water solubility of hydroxyapatite increases with the addition
of electrolytes. Beside it, the solubility of HA changes in the presence of
amino acids, proteins, enzymes, and other organic compounds.
• These solubility characters are nearly related to the biocompatibility of
HA with tissues and its chemical reactivity with other compounds.
However, the rate of solubility depends on differences in porosity,
crystallinity, crystallite size, crystal size and shape. The sintered HA

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solubility is very low and the rate of solubility is 0.1 mg/year in


subcutaneous tissue [55]. Hydroxyapatite reacts actively not only with
lipids and proteins, but also with other organic and inorganic species.
• The most fascinating property of HA is its outstanding biocompatibility
[54] which results the direct chemical bonding with hard tissues [56].
• Physical properties
Colourless or white powder
It has luster in vitreous dull.
It has specific gravity of 3.08
It has uniaxial properties
• Mechanical Properties
Fracture toughness 1.5-7 Mpa√m
Compression strength 300- 600 Mpa
Vickers hardness 3-7 Gpa
Modulus of elasticity 35-120 Gpa
Bending strength 13-38 Mpa
• Constituents of HAP (in wt %)
Calcium (Ca2+) 39.6
Phosphorous 18.5
Ca/P molar ratio 1.667
Ca/P weight ratio 2.151
1.4.2 Clinical properties and application of hydroxyapatite
Hydroxyapatite can be found within the human body in bone and teeth.
Therefore, it is generally used as a filler to replace impacted bone or as a coating
to raise bone growth into prosthetic implants. The applications of hydroxyapatite
in various biomedical fields are listed as follows [57]
• In orthopedic applications to repair bone defects in human body.
• Instantly tooth root replacements
• Replacements for better denture fits for augmentation of alveolar ridge.

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• Application thereof in bone, connective tissue, fat tissue and muscle


• tissue engineering
• Adjuvant to the placement of metal implants
• Maxillo–facial reconstruction
• Middle ear reconstruction
• Fillers in composites, or ceramics
• Nowadays, so many advance implants like, hip replacements and dental
implants, hydroxyapatite used as a coating material. It has been intimating
that this may be promote osteointegration. Porous HA are used for drug
delivery in bone tissues [58].

Figure 1.2 Applications of hydroxyapatite in various biomedical field.

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1.5 Composites
Composites are the materials which have been widely used in dentistry.
Composites were incorporated for various applications by prosthesis designers.
Generally carbon fiber are reinforced with a matrix of ultrahigh-molecular-
weight polyethylene (UHMWPE). These carbon fibres are made by pyrolizing
acrylic fiber to obtain oriented graphitic structure of high modulus of elasticity
and tensile strength. The carbon fibres were 6 – 15 mm in diameter, and they are
irregularly oriented in the matrix. In order for the high modulus property of the
reinforcing fiber to matrix strength, a sufficient interfacial bond between the fiber
and matrix must be achieved during the manufacturing process. This fibre
reinforced composite can then be used to make a variety of implants such as intra-
medullary rods and artificial joint. Since the mechanical properties of these
composites with the proportion of carbon fiber in the composites, it is possible
to modify the material design flexibility to suit the ultimate design of prostheses.
Composites have unique properties and are usually stronger than any of the single
material from which they are made. Workers in this field have taken advantages
of this fact and applied it to some difficult problems where tissue in-growth is
necessary.
Examples:
• Deposited Al2O3 onto carbon
• Carbon / PTFE
• Al2O3 / PTFE
• PLA-coated carbon fiber
The use of composite technology has led to a wide range of new biomaterials,
namely, bio composites materials that offer a great promise to improve the
quality of life of many people. The ceramic materials alone do not possess the
required mechanical properties of the artificial materials to replace natural bone.
Therefore, in order to increase the strength of the artificial material,

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reinforcement (bioactive glass) to matrix (polymer) leads to bio composites


materials. The stiffness of the bio composites materials is very close to that of
bone and hence, finds wide applications in industries.
The major constituent of bones and teeth are composed of HA, a non-
stoichiometric compound with the ability to accept compositional variations in
its sub-lattices. Except calcium, phosphate and carbonate, constituents of mineral
bone consist of different inorganic compounds such as magnesium, fluoride,
chloride, iron, strontium, zinc, sodium and copper. The OH- site of Hap was also
occupied by F- or Cl-. Anionic complexes, such as AsO43-, SO4_, CO32-, SiO44-can
replace PO43- and a big number of metal cations, such asY3+, Zn2+,K+, Cu2+,
Na+,Co2+ , Mn2+, Ni2+,Sr2+, Ba2+, Pb2+, Cd2+ and some trivalent ions of rare
earth elements can be substitute for Ca2+ in little concentrations. Some toxic
metal and semi-metal ions likely as Pb2+ and As5+ can be assimilate easily into
the structure of apatite having clinical ramifications for teeth and bones. Sr-HA
enhanced the proliferation and differentiation of osteoblasts. In addition Sr-HA
might be used as a template to grow new bone and they are proposed for the
treatment of osteoporosis. Europium doped apatite is also used as a biological
probe because of their stable luminescence. Silicon is essential to the growth and
development of biological tissue such as bone, teeth and some invertebrates.
Various metal cations like Mg2+, Zn2+, La3+ , Y3+, In3+ and Bi3+ doped with HA
enhance orthopaedic and dental applications. HA obtained by sol-gel method
with various iron concentrations, could be used for the hyperthermia treatment
of bone tumours. Silver (Ag) was strongly active against bacteria and therefore
Ag doped HA could be considered as an antimicrobial biomaterial which could
be used in implant to avoid infections.Zn2+ ion into HA, is a potential dopant to
enhance the mechanical strength, antimicrobial property and osteointegration.

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1.6 Statement of problem


Literature survey reveals that there are very few reports available on
Biocompatibility and Haemolytic studies of metal–doped Hydroxyapatite
nanoparticles. In vitro investigations such as bioactivity, cytotoxicity,
hemocompatibility etc. attract much attention in connection with the potential
use of bioceramics as a bone replacement material. Bacterial infection after
implantation is a significant rising complication. Even though the use of laminar
flow operating rooms and perioperative antimicrobial prophylaxis the infection
rates near to prosthetic joints range between 1 to 9 % depending on the different
type of implant. An ideal and best biomaterial for bone regeneration is should be
not only bioactive but also resorbable, that is easily replaced by newly formed
bone. Factors which influence bioactivity are composition, crystallinity,
morphology, porosity and specific surface area. The enrichment of Ca and P ions
in the environment raise the bone mineralization that improves the bone
formation. Biocompatibility refers essentially to the compatibility of materials
with the biological systems. This greatly restricts the potential applications of
Hydroxyapatite for use in our living environments. It is necessary to develop safe
and cost effective Biomaterials.
The current area of interest in this field of bioceramic by metal–doped HA
is the modification of HA. The present work aims to prepare biocompatible
responsible metal ion doped HA by solution combustion method. The prepared
nanomaterials were planned to characterize by various sophisticated techniques.
The antibacterial activities of the synthesized nanoparticles were planned to
study by gram positive and gram negative bacterium and cytotoxicity study was
carried out for L929 cell lines and Hela cervical cancer cell lines.
The objectives of the present study involve:
• To develop safe and effective biocompatible materials using undoped
/metal–doped Hydroxyapatite nanoparticles with dopants such as,
Chromium, Silver and Zinc.

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• To characterize structural and morphological properties of undoped


/metal–doped Hydroxyapatite nanoparticles.
• To study antibacterial effect, Cytotoxicity and Hemocompatibillity of
undoped/metal–doped Hydroxyapatite nanoparticles.
• To study in vitro interaction between undoped/metal–doped
Hydroxyapatite nanoparticles with L929 and Hela Cervical cell lines.

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