Biomaterials 287 (2022) 121638

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Biomaterials
journal homepage: www.elsevier.com/locate/biomaterials

Silk sericin-based materials for biomedical applications

Jia Liu a, 1, Lin Shi a, 1, Yan Deng a, b, 1, Meizhen Zou a, b, Bo Cai a, Yu Song a, Zheng Wang a, c, **,
Lin Wang a, b, *
a
Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan,
430022, China
b
Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
c
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

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

Keywords: Silk sericin, a natural protein extracted from silkworm cocoons, has been extensively studied and utilized in the
Silk sericin biomedical field because of its superior biological activities and controllable chemical-physical properties.
Biomaterials Sericin is biocompatible and naturally cell adhesive, enabling cell attachment, proliferation, and differentiation
Tissue engineering
in sericin-based materials. Moreover, its abundant functional groups from variable amino acids composition
Drug delivery
allow sericin to be chemically modified and cross-linked to form versatile constructs serving as alternative
matrixes for biomedical applications. Recently, sericin has been constructed into various types of biomaterials for
tissue engineering and regenerative medicine, including various bulk constructions (films, hydrogels, scaffolds,
conduits, and devices) and micro-nano formulations. In this review, we systemically summarize the properties of
silk sericin, introduce its different forms, and demonstrate their newly-developed as well as potential biomedical
applications.

1. Introduction
Silk is a type of ancient material that has emerging values in
biomedical applications. As a natural protein-polymer secreted in the
glands of lepidopteran insects, the resources of silk are abundant with a
short production cycle [1]. In countries like China and India, the history
of utilizing silk can be dated back thousands of years ago, mostly in
textile industries. Since the initial applications such as silk-based sutures
in medical practice, and excellent biological properties of silk are
gradually revealed, silk has been considered a promising natural mate­
rial for biomedical applications, especially in tissue engineering,
drug/gene delivery, and the emerging smart wearable electronics [1–3].
Silk mainly contains two components: fibroin and sericin. Silk fibroin
has not only been developed as biomedical devices (surgical sutures)
[4], but also becomes an attractive candidate for tissue engineering and
drug delivery system due to its suitable elasticity, mechanical strength,
controllable degradation, and biocompatibility [5–8]. On the contrary,
silk sericin has been ignored and discarded as a waste from the textile
industry for thousands of years, causing environmental pollution and a
waste of natural resources [9]. However, with the advances in sericin
investigation, the discarded sericin is revealed to possess excellent bio­
logical activities as well as fibroin. Other than good-biocompatibility
and low-immunogenicity that are very essential for biomaterials,
recently, it is demonstrated that sericin can support cell attachment and
proliferation [10], and stimulate cell differentiation [11–13]. Further­
more, sericin has excellent humidity preservation and antioxidant ac­
tivities [14,15]. Through modification, precipitation, or cross-linking
with other polymers, sericin could be prepared as stable and controllable
biomaterials, whose morphology, size, and properties (elasticity,
strength, and biodegradability) are able to be tuned precisely. Therefore,
it has attracted attention in the fields of cosmeceuticals, cell culture, and
tissue engineering [16,17]. The recovery and utilization of sericin would
not only minimize environmental problems but also achieve great po­
tential value in biomedical research and medical practice.

* Corresponding author. Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of
Science and Technology, Wuhan, 430022, China.
** Corresponding author. Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of
Science and Technology, Wuhan, 430022, China.
E-mail addresses: zhengwang@hust.edu.cn (Z. Wang), lin_wang@hust.edu.cn (L. Wang).
1
, these authors contributed equally to this work.

https://doi.org/10.1016/j.biomaterials.2022.121638
Received 21 January 2022; Received in revised form 4 June 2022; Accepted 14 June 2022
Available online 17 June 2022
0142-9612/© 2022 Published by Elsevier Ltd.
J. Liu et al.
Fig. 1. The biological activities of sericin, different formats of sericin-based
biomaterials, and their biological applications.
At present, sericin-based biomaterials have been integrated into
tissue engineering constructs to meet various repair and regeneration
demands for different types of tissues, including bulk materials
Fig. 2. Schematic diagram of sericin extraction methods. For wild-type cocoons, there are many different extraction methods for sericin isolation, including physical
extraction methods, biological extraction methods, and chemical extraction methods. The sericin is purified by dialysis and obtained by freeze-drying. For silk
fibroin-deficient cocoons, the intact sericin could be isolated through dissolution in LiBr solution (6 M), dialysis in water, and concentration in PEG solution,
successively.
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Biomaterials 287 (2022) 121638
(hydrogels [18,19], films [20,21], conduits [22–25], scaffolds [26–28]),
and micro-nano structures [29] (Fig. 1). It is worth mentioning that the
unique amino acid composition of sericin contributes to its amphipathic
and acid-base responsiveness, making it a good candidate for drug de­
livery [30]. This review outlines the structure and properties of silk
sericin, summarizes and discusses different types of sericin-based plat­
forms and their applications in tissue engineering and drug delivery, and
offers prospects for future applications.
2. Characteristics and processing methods of sericin
2.1. Sources and types of silkworm cocoons
Silks are generally spun into fibers in the glands of lepidopteran in­
sects, including silkworms, spiders, flies, mites, and scorpions [31]. The
most commonly-used silks originate from silkworms of Bombycidae and
Saturniidae families. According to whether they eat mulberry leaves,
silkworms are divided into mulberry and non-mulberry categories [32].
Silk from Bombycidae family belongs to mulberry silks, such as Bombyx
mori (B. mori), while temperate and tropical tasar silks from Saturniidae
family belong to the non-mulberry silk categories, such as Antheraea
assamensis (A. assamensis), Antheraea pernyi (A. pernyi), and Antheraea
mylitta (A. mylitta) [33,34]. The cocoon layer is mainly composed of silk
fibroin (60%–80%) in the center and sericin (15%–35%) in the periph­
ery, whose proportions are dependent on the species of silkworms [35].
With the extensive exploration of sericin and the help of bioengineering,
new types of silkworm cocoons containing more than 40% or even up to
90% of sericin (from silk fibroin-deficient cocoons) have been developed
[35].
J. Liu et al. Biomaterials 287 (2022) 121638

2.2. Extraction and properties of sericin Table 1

Different sericin extraction methods.
2.2.1. Structure and composition Methods Advantages Limitations Reference
Approximately 90% of the components in sericin are proteins (20 (s)
kDa–400 kDa, 18 amino acids). The remaining components include Thermal-dependent methods
pigments, waxes, sugars, mineral salts, and other impurities [36]. Unlike HTHP (autoclave) No purification Low yield; Heat- [10,49,52,
fibroin, sericin is water-soluble due to its high proportion of polar amino process required; caused degradation; 54,56,57]
acids (>50%), including serine, aspartic acid, and lysine [35,37], which Low cost; Low Destruction of β-sheet
toxicity; Suitable for structures;
allow physical/chemical modifications and crosslinking. The sericin safety evaluation; Abrogating BMP-2/4
protein wrapped around fibroin has a stratified structure, which is High collagen induction
divided into inner, middle, and outer layers according to the water production; High
solubility. From the inner to outer layers (far away from fibroin), the antioxidant activity
and tyrosinase
amount of hydrophobic amino acids in sericin gradually decreases,
inhibition activity
while the content of hydrophilic amino acids gradually increases. Infrared heating High yield and Extra equipment [44]
Therefore, the outer layer has the best water solubility and can be dis­ quality of silk sericin
solved in boiling water within 2 h [37]. In addition, there are two aro­ (SS)
matic amino acids in sericin (tyrosine and phenylalanine) [35], which Chemical reagent-dependent method
Alkaline solution: Application on a Mechanical damage [10,48,
may endow sericin with intrinsic fluorescence [38]. This photo­ Na2CO3, NaOH large scale; Low cost; of silk fibroin (SF); 52]
luminescence property inherits after chemical modification or physical High yield; High Complex purification
crosslinking [39], making sericin a promising biomaterial for biological antioxidant activity process; Large
detection and tracing in vivo. amounts of
wastewater;
The secondary structure of sericin mainly contains random coils and
Extensive
β-sheets, corresponding to the amorphous and crystalline regions, degradation;
respectively [16]. Due to its high content of random coils, sericin ex­ Unbeneficial in
hibits the characteristics of amorphous materials in the dry state, such as fabricating self-
fragility and low mechanical strength. The strength and crystallinity of standing matrices and
self-assembly
sericin-based materials can be controlled by temperature regulation and
particles due to high
chemical modification. Generally, the high temperature tends to destroy water solubility; loss
the β-sheets in sericin [40]. On the contrary, chemical crosslinking (e.g., antityrosinase
glutaraldehyde) leads to stable β-sheet structure formation, thus activity; Massive
reduction of β-sheet
improving the crystallinity and strength of sericin-based materials [41].
Neutral soaps (NS) High quality of High cost; Time- [43,58,
In addition, ethanol-induced dehydration is conducive to the formation fibroin fiber consuming; 59]
of β-sheets from random coils in sericin [42]. Environmental
pollution; Difficulty
2.2.2. Extraction methods in sericin recycling
and reuse
In the textile industry, silkworm cocoons are usually boiled in a so­
Acidic solution: Lower degree of Mechanical damage [10,45,
lution containing sodium carbonate and Marseille soap to remove citric acid, degradation than of SF; Complex 46]
sericin for isolating fibroin. This industrial degumming process is a tartaric acid alkali degumming purification process
traditional and effective approach to separate sericin and fibroin, which Urea buffer Low degree of Inefficient; Extremely [10,52,
degradation; High high cytotoxicity; 60]
however suffers from the high cost of Marseille soap and difficulties in
anti-tyrosinase Massive reduction of
sericin recycling [43]. To cope with these issues, the high-temperature activity for inhibition β-sheet; Abrogating
high-pressure method (HTHP) is employed to dissolve sericin of co­ of melanogenesis BMP-2/4 induction
coons in boiled water under ambient or high pressure, avoiding complex LiBr, LiSCN, NaCl Low degree of Inefficient; Complex [38,61,
refining and purification processes [10]. However, this approach usually degradation; Suitable purification process; 62]
for structural studies Short storage period
results in a low yield, largely because only the outer layer of sericin is
and fabricating pure
dissolved. To enhance sericin dissolution, an infrared (IR) dyeing ma­ sericin based bulk
chine is utilized to heat silkworm cocoons [44]. In this process, water materials
molecules act as abrasives during energy transfer by electromagnetic Surfactant: silk Similar degumming Extra synthesis [58,59]
protein rate to the NS; process of surfactant;
waves, thereby enhancing the sericin shedding. In combination with
surfactant (SPS), Environment Potential biosecurity
heating, some chemical reagents are employed to improve the degum­ alkyl friendly concerns
ming efficiency, including alkaline reagents (sodium carbonate and so­ polyglycoside
dium hydroxide) [34], acid reagents (citric acid and tartaric acid) [45, (APG)
46], and proteases (papain, bromelain, pancreatin, and fungal protease) Biological enzyme-dependent method
Papain, bromelain, Suitable for Low and narrow MW [47,
[47] (Fig. 2). Among them, boiling silkworm cocoons in sodium car­
pancreatin, industrial range of SS peptides; 63–65]
bonate solution (0.02 M) is the most widely used laboratory degumming fungal protease production;
method with high extraction efficiency for both mulberry silkworm completely remove
cocoons (B. mori) and non-mulberry silkworm cocoons (A. mylitta) [48]. SS;
It is important to note that extraction conditions (temperature, time, Homogeneous low Tedious degumming
molecular weight procedure
ratio of cocoons to water, and chemical reagents) not only determine the peptides for cell
yield but also affect the molecular weights and characteristics of isolated culture supplements
sericin. Higher temperature, longer duration, and alkaline reagents may
increase the yield, but they lead to denaturation and degradation of
sericin [49]. 140 Nd-s) allows facile isolation of intact sericin under mild conditions.
To obtain intact protein, sericin is directly isolated from the middle Our group extracted sericin protein from the fibroin-deficient silkworm
silk gland of fifth instar larvae [50,51]. In addition, the emergence of cocoons using lithium bromide (LiBr) solution (6 M) at 35 ◦ C, which
natural fibroin-deficient mutant silkworms (e.g., B. mori, 185 Nd-s, and exhibited a well-preserved protein profile at 60 kDa, 100 kDa, 130 kDa,

3
J. Liu et al.
and >250 kDa. This gentle LiBr extraction method not only preserves the
protein structures but also provides a high yield of sericin (>90%) [38].
The sericin proteins obtained by different extraction methods have
different amino acid profiles, conformation, and molecular weights, as
well as different physical-chemical properties and biological activities
[52]. As a foreign protein, sericin would be recognized by the pattern
recognition receptors of immune cells, which are affected by the protein
conformation of sericin, especially β-sheet structures [53]. Since the
conformation of sericin is highly dependent on the extraction methods,
the receptors activated by sericin and its bioactivities would be varied by
the degumming conditions. For instance, in the sericin obtained by
sonication at 37 ◦ C, the high molecular weight (HMW) fraction of pro­
tein (MW > 30 kDa) possesses more abundance of β-sheet structures
compared with the low molecular weight fraction [54]. Of note, the
sericin protein with the high amount of β-sheet could significantly in­
crease the bone morphogenic protein-2/4 (BMP-2/4) expression in
macrophages and monocytes via activation of Toll-like receptors
(TLR-2/4), which recognize the foreign materials in the body. Thus, such
HMW sericin protein has great osteogenic activity. However, the sericin
isolated by harsh extraction methods (e.g., heat or urea) mainly contains
random coils, which hardly enhance the BMP-2/4 expression. Of note,
the heating treatment could even denature the HMW sericin and
diminish its BMP-2/4 induction ability, likely due to the destruction of
β-sheet structures. Moreover, the degradation of peptide sequences
during the degumming process would also weaken the bioactivities of
sericin. For example, the sericin extracted by heat method exhibited
weaker activities on lactate suppression and interferon-β induction in
vesicular stomatitis virus (VSV) infected RD cells compared with the
intact sericin isolated by LiBr method, likely due to partial degradation
of F5-SP peptide sequence (SEDSSEVDIDLGNLG, an α-glucosidase in­
hibitor) in obtained sericin [55]. Therefore, it is necessary to choose the
appropriate methods for sericin isolation according to the actual appli­
cation requirements and silkworm cocoons (Table 1).
2.2.3. Biological activities
2.2.3.1. Biocompatibility and immunogenicity. Biocompatibility is one of
the most important considerations for materials utilized for biomedical
applications [66,67]. Due to limited understanding and studies, sericin
was once considered the major cause of adverse effects in silk applica­
tions, such as inflammation, allergenicity, and immunogenicity [68]. In
a clinical study, exposure to silk was recognized as an independent
predictor of asthma [69]. The biosafety concerns of sericin have slowed
down and impeded its biomedical applications for decades.
Recently, extensive evidence has demonstrated that sericin itself
does not cause a significant immune response, while the mixture of
sericin and fibroin proteins may induce chronic immune responses with
unclear mechanisms [70–73]. The studies validated that sericin and
sericin-based membranes mildly increased the levels of tumor necrosis
factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) of murine macro­
phages (RAW264.7) in vitro, which were comparable to the polystyrene
plates [51,74,75]. Moreover, in both rabbits and mice, sericin exhibited
immunological inertia [76,77]. To clarify the biosafety of sericin, we
have extracted the degraded and intact sericin from wild-type and
fibroin-deficient mutant silkworm cocoons (B. mori), respectively, and
evaluated their biocompatibility in BALB/c mice [77]. To investigate the
inflammatory responses, the intact sericin-based hydrogel was subcu­
taneously inoculated in BALB/c mice, which did not increase the infil­
tration of macrophages or neutrophils in the tissue of hydrogel
implantation site compared with alginate hydrogel and fibroin hydrogel
at Day 3, 10 and 17. Moreover, these sericin proteins did not signifi­
cantly elevate the levels of IgG (total IgG and sericin-specific IgG) and
IgE compared with fibrinogen (an FDA-approved biomaterial), indi­
cating the low immunogenicity and allergenicity of sericin. These find­
ings indicate that sericin is a biocompatible natural protein suitable for
4
Biomaterials 287 (2022) 121638
biomedical applications.
2.2.3.2. Ability to support cell growth. Sericin is demonstrated to pro­
mote the proliferation and maintain the functions of various types of
cells, including normal mammalian, tumor, and insect cells [78,79].
This characteristic may be attributed to the following aspects: (1) Sericin
can substitute bovine serum albumin (BSA) or fetal bovine serum (FBS)
to support cell culture as a nutrient. For example, serum-free DMEM
medium supplemented with sericin (0.05%) can improve the anti-aging
ability of skin fibroblasts [80], and RPMI1640 medium containing
sericin (0.01%) could maintain the secretory function of pancreatic islet
cells to exert hypoglycemic ability [81]. (2) Sericin is capable of sup­
porting cell adhesion. The sericin-based film was used to culture mouse
fibroblasts (L929), which supported cell attachment and proliferation as
well as styrene culture plate [10]. (3) Sericin can resist cell apoptosis
induced by ultraviolet irradiation via inhibiting caspase-3 activation
[33]. (4) Sericin could also promote cell differentiation. Recently,
sericin was demonstrated to induce rapid differentiation and maturation
of primary human retinal pigment epithelial cells (hRPEs) through
NF-κB pathway. The visual cycle-related genes (RPE65, RDH10, and
CRALBP) were significantly upregulated after sericin treatment in hRPEs
[12,13]. Moreover, sericin modification on the surface of commercially
titanium alloy promoted the adhesion, proliferation, and differentiation
of osteoblasts, and improved the activity of alkaline phosphatase,
thereby promoting bone tissue repair [11].
These forementioned benefits of sericin on cell culture make it
suitable for tissue engineering, and sericin-based biomaterials have been
widely investigated and utilized in bone tissue engineering [82], adipose
tissue engineering [83,84], nerve injury repair [22,25], skin injury
repair [85], as well as corneal epithelial repair [86].
2.2.3.3. Antioxidant activity. The antioxidant properties of sericin are
closely related to its reactive oxygen species (ROS) scavenging activity,
inhibition of lipid peroxidation, anti-tyrosinase, and anti-elastase ac­
tivities [14,15]. Moreover, sericin may enhance the activity of antioxi­
dant enzymes such as superoxide dismutase (SOD), catalase (CAT), and
glutathione peroxidase (GPx) [87,88]. The antioxidant activities are also
related to its high contents of serine and threonine, which provide hy­
droxyl groups to chelate ions (e.g., copper and iron) [15]. In addition,
the pigment molecules (e.g., flavonoids and carotenoids) accumulated in
sericin layers may be one of the causes that endow sericin with antiox­
idant properties and anti-tyrosinase activity [52,89]. Of note, the anti­
oxidant properties of sericin are partly determined by the cocoon strains
and affected by the extraction methods [90–92].
Oxidative stress damage occurs widely in various polar physical
environments and pathological conditions [93]. Due to its antioxidation,
sericin has been used in a variety of fields related to oxidative stress. It is
reported that sericin could effectively absorb ultraviolet (UV), prevent
oxidative damage, and reduce apoptosis of human keratinocytes
(HaCaT) [94,95]. In addition, the sericin (B. mori) enhanced the resis­
tance of human epidermal cells (A431) against chlorpromazine-induced
phototoxicity via increasing intracellular glutathione [95]. These
studies indicate the antioxidant and photoprotective effects of sericin.
Besides UV irradiation, sericin has a protective effect against
oxidative stress damage caused by ultra-low temperatures [96,97].
Cryopreservation is a key technology for breeding and passage, how­
ever, ultra-low temperature freezing induces strong oxidative stress for
cells, tissues, and organs, which reduces their survival rate and biolog­
ical function. Given the benefits of sericin in cell culture and its anti­
oxidant capacity, sericin-based cryoprotectants have been developed
and applied to protect mammalian cells, buffalo semen, and even human
sperm in cryopreservation [98–100]. The sericin addition (0.25%–0.5%)
not only reduced the malondialdehyde in seminal plasma but also
increased the activities of GPx and SOD, therefore improving the
integrity of sperm plasma membrane and survival rate of sperm in
J. Liu et al. Biomaterials 287 (2022) 121638

Table 2
Biomedical applications of sericin-based bulk materials.
Materials Applications Research stage Types of silk Reference
(s)

Films
Sericin Skin tissue engineering In vitro A. mylitta [42]
Sericin Bone tissue engineering In vitro A. pernyi [103]
Sericin/Collagen Wound dressing in vivo, Wistar rats B. mori [104]
Sericin/Bacterial Cellulose Wound healing In vitro B. mori [105]
Sericin/Hydroxyapatite Bone tissue engineering In vitro B. mori [106]
Sericin/Ti-RGD Osseointegration In vitro A. mylitta [11]
Sericin/Agarose-Glycerol Chronic wound treatment In vitro Bivoltine sericin [20]
AgNPs-Sericin/PVA Antibacterial dressing In vitro Sericin powder [107]
AgNPs-Sericin/Agarose Antibacterial dressing In vitro 872. Silkworms [108]
AgNPs-PDA-Sericin/PVA Antibacterial dressing In vitro Unclear [109]
AgNPs-PDA-Sericin/Agarose Wound dressing In vitro 872. Silkworms [110]
ZnONPs-Sericin/PVA Antibacterial dressing In vitro Sericin powder [21]
Ag@ZnONPs-Sericin/Agarose Antibacterial dressing In vitro Unclear [111]
Silver Zinc Sulfadiazine/Sericin Cream Second-degree burn wounds Clinical Trial B. mori [112]
Sericin Cream Pruritus in hemodialysis patients Clinical Trial B. mori [113]
Sericin/Chitosan Cream Pressure Sore Clinical Trial, Recruiting B. mori [133]
Silk Mat Guided bone regeneration (GBR) Clinical Trial B. mori [114]
Hydrogels
Sericin Ischemic Stroke In vitro B. mori, 140Nd-s [18]
Sericin Cartilage regeneration In vitro B. mori, 140Nd-s [19]
Sericin Cell culture and drug delivery In vitro 140 Nd-s [38]
Sericin Ischemic myocardial infarction; In vitro B. mori, 140 Nd- [115]
s
Sericin/Agarose Wound dressing In vitro B. mori [116]
Sericin/Chitosan Skin tissue regeneration in vivo, C57BL/6 mice A. mylitta [117]
Sericin/Alginate Cell and drug delivery In vitro B. mori, 185 Nd- [118]
s
Sericin/Dextran Drug delivery system in vivo, C57BL/6 mice B. mori, Baiyu [39]
Sericin/Polyacrylamide Dermal reconstruction In vitro A. mylitta [119]
Sericin/Poly (γ-glutamic acid) Wound dressing in vivo, Sprague-Dawley Sericin powder [120]
rats
Sericin/Poly (NIPAm/MBA) Wound dressing in vivo, Sprague-Dawley Sericin powder [121]
rats
Sericin/Poly (NIPAm/LMSH) Antibacterial wound dressing in vivo, Sprague-Dawley Sericin powder [122]
rats
Sericin/Graphene oxide Calvarial bone regeneration in vivo, Sprague-Dawley 140 Nd-s [123]
rats
EBN/Sericin hypertrophic scars development at split-thickness skin graft Clinical Trial, Not yet B. mori [133]
donor site recruiting
Scaffolds
Sericin/PVA Full-thickness wound healing in vivo, Sprague-Dawley B. mori [124]
rats
Sericin/Chitosan Wound dressing In vitro B. mori [26]
Sericin/Chitosan Chronic nerve compression treatment in vivo, Sprague-Dawley B. mori, 140 Nd- [27]
rats s
Sericin/Collagen Cartilage regeneration In vitro B. mori [125]
Sericin/Carboxymethyl Cellulose Wound dressing In vitro A. mylitta [126]
Sericin/HAp Osteogenic differentiation In vitro A. pernyi [127]
Sericin/HAp Bone biomineralization In vitro A. pernyi [128]
Sericin/PVA/Glycerin Wound dressing in vivo, Wistar rats B. mori [129]
Sericin/microstructured Bacterial Cellulose Prospective gut repair In vitro B. mori [28]
(mBC)
Sericin/Carbon-Nanotubes (CNTs) Ischemic stroke damage treatment in vivo, C57BL/6 J mice B. mori, 140 Nd- [130]
s
Sericin/PVA Wound dressing for split-thickness skin graft donor site Clinical Trial, Phase 2 B. mori [131]
Sericin/PHMB/Bacterial Cellulose Wound dressing for split-thickness skin graft donor site Clinical Trial, Phase 2 B. mori [132,133]
Sericin/Collagen Wound dressing for split-thickness skin graft donor site Clinical Trial, Recruiting B. mori [133]
Sericin/Chitosan pad Wound dressing for split-thickness skin graft donor site Clinical Trial B. mori [133]
Conduits
Sericin Peripheral nerve regeneration in vivo, Sprague-Dawley B. mori, 140 Nd- [134]
rats s
Sericin/Silicone Peripheral nerve regeneration in vivo, Sprague-Dawley B. mori, 140 Nd- [22]
rats s
Sericin/Fibroin-PLGA Peripheral nerve regeneration in vivo, Sprague-Dawley B. mori [23]
rats
Sericin/Carbon Nanotube Peripheral nerve injury in vivo, Sprague-Dawley B. mori, 140 Nd- [24]
rats s
Devices
XSBR/SSCNT Sensors Human motion and skin temperature detection – Sericin powder [135]
SSCNT ink Human health and activity monitoring – B. mori [136]
Carbon black/Sericin@Fabrics Sweat loss monitoring – Unclear [137]
Flexible Li–S full battery – Unclear [138]
(continued on next page)

5
J. Liu et al. Biomaterials 287 (2022) 121638

Table 2 (continued )
Materials Applications Research stage Types of silk Reference
(s)

Sericin/S/NOCF and Li/NOCF

NOCF: (N/O-codoped carbonized silk
fabric)
SS@CNTs/Acetate Fabrics Textile strain sensor with electromagnetic shielding – Unclear [139]
Ag/Sericin/Au Resistance switching device – Unclear [140]

Table 3 now been widely used for tissue engineering and drug delivery. A variety
Biomedical applications of sericin-based nanoparticles. of sericin-based materials have been fabricated, including bulk materials
Uses of sericin Type of NPs Type of silk Reference (e.g. films, hydrogels, scaffolds, and conduits) and nano-/microparticles.
(s) In this section, we summarized different types of sericin-based materials
Drug delivery and their applications, and reviewed the clinical studies of sericin-based
Coating and AuNP@sericin (in vitro) unclear [177] products (Tables 2 and 3).
stabilizing AgNP@sericin (in vitro) SS powder [173]
agents MSN@sericin (in vivo) B. mori [165]
FGO@sericin (in vitro) B. mori [162] 3.1. Bulk formats
Sericin-drug FA-SND (in vivo) B. mori [172]
coupling FA-Ser-Chol (in vitro) SS power [178]
Pure sericin RSV@Ser (in vitro) unclear [167] 3.1.1. Films
nanocarrier ATR@Ser (in vivo) B. mori [166] Films (or membranes) are highly flexible and elastic formations that
Sericin-polymer Sericin/PBLG (in vivo) B. mori [169,170] allow gas exchange, water vapor transmission, and bacteria segregation
nanocarrier Sericin/poly- B. mori [168]
[141]. Skin, an important organ consisting of epidermis and dermis
ethylcyanoacrylate (in
vivo) layers, is easily damaged by acute trauma or chronic ulcers [142]. Thus,
Sericin/PLA (in vitro) B. mori [171] a variety of films have emerged to promote wound healing as dressing
SC-GG-RBA (in vitro) B. mori [179] materials [143].
MA-GG–SS–CS (in vitro) B. mori [180] As sericin possesses great biocompatibility and inherent bioactivities
Reducing agent
Nano Ag (in vitro) SS powder [181]
(supporting cell adhesion and proliferation, antioxidant property), it is
Nano Ag (in vitro) B. mori/ [175] suitable to be generated as films for skin regeneration [71]. For instance,
Samiacynthiaricini the glutaraldehyde-crosslinked sericin films and sericin/collagen com­
Nano manganese dioxide SS powder [176] posite films have been prepared for wound healing, which could support
(in vivo)
the attachment and proliferation of various types of cells (e.g., fibro­
Others
Anti-bacterial Sericin/TiO2 (in vitro) Raw silk filaments [182] blasts and keratinocytes) [42,104]. Sericin was also loaded in bacterial
anti- Sericin/alginate (in vivo) B. mori [183] cellulose (BC) films to fabricate sericin-functionalized BC composites
inflammatory (Fig. 3A) [105]. The sericin released from composites accelerated the
Would healing Sericin/magnesium Unclear [184] healing process, improved extracellular matrix production, and reduced
hydroxide (in vitro)
scar tissue formation. Furthermore, to endow the dressing materials
with antibacterial functions, the nanoparticles with antibacterial activ­
cryopreservation [98,100]. Thus, sericin would be an alternative with ity (silver or zinc oxide nanoparticles) were embedded in sericin-based
low cost to serum in cryopreservation for protecting cells and embryos films [108,111,144–146].
from oxidative stress damage. Sericin films can also promote bone regeneration. As shown in
Fig. 3B, sericin was wrapped on the metallic implant to enhance the
2.2.3.4. Metabolic regulation activity. As a dietary additive, sericin is adhesion, proliferation, and differentiation of osteoblast-like cells,
demonstrated to regulate glycolipid metabolism. In a type 2 diabetes rat which could benefit bone regeneration [11]. In another work, the
model induced by high-glucose/fat diet combined with streptozotocin, calcium-deficient carbonate apatite was in situ mineralized on sericin
oral administration of sericin significantly increased the levels of liver film to generate a hydroxyapatite/sericin composite film, which was
glycogen and insulin signaling pathway-related factors (IR, IRS-1, PI3K, capable of promoting the adhesion and viability of human osteosarcoma
and AKT) and reduced the blood glucose, suggesting that sericin may MG-63 cells [106].
regulate glucose metabolism through insulin-PI3K/AKT signaling
pathway [88,101]. Moreover, sericin could also regulate the lipid 3.1.2. Hydrogels
metabolism of obese animals [102]. Interestingly, sericin could facilitate Hydrogel is a three-dimensional (3D) network containing physically/
antiviral response by regulating glucose metabolism [55]. The sericin chemically crosslinked materials and a large amount of aqueous solu­
(B. Mori) and its derived F5-SP peptide (SEDSSEVDIDLGNLG) were tion, which is widely used in drug delivery and tissue engineering [147].
identified to be α-glucosidase inhibitors, which could suppress cellular Sericin protein contains a lot of polar amino acids that offer plentiful
glycolysis. By reducing lactate production, sericin significantly side groups for chemical crosslinking [148]. However, the sericin ob­
enhanced the innate immune response by promoting interferon tained by harsh degumming methods is inevitably degraded, which is
expression through RIG-I-MAVS signaling pathway, thus resulting in difficult to form stable hydrogels itself. To generate stable sericin net­
excellent anti-RNA virus activity in vitro and in vivo. These studies works, the degraded sericin was usually combined with other polymers
indicate the potential value of sericin for the treatment of metabolic (e.g., collagen, gelatin, chitosan, and poly (vinyl alcohol)) to form
diseases and viral infections. composite hydrogels [16,29,119,120,149]. For instance, a sericin/poly
(NIPAm/LMSH) nanocomposite hydrogel with antibacterial properties
3. Sericin-based biomaterials with different formats and was developed as a wound dressing [122]. The embedding of sericin
corresponding applications increased the internal pore sizes of interpenetrating network (IPN)
hydrogels, and interestingly shifted the structure of networks from
Due to its good biocompatibility and bioactivities, silk sericin has honeycomb to layered. Importantly, the sericin composite hydrogels
could adsorb bacteria, and interrupt the physiological activities of the

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J. Liu et al.
Fig. 3. Preparation and applications of sericin-based films. (A) Sericin-Bacterial cellulose (BC) composite films were fabricated by a solution impregnation method,
which could accelerate the wound healing process, improve extracellular matrix production, and reduce scar formation [105]. (B) Sericin film was wrapped on the
metallic implant to enhance the adhesion, proliferation, and differentiation of osteoblast-like cells, thus promoting bone regeneration [11].
attached bacteria by released micromolecular sericin, thereby achieving
an antibacterial effect. Similarly, a lysozyme-loaded sericin/agarose
hydrogel showed excellent antimicrobial activities and water absorption
properties (Fig. 4A), possessing great potential in skin regeneration
applications [150]. In addition, some other composite hydrogels (e.g.,
sericin/poly (γ-glutamic acid), sericin/polyacrylamide, and ser­
icin/chitosan hydrogels) were prepared as wound dressings, since
sericin could encourage fibroblasts proliferation and migration [85,117,
119,120]. Aside from preparing simple hybrid hydrogels, our group
introduced hydrazide groups to sericin molecules. The sericin-derivative
was subsequently crosslinked with oxidized dextran to fabricate an
injectable sericin/dextran composite hydrogel for sustained release of
doxorubicin (DOX) in tumor local [39]. This hydrogel induced little
immune response and inherited the photoluminescent property of
sericin for in vivo tracing. In addition to polymers, inorganic nano­
particles (AgNPs or Ag@MOF-GO) also have been incorporated into
sericin hydrogels to endow them with antibacterial properties or he­
mostatic activity [151,152].
Since the harsh extraction procedures induce severe degradation and
denaturation of sericin, stable pure sericin networks were rarely pre­
pared and investigated. To overcome the limitation, our group isolated
the intact sericin using a mild extraction method (LiBr method) from
fibroin-deficient mutant silkworm strains (185 Nd-s and 140 Nd-s) [38].
Such sericin could be readily crosslinked with chemical agents (e.g.,
glutaraldehyde, genipin) or self-assemble under physical sonication to
form pure sericin hydrogels [38,153]. As shown in Fig. 4B, the
glutaraldehyde-crosslinked sericin hydrogel with photoluminescence
was able to support cell adhesion, proliferation, and long-term survival
[38]. Moreover, the sericin hydrogel could sustained-release bioactive
reagents, making it a promising candidate for tissue engineering and
regenerative medicine. Besides, the intact sericin was crosslinked with
genipin to generate a pure sericin hydrogel for repairing ischemic stroke
and ischemic myocardial infarction [18,115]. This hydrogel could sup­
port the attachment and growth of neurons in vitro and exhibited
intrinsically neurotrophic and neuroprotective effects [18]. In addition,
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Biomaterials 287 (2022) 121638
this hydrogel could reduce the infarct size, inhibit the inflammatory
response and apoptosis, and promote the formation of new blood vessels
by injection into the acute myocardial infarction area in mice, thus
leading to the recovery of cardiac function [115].
Notably, using the degraded sericin, we have also generated an
injectable, photo-crosslinked pure sericin hydrogel [19]. The meth­
acryloyl groups were introduced to sericin to synthesize sericin meth­
acryloyl (SerMA), which could be crosslinked in situ under UV
irradiation through photo-polymerization. This SerMA hydrogel could
support cell attachment and proliferation as well as the intact sericin
hydrogels. Subsequently, graphene oxide was mingled into the
photo-crosslinked SerMA hydrogels (SMH/GO) to enhance the me­
chanical strength, whose compressive stress was increased by ~2 folds
(Fig. 4C) [123]. Notably, the sericin promoted bone marrow stromal
cells (BMSCs) migration, and the embedded graphene oxide specifically
encouraged osteogenesis differentiation of BMSCs. Thus, as an artificial
bone substitute, the hydrogel significantly accelerated calvarial bone
regeneration in mice compared with the commercial artificial bone
(Osteobone). Moreover, the degraded sericin-derivative (SerMA) was
used to generate AgNPs embedded cryogels (SMC@Ag), which exhibited
improved hemostatic and antibacterial activities compared with com­
mercial gelatin sponge [154].
3.1.3. Scaffolds
During tissue regeneration, biomaterial scaffolds are desired to
provide an instructive environment to recruit cells and promote cell
proliferation, therefore accelerating healing cascades [155]. Sericin has
been prepared as scaffolds through foam processing, solvent casting, or
freeze-drying methods for tissue engineering.
For promoting skin tissue regeneration, a sericin/polyvinyl alcohol
(PVA) scaffold was generated by freeze-drying and subsequently
precipitated in ethanol [124]. The scaffolds could promote L929 fibro­
blasts proliferation in vitro, and significantly accelerate the full-thickness
wound healing in rats. Moreover, a sericin/PVA scaffold containing
glycerin was fabricated [129]. The addition of glycerin effectively
J. Liu et al. Biomaterials 287 (2022) 121638

Fig. 4. Preparation and applications of sericin-based hydrogels. (A) A lysozyme-loaded sericin/agarose hydrogel was generated by the solution impregnation
method, which showed excellent antimicrobial activities and great water absorption properties, making it a potential alternative for wound dressing [150]. (B) Intact
sericin isolation from fibroin-deficient mutant silkworm strains, which could be readily crosslinked to fabricate sericin hydrogel [38]. (C) A sericin/graphene oxide
composite hydrogel was generated for calvarial bone regeneration, which could promote BMSCs migration and osteogenesis differentiation [123].

improved the flexibility properties and reduced the wound adhesion
properties due to its uniform pore structure, which might be contributed
to the effect of glycerin in reducing the phase separation between sericin
and PVA. Importantly, the sustained release of sericin made the scaffolds
appropriate for long-term healing of the wound.
For bone and cartilage regeneration, the sericin scaffolds mineralized
with hydroxyapatite (HAps) were prepared by a wet precipitation
method [127,128]. These scaffolds could not only support BMSCs
adhesion and proliferation but also promote the osteogenic
differentiation of BMSCs.
For nerve regeneration, our group fabricated a nerve growth factor
(NGF)-loaded chitosan/sericin composite scaffold for the treatment of
chronic nerve compression (Fig. 5A) [27]. This scaffold could promote
Schwann cells adhesion and proliferation. In a preclinical chronic nerve
compression rat model, the NGF-loaded scaffold promoted nerve func­
tional recovery via alleviating neuralgia, enhancing nerve conduction
velocity, accelerating microstructure recuperation, and improving
gastrocnemius muscles dystrophy. Moreover, an injectable

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J. Liu et al. Biomaterials 287 (2022) 121638

Fig. 5. Preparation and applications of sericin-based scaffolds and conduits. (A) A chitosan/sericin composite scaffold loaded with nerve growth factor (NGF) was
fabricated and applied for treating chronic nerve compression [27]. It can promote nerve functional recovery in a preclinical chronic nerve compression rat model via
alleviating neuralgia, enhancing nerve conduction velocity, accelerating microstructure recuperation, and improving gastrocnemius muscles. (B) A sericin nerve
conduit loaded with clobetasol was designed and fabricated for repairing a 10 mm gap in peripheral nerve in the rat injury model [24]. (C) A carbon nanotube/sericin
nerve conduit was employed to recover the peripheral nerve injury, showing great regenerative performance combined with electrical stimulation [25].

carbon-nanotubes-doped sericin scaffold (CNTs-SS) with programmable
shape-memory property was generated for treating ischemic stroke
[130]. The shape of CNTs-SS could be pre-designed according to the
personalized stroke damage, thus allowing injection into the cavity of
mice to cover the damage. It was worth noting that CNTs-SS scaffold
could deliver bone marrow mesenchymal stem cells (BMSCs) to the
brain tissue and then functionally promote BMSCs’ neuronal differen­
tiation, thus promoting stroke repair.
3.1.4. Conduits
Nerve guidance conduit (NGC) is generally formed with a hollow
tube shape composed of natural or synthetic materials, which serves as
an alternative to grafted nerve tissue for repairing peripheral nerve
injury [134]. Due to the good biocompatibility and biodegradability,
sericin has been employed to generate conduits for nerve regeneration.
In our previous work, a nerve guidance conduit was generated by sericin
and silicone for peripheral nerve regeneration [22]. This sericin/silicone
conduit effectively promoted recovery of nerve morphology and func­
tions during repairing a 5-mm gap defect in a sciatic nerve transection
model. To improve the repair performance, clobetasol (a glucocorticoid
receptor agonist) was loaded in a sericin nerve conduit for treating a
longer gap defect (10 mm) [24] (Fig. 5B). The clobetasol-loaded sericin
conduit successfully repaired the nerve defect in rats, during which the
degradation products of conduit promoted neurotrophic factors secre­
tion and clobetasol upregulated the myelin-related genes in Schwann
cells. Moreover, carbon nanotube (CNT) was introduced into the sericin
conduit to endow it with electrical conductivity, which improved the
performance of CNT/sericin conduit for restoring nerve structure and
functions in a nerve injury rat model (10-mm gap defect) (Fig. 5C) [25].
3.1.5. Devices
As a degradable and biocompatible protein, sericin recently has
attracted attention in the fields of electronics and sensing apart from
tissue engineering and drug delivery. The hydrophilic sericin usually
serves as a binder and stabilizer to improve the electrical properties of
flexible wearable sensors. Flexible devices based on nanocarbon mate­
rials are one of the important methods to produce wearable electronics.
The sericin-modified carbon nanotubes (CNTs) were combined with
carboxylic styrene-butadiene rubber (XSBR) to generate a flexible
network, which could serve as multi-functional sensors for detecting
weak deformation and temperature variation (Fig. 6) [135]. Such
wearable devices provide a convenient strategy for monitoring human
healthcare and motion. Similarly, in combination with sericin and CNTs,
a bio-ink (SSCNT) was generated to draw multifunctional circuits on
various substrate surfaces, and subsequently fabricate electrocardio­
gram electrodes, respiration sensors, or electrochemical sensors for
human healthcare monitoring [136].
Lithium-sulfur batteries are promising high-energy power sources for
flexible wearable electronics, but are limited by the instability and low
utilization of lithium-sulfur as well as poor electrode flexibility. The
sericin was utilized as adhesive binders to stabilize sulfur cathode, and
then combined with the carbonized fibroin fabric to fabricate lith­
iophilic and thiophilic stable electrodes with high areal capacity and
great bending capability [138]. Moreover, sericin was selected to
generate a resistance-switching device with multilevel nonvolatile
memory, as it possessed large resistance OFF/ON ratio and remained

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J. Liu et al.
Fig. 6. Fabrication process and applications of the XSBR/SSCNT sensors [135]. Schematic illustration of the preparation (A) of flexible XSBR/SSCNT sensors and the
applications for human motion (B) and temperature detection (C).
insulation in native state [140]. The Ag/sericin/Au sandwich structure
was performed as a simple metal-insulator-metal (MIM) cell structure
and displayed significantly multilevel resistance-switching memory
performance.
3.1.6. Clinical studies
Currently, most studies of sericin-based materials remain at the
laboratory stage, and only several clinical studies have been performed.
In a randomized double-blind clinical trial, silver zinc sulfadiazine
cream supplemented with sericin was used for treating second-degree
burn wounds. The sericin-loaded cream (22.42 ± 6.33 days) signifi­
cantly shortened wound healing time compared with the cream without
sericin (29.28 ± 9.27 days), and no infection or severe adverse reactions
occurred in patients [112]. This is the first case of sericin safely and
effectively used in clinical research. In another clinical trial, topical
administration of sericin cream significantly reduced pruritus in he­
modialysis patients and improved quality of life in uremia patients
compared to placebo [113].
To demonstrate the potential of sericin in other applications, Por­
nanong Aramwit et al. developed a sericin/PVA hybrid scaffold, which
promoted wound healing more efficiently than the PVA scaffold without
sericin in rats. This result was further confirmed in a clinical trial of
treating split-thickness skin graft (STSG) donor site. The sericin/PVA
scaffold markedly shortened the time for complete healing of the pa­
tient’s wound skin compared to the commercially available Bactigras®
dressing [131].
In another study by this team, a bacterial cellulose wound dressing
(BCSP) containing sericin and polyhexamethylene biguanide was
developed. When implanted subcutaneously in rats, the BCSP elicited a
lower inflammatory response compared to Bactigras®. Clinical patch
experiments were performed on the normal skin of healthy volunteers,
and no skin irritation symptoms appeared, such as erythema, melanin
accumulation, edema, and papules [132]. Further clinical trials were
conducted for the treatment of STSG donor sites with this dressing
(BCSP). Although BCSP did not significantly accelerate the wound
healing process compared with Bactigras®, the BCSP treatment
encouragingly improved the wound quality and reduced the patient’s
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Biomaterials 287 (2022) 121638
wound pain. In addition, no adverse events such as infection occurred
[133]. The team also intends to conduct some other clinical trials,
including the clinical efficacy of sericin/collagen hybrid scaffold on
STSG donor sites, the clinical efficacy of sericin hydrogel sheet
impregnated with bird’s nest extract for the prevention of scar formation
in patients with STSG donor sites, and the clinical efficacy of ser­
icin/chitosan pad on STSG donor sites. However, the results of these
clinical trials are currently unclear. Seong-Gon Kim et al. conducted a
clinical trial of silk mats for guided bone regeneration (GBR), which
contains both fibroin and sericin. Compared with the commercial dPTFE
membrane, the effect of the silk mat on GBR after third molar extraction
surgery was comparable, and no obvious complications occurred [114].
Currently, clinical trials of sericin-based materials are still sparse, the
types of products are relatively simple, and the application scenarios are
circumscribed. This may be one of the reasons that hinder the
commercialization of sericin products. Therefore, more efforts and at­
tempts are needed in this regard.
3.2. Particles
3.2.1. Nanoparticles
With the advancement of nanotechnology, nanomaterials have been
widely used for controlled drug delivery and diagnosis. Generally,
nanostructure endows materials with unique physical and chemical
properties, such as high surface area, dispersion, and enhanced perme­
ability and retention (EPR) effects, which make nanomaterials exten­
sively applied in drug delivery [156,157]. Due to its modifiable structure
and excellent biological characteristics (e.g., amphiphilicity, pH
responsiveness, biodegradability, and good biocompatibility), sericin
possesses unique advantages in fabricating nano- and micro-scale ma­
terials [16]. In Table 3, we have summarized the recent studies of
sericin-based micro/nano-structures.
The stability and dispersibility of nanoparticles (NPs) in the physi­
ological environment are important factors, because aggregation of
either the NPs themselves or the blood cells caused by NPs may cause
inflammation and acute toxicity [158]. Thus, the NPs should be modi­
fied or coated with dispersion stabilizers to enhance stability and reduce
J. Liu et al. Biomaterials 287 (2022) 121638

Fig. 7. Preparation and applications of sericin-based nanostructures. (A) Sericin was wrapped on mesoporous silica nanoparticles (MSNs) to improve their dispersion
and stability in aqueous solutions. At the same time, serving as a gatekeeper, sericin responded to protease and acidic condition to control the release of loaded drugs
[165]. (B) Sericin-PBLG micelles enhanced the delivery of DOX for the treatment of drug-resistant tumors [169]. (C) Sericin-based nanoparticles underwent a charge
reversal process due to the change of amino/carboxyl ratio under different pH conditions, thereby achieving pH-dependent cellular internalization and drug release
in the tumor [30]. (D) Sericin was used as a reducing agent to assist the synthesis of silver nanoparticles [173].

serum protein adsorption in the circulatory system [159–161]. Sericin
contains abundant polar amino acids, which can interact with water
molecules to form a hydration layer. In this respect, sericin is possible to
be used as a dispersion stabilizer to enhance the stability of
nanoparticles.
Fluorinated graphene (FGO) is a high-efficiency drug carrier and
photoacoustic contrast agent. Its highly inert and repellent surface
makes it extremely unstable in aqueous solutions. To solve this problem,
sericin was developed as a stabilizer to fabricate water-steady FGO
nanocarriers, which efficiently loaded curcumin and achieved a pro­
longed circulation in blood [162]. Similarly, by coating with sericin, the
nanomaterials (e.g., carbon nanotubes, zeolitic imidazolate
framework-8) can obtain enhanced stability and biocompatibility [139,
163,164]. In our previous study, sericin was wrapped on DOX-loaded
mesoporous silica nanoparticles (MSNs) as a gatekeeper through
pH-sensitive hydrazone linkages, forming a pH/protease dual respon­
sive drug delivery system [165]. The sericin coating endowed silica
nanoparticles with good dispersibility and prevented drug premature
leakage. When the nanoparticles were internalized into tumor cells
through endocytosis, the acidity microenvironment of lysosomes
cleaved the pH-sensitive hydrazone bonds and the protease in lysosomes
degraded sericin peptides, thus leading to DOX release (Fig. 7A).
Except for coating nanoparticles, sericin itself can be prepared as
nanocarriers for insoluble molecules (e.g., resveratrol and resveratrol) to
enhance their therapeutic effects and reduce systemic toxicity [166,
167]. Moreover, nanocomposites formed by sericin and other polymers
(e.g., synthetic polymers, polysaccharides, and proteins) have been
generated as therapeutic drug carriers [168–171].
Sericin/poly-ethylcyanoacrylate nanospheres were prepared through
interfacial polymerization to improve the bioavailability of fenofibrate
(a lipid-lowering drug) [168]. In another study, an amphiphilic polymer
micelle (sericin backbone and poly (γ-benzyl-L-glutamate) side chains)
was fabricated through ring-opening polymerization [169]. Because of
the high cell membrane penetration, such micelles effectively delivered
DOX into tumor cells (Fig. 7B). On this basis, vitamin B12 was further
conjugated on sericin molecules to enhance the targeting capability of
micelle for CD320-overexpressed gastric cancer cells [170].
Given the abundant acidic and basic amino acids, sericin qualifies as
a unique pH-sensitive material to construct “smart” nanocarriers. For
instance, a pH-responsive charge reversal sericin/chitosan nanoparticle
(SSC@NP) was prepared by crosslinking negatively-charged sericin with
positively-charged chitosan [30]. This nanoparticle exhibited a negative

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J. Liu et al.
Fig. 8. Preparation and applications of sericin-based microstructures. (A) The sericin microspheres were synthesized by an emulsification method for sustained
release of DOX, which were used for the treatment of metastatic lung cancer by pulmonary administration [189]. (B) Preparation process and morphology control of
sericin-based microparticles [186]. (C) Fabrication of microstructures using sericin lithography, and fluorescence images of osteoblasts proliferated on sericin
scaffolds with selective patterning [190].
charge in the neutral condition, while the surface charge converted to be
positive under acidic condition (pH 6.0) due to the increased amino/­
carboxyl ratio. Owing to this charge reversal property, SSC@NP signif­
icantly increased cellular internalization under tumor acidic condition
by 6.0-fold compared with the neutral environment, and sufficiently
delivered DOX into cancer cells (Fig. 7C) [30]. Similarly, a pH-sensitive
charge-reversal fluorinated graphene oxide was prepared by modifying
cationic polymer (polyethyleneimine) and sericin, which could shift the
surface charge in response to environmental pH values for promoting
circulation stability and enhancing intracellular drug delivery [162]. In
addition to adjusting the ratio of acidic and basic amino acids to achieve
pH responsiveness, abundant modifiable functional groups of sericin can
also be employed to introduce pH-sensitive properties [165,172]. For
instance, we grafted DOX to sericin molecules through the hydrazone
bonds to generate a pH-sensitive sericin-drug conjugate, which could
release DOX in acidic lysosomes [172].
In addition to serving as drug carriers, sericin is also used as a bio­
mineralized matrix or reducing agent for generating sericin/inorganic
nanocomposites [173–176]. For instance, sericin was used as a template
to mediate the nucleation of hydroxyapatite crystals [127]. Similarly,
the self-assembled sericin nanofibers were used as templates to regulate
silica nucleation and assembly for preparing nano-silica drug carriers
[174]. As a reducing agent, sericin was used to synthesize silver nano­
particles (AgNPs), which simultaneously served as a stabilizer [173]
(Fig. 7D). Interestingly, the reducing activity of sericin varies with
different origins of cocoons. Sericin derived from non-mulberry silk­
worms exhibits higher reducing activity than that from mulberry silk­
worms, which is beneficial to AgNPs formation [175]. This simple
synthesis strategy requires neither additional reducing agents nor
excessive heat treatments, that is an economical and environmentally
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Biomaterials 287 (2022) 121638
friendly method.
3.2.2. Microparticles
To enable topical drug delivery in certain tissues or organs with
special structures, and deliver larger particles (or cells), sericin micro­
particles are developed as an effective supplement to the drug delivery
systems. Various methods are utilized for fabricating sericin-based mi­
croparticles [185–189].
For treating metastatic lung cancer, our group prepared sericin mi­
croparticles (SMPs) using a water-in-oil (w/o) emulsification method,
followed by DOX loading and coating with tannic acid (TA)/ferric irons
(Fe3+) based metal-organic networks (Fig. 8A). These reasonably
designed microparticles could be effectively deposited in lungs and
remain for more than 5 days through pulmonary administration in vivo,
and continuously release anticancer drugs in a pH-dependent manner.
The DOX-loaded microparticles (DOX@SMP-MON) significantly
reduced the number of metastatic nodules in lungs in the metastatic
breast cancer (4T1) model [189].
A one-step green route to fabricate sericin-based microcapsules
without the aid of organic solvents was reported as well (Fig. 8B) [186].
The sericin aqueous solution (1% wt) was mixed with certain volumes of
CaCl2 solution (0.2 M) and stirred at 37 ◦ C for 24 h at pH 7.4. The sericin
conformation was changed through chelation of Ca ions, resulting in
microcapsules formation by self-assembly. The morphology of micro­
capsules could be easily regulated to form bionic structures (discoidal,
biconcave, cocoon-like, and tubular structures) by adjusting the con­
centration of calcium ions and stirring speed [186]. In addition, the pH
values of buffers and the types of ions could also affect the assembly of
sericin microspheres [188]. In another work, the 2-isocyanatoethyl
methacrylate (IEM) modified sericin has been synthesized for
J. Liu et al.
Fig. 9. Prospects of exploration and applications of silk sericin.
preparing a photo-crosslinkable sericin photoresist (Fig. 8C). Through
photolithography, it was easy to precisely control the sericin cross­
linking to customize the specific spatial morphology and complex
patterning of microstructures. These high-resolution microstructures
could be used as a suitable substrate for cell culture and guide cells to
grow in a particular direction without additional adhesion ligands
[190].
Transplanted cells for tissue engineering are usually vulnerable to
the host immune system and exhibit a very low proliferation rate. To
address this problem, Nayak et al. prepared the microcapsules composed
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Biomaterials 287 (2022) 121638
of sericin-alginate beads (inner core) and chitosan (outer shell) via
ionotropic gelation [191]. The microcapsules prevented graft rejection
by isolating the immune environment of the host. Meanwhile, the
porous structures of microcapsules allowed nutrient exchange, ensuring
the survival and biological metabolism of liver cells in the capsules. This
microcapsule-based cell therapy strategy is expected to generate an
enriched population of metabolically and functionally active cells for
hepatocytes transplantation in acute liver failure without the addition of
immunosuppressants.
J. Liu et al.
4. Perspectives
With recent advances and the development of sericin-based bio­
materials for tissue engineering and regeneration medicine, sericin, the
by-product of silk industry, begins to show great potential in biomedical
research and applications. The relevant developments may change the
current status of silk industry and promote the transformation and
modernization of traditional industries as well as tissue engineering and
regeneration medicine.
Although plenty of silk sericin-derived biomaterials (from nano-size
to bulk) have been developed and investigated, no sericin-derived
medical products were available on the market until now. On the con­
trary, the silk fibroin, which also originates from silk cocoons, has been
manufactured to be commercialized medical products for different
application scenarios (e.g., SERI® surgical scaffold, Sofsilk™ Silk Su­
tures, Silk Voice®, Sidaiyi® wound dressing). After comparing the two
proteins from silkworm cocoons, we speculate the following issues that
may hinder the development and clinical translation of sericin
biomaterials:
(1) Silk sericin has been regarded as the waste of textile industry for
thousands of years, which leads to significantly less attention to
sericin compared with fibroin. Moreover, the long-term misun­
derstanding of sericin’s immunogenicity had hindered the
development and application of sericin-based biomaterials. As a
result, the studies on sericin are far less than those on fibroin,
including the structure characterization, exploration of biological
activities, and product development.
(2) It is a challenge to obtain sericin protein with high quality
(without degradation and denaturation) on a large or industrial
scale. Although we have dissolved and isolated the intact sericin
protein from the fibroin-deficient silkworm cocoons using a mild
extraction method, the resources of mutant silkworm cocoons are
quite limited. For the wild-type silkworm cocoons, including both
mulberry and non-mulberry categories, all the extraction pro­
cesses would induce unfavorable degradation and denaturation
of sericin protein. This issue dramatically limits the in-depth
studies on sericin properties and fabrication of sericin-based
biomaterials.
(3) The immunogenicity of sericin has long been controversial,
although many studies indicated it to be a safe and suitable
biomaterial. Recently, we have investigated the biocompatibility
of sericin derived from wild-type and fibroin-deficient mutant
silkworm cocoons (B. mori) in BALB/c mice, and demonstrated
the low immunogenicity and allergenicity. However, this study
only focused on the mulberry silkworm cocoons and tested the
immune responses in mice. Thus, the biocompatibility of
different types of silkworm cocoons should be further studied,
and the immune responses of sericin in other animals or even
humans need to be examined.
(4) The underlying mechanisms of sericin promoting tissue repair are
not clear. In our previous work, we explored the mechanism of
sericin in stimulating angiogenesis and found that sericin
enhanced vascular endothelial growth factor-a (VEGFa) expres­
sion via activating extracellular regulated protein kinases (ERK)
phosphorylation [115]. According to the RNA sequencing,
sericin-based scaffold has been demonstrated to induce BMSCs
migration and osteogenesis differentiation via activating
mitogen-activated protein kinases (MAPK), tumor necrosis factor
(TNF), and chemokine signaling pathways, thereby improving
bone regeneration [123]. However, we did not identify the spe­
cific peptide sequence on sericin that activates these signaling
and pathways. Since sericin is a mixture of multiple proteins (or
peptides) and the extraction procedures cleave these proteins, it
is difficult to identify the specific receptors and related signal
pathways until every single fragment could be isolated.
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Biomaterials 287 (2022) 121638
(5) The sericin contains a large number of random coils in the
structure that would increase the brittleness of sericin-based
materials [16]. Besides, the harsh physical/chemical extraction
methods further decrease the molecular weights of isolated
peptides, which further results in defective properties [16,34,48].
Thus, the sericin biomaterials usually suffer from poor mechan­
ical properties.
According to FDA’s classification management rules for medical
devices, it is essential to demonstrate the substantial equivalence of new
medical devices to a predicate device (a legally marketed one), including
the safety and effectiveness. But as aforementioned, there are various
challenges in the development of sericin-derived products, such as the
biosafety, efficacy, mechanical property, and batch difference. To
address these issues, great research efforts on sericin need to be directed
towards (1) the development of novel sericin extraction techniques that
could efficiently isolate sericin from silkworm cocoons (both wild-type
and mutant cocoons) with minimized degradation and denaturation;
(2) identification of peptide sequences and conformation of sericin; (3)
active preclinical and clinical studies on the biosafety and effectiveness
of sericin and sericin-based formulations; (4) in-depth mechanism
exploration on the bioactivities of sericin and its derived peptides; and
(5) enhancement of the mechanical properties of sericin-based
materials.
Of note, among these sericin-based materials summarized in this
review, the wearable electronic devices generated by sericin could
conventionally monitor personal healthcare, such as human movement,
skin temperature, and sweat loss. These devices could be directly
attached to human skin or clothes avoiding the safety concerns of
sericin, which may be easier for translation or commercialization.
Overall, despite some “uncultivated lands” on sericin investigation,
such natural protein exhibits great potential for the generation of novel
materials for tissue engineering and regeneration medicine. In the
future, it is encouraged to develop sericin-based materials with intelli­
gent responsiveness and on-demand maneuverability, which may be one
of the promising research directions for sericin materials. In addition,
different forms of materials based on sericin, such as the “inks” for 3D
printing [192], microneedles [193], wearable electronic devices, and
even smart micro/nano robots can be developed for various biomedical
applications (Fig. 9). The applications of sericin in these interdisci­
plinary fields are also worth exploring.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Acknowledgments
This work was supported by the National Natural Science Foundation
of China [82072167, 81873931, 82072068, and 81974382]; the Joint
Fund of Ministry of Education for Equipment Pre-research
[6141A02022626], the Major Scientific and Technological Innovation
Projects in Hubei Province [2018ACA136], the Integrated Innovative
Team for Major Human Diseases Program of Tongji Medical College of
HUST, the Academic Doctor Supporting Program of Tongji Medical
College of HUST, and the Union Hospital Foundation for Young Scientist
(2021xhqh01).
References
[1] S. Blake, N.Y. Kim, N. Kong, J. Ouyang, W. Tao, Silk’s cancer applications as a
biodegradable material, Mater. Today Sustain. 13 (2021), 100069, https://doi.
org/10.1016/j.mtsust.2021.100069.
J. Liu et al.
[2] W. Huang, S. Ling, C. Li, F.G. Omenetto, D.L. Kaplan, Silkworm silk-based
materials and devices generated using bio-nanotechnology, Chem. Soc. Rev. 47
(17) (2018) 6486–6504, https://doi.org/10.1039/C8CS00187A.
[3] C. Holland, K. Numata, J. Rnjak-Kovacina, F.P. Seib, The biomedical use of silk:
past, present, future, Adv. Healthc. Mater. 8 (1) (2019), e1800465, https://doi.
org/10.1002/adhm.201800465.
[4] F.G. Omenetto, D.L. Kaplan, New opportunities for an ancient material, Science
329 (5991) (2010) 528–531, https://doi.org/10.1126/science.1188936.
[5] Y. Wang, H.J. Kim, G. Vunjak-Novakovic, D.L. Kaplan, Stem cell-based tissue
engineering with silk biomaterials, Biomaterials 27 (36) (2006) 6064–6082,
https://doi.org/10.1016/j.biomaterials.2006.07.008.
[6] B. Kundu, R. Rajkhowa, S.C. Kundu, X. Wang, Silk fibroin biomaterials for tissue
regenerations, Adv. Drug Deliv. Rev. 65 (4) (2013) 457–470, https://doi.org/
10.1016/j.addr.2012.09.043.
[7] M. Gholipourmalekabadi, S. Sapru, A. Samadikuchaksaraei, R.L. Reis, D.
L. Kaplan, S.C. Kundu, Silk fibroin for skin injury repair: where do things stand?
Adv. Drug Deliv. Rev. 153 (2020) 28–53, https://doi.org/10.1016/j.
addr.2019.09.003.
[8] P.W. Madden, I. Klyubin, M.J. Ahearne, Silk fibroin safety in the eye: a review
that highlights a concern, BMJ Open Ophthalmol. 5 (1) (2020), e000510, https://
doi.org/10.1136/bmjophth-2020-000510.
[9] P. Aramwit, T. Siritientong, T. Srichana, Potential applications of silk sericin, a
natural protein from textile industry by-products, Waste Manag. Res. 30 (3)
(2012) 217–224, https://doi.org/10.1177/0734242X11404733.
[10] P. Aramwit, S. Kanokpanont, T. Nakpheng, T. Srichana, The effect of sericin from
various extraction methods on cell viability and collagen production, Int. J. Mol.
Sci. 11 (5) (2010) 2200–2211, https://doi.org/10.3390/ijms11052200.
[11] S. Nayak, T. Dey, D. Naskar, S.C. Kundu, The promotion of osseointegration of
titanium surfaces by coating with silk protein sericin, Biomaterials 34 (12) (2013)
2855–2864, https://doi.org/10.1016/j.biomaterials.2013.01.019.
[12] J.R. Eidet, S. Reppe, L. Pasovic, O.K. Olstad, T. Lyberg, A.Z. Khan, I.G. Fostad, D.
F. Chen, T.P. Utheim, The silk-protein sericin induces rapid melanization of
cultured primary human retinal pigment epithelial cells by activating the NF-κB
pathway, Sci. Rep. 6 (2016), 22671, https://doi.org/10.1038/srep22671.
[13] L. Pasovic, T.P. Utheim, S. Reppe, A.Z. Khan, C.J. Jackson, B. Thiede, J.P. Berg, E.
B. Messelt, J.R. Eidet, Improvement of storage medium for cultured human retinal
pigment epithelial cells using factorial design, Sci. Rep. 8 (1) (2018) 5688,
https://doi.org/10.1038/s41598-018-24121-8.
[14] N. Kato, S. Sato, A. Yamanaka, H. Yamada, N. Fuwa, M. Nomura, Silk protein,
sericin, inhibits lipid peroxidation and tyrosinase activity, Biosci., Biotechnol.,
Biochem. 62 (1) (1998) 145–147, https://doi.org/10.1271/bbb.62.145.
[15] K. Jena, J.P. Pandey, R. Kumari, A.K. Sinha, V.P. Gupta, G.P. Singh, Free radical
scavenging potential of sericin obtained from various ecoraces of tasar cocoons
and its cosmeceuticals implication, Int. J. Biol. Macromol. 120 (Pt A) (2018)
255–262, https://doi.org/10.1016/j.ijbiomac.2018.08.090.
[16] L. Lamboni, M. Gauthier, G. Yang, Q. Wang, Silk sericin: a versatile material for
tissue engineering and drug delivery, Biotechnol. Adv. 33 (8) (2015) 1855–1867,
https://doi.org/10.1016/j.biotechadv.2015.10.014.
[17] R.I. Kunz, R.M. Brancalhao, L.F. Ribeiro, M.R. Natali, Silkworm sericin: properties
and biomedical applications, BioMed Res. Int. 2016 (2016), 8175701, https://
doi.org/10.1155/2016/8175701.
[18] Z. Wang, J. Wang, Y. Jin, Z. Luo, W. Yang, H. Xie, K. Huang, L. Wang,
A neuroprotective sericin hydrogel as an effective neuronal cell carrier for the
repair of ischemic stroke, ACS Appl. Mater. Interfaces 7 (44) (2015)
24629–24640, https://doi.org/10.1021/acsami.5b06804.
[19] C. Qi, J. Liu, Y. Jin, L. Xu, G. Wang, Z. Wang, L. Wang, Photo-crosslinkable,
injectable sericin hydrogel as 3D biomimetic extracellular matrix for minimally
invasive repairing cartilage, Biomaterials 163 (2018) 89–104, https://doi.org/
10.1016/j.biomaterials.2018.02.016.
[20] S. Tyeb, N. Kumar, A. Kumar, V. Verma, Flexible agar-sericin hydrogel film
dressing for chronic wounds, Carbohydr. Polym. 200 (2018) 572–582, https://
doi.org/10.1016/j.carbpol.2018.08.030.
[21] L. Ai, Y. Wang, G. Tao, P. Zhao, A. Umar, P. Wang, H. He, Polydopamine-based
surface modification of ZnO nanoparticles on sericin/polyvinyl alcohol composite
film for antibacterial application, Molecules 24 (3) (2019) 503, https://doi.org/
10.3390/molecules24030503.
[22] H. Xie, W. Yang, J. Chen, J. Zhang, X. Lu, X. Zhao, K. Huang, H. Li, P. Chang,
Z. Wang, L. Wang, A silk sericin/silicone nerve guidance conduit promotes
regeneration of a transected sciatic nerve, Adv. Healthc. Mater. 4 (15) (2015)
2195–2205, https://doi.org/10.1002/adhm.201500355.
[23] J. Rao, Y. Cheng, Y. Liu, Z. Ye, B. Zhan, D. Quan, Y. Xu, A multi-walled silk
fibroin/silk sericin nerve conduit coated with poly(lactic-co-glycolic acid) sheath
for peripheral nerve regeneration, Mater. Sci. Eng., C 73 (2017) 319–332, https://
doi.org/10.1016/j.msec.2016.12.085.
[24] L. Zhang, W. Yang, H. Xie, H. Wang, J. Wang, Q. Su, X. Li, Y. Song, G. Wang,
L. Wang, Z. Wang, Sericin nerve guidance conduit delivering therapeutically
repurposed clobetasol for functional and structural regeneration of transected
peripheral nerves, ACS Biomater. Sci. Eng. 5 (3) (2019) 1426–1439, https://doi.
org/10.1021/acsbiomaterials.8b01297.
[25] X. Li, W. Yang, H. Xie, J. Wang, L. Zhang, Z. Wang, L. Wang, CNT/Sericin
conductive nerve guidance conduit promotes functional recovery of transected
peripheral nerve injury in a rat model, ACS Appl. Mater. Interfaces 12 (33) (2020)
36860–36872, https://doi.org/10.1021/acsami.0c08457.
[26] Z. Karahaliloglu, E. Kilicay, E.B. Denkbas, Antibacterial chitosan/silk sericin 3D
porous scaffolds as a wound dressing material, Artif. Cell Nanomed. Biotechnol.
45 (6) (2017) 1–14, https://doi.org/10.1080/21691401.2016.1203796.
15
Biomaterials 287 (2022) 121638
[27] L. Zhang, W. Yang, K. Tao, Y. Song, H. Xie, J. Wang, X. Li, X. Shuai, J. Gao,
P. Chang, G. Wang, Z. Wang, L. Wang, Sustained local release of NGF from a
chitosan-sericin composite scaffold for treating chronic nerve compression, ACS
Appl. Mater. Interfaces 9 (4) (2017) 3432–3444, https://doi.org/10.1021/
acsami.6b14691.
[28] L. Lamboni, C. Xu, J. Clasohm, J. Yang, M. Saumer, K.H. Schafer, G. Yang, Silk
sericin-enhanced microstructured bacterial cellulose as tissue engineering
scaffold towards prospective gut repair, Mater. Sci. Eng., C 102 (2019) 502–510,
https://doi.org/10.1016/j.msec.2019.04.043.
[29] G. Das, H.S. Shin, E.V.R. Campos, L.F. Fraceto, M. Del Pilar Rodriguez-Torres, K.
C.F. Mariano, D.R. de Araujo, F. Fernandez-Luqueno, R. Grillo, J.K. Patra, Sericin
based nanoformulations: a comprehensive review on molecular mechanisms of
interaction with organisms to biological applications, J. Nanobiotechnol. 19 (1)
(2021) 30, https://doi.org/10.1186/s12951-021-00774-y.
[30] D. Hu, Z. Xu, Z. Hu, B. Hu, M. Yang, L. Zhu, pH-Triggered charge-reversal silk
sericin-based nanoparticles for enhanced cellular uptake and doxorubicin
delivery, ACS Sustainable Chem. Eng. 5 (2) (2017) 1638–1647, https://doi.org/
10.1021/acssuschemeng.6b02392.
[31] G.H. Altman, F. Diaz, C. Jakuba, T. Calabro, R.L. Horan, J. Chen, H. Lu,
J. Richmond, D.L. Kaplan, Silk-based biomaterials, Biomaterials 24 (3) (2003)
401–416, https://doi.org/10.1016/s0142-9612(02)00353-8.
[32] R. Konwarh, B.K. Bhunia, B.B. Mandal, Opportunities and challenges in exploring
Indian non-mulberry silk for biomedical applications, Proc. Indian Natl. Sci.
Acad. 83 (1) (2017) 85–101, https://doi.org/10.16943/ptinsa/2017/41288.
[33] R. Dash, M. Mandal, S.K. Ghosh, S.C. Kundu, Silk sericin protein of tropical tasar
silkworm inhibits UVB-induced apoptosis in human skin keratinocytes, Mol. Cell.
Biochem. 311 (1–2) (2008) 111–119, https://doi.org/10.1007/s11010-008-
9702-z.
[34] B. Kundu, N.E. Kurland, V.K. Yadavalli, S.C. Kundu, Isolation and processing of
silk proteins for biomedical applications, Int. J. Biol. Macromol. 70 (2014) 70–77,
https://doi.org/10.1016/j.ijbiomac.2014.06.022.
[35] T.T. Cao, Y.Q. Zhang, Processing and characterization of silk sericin from Bombyx
mori and its application in biomaterials and biomedicines, Mater. Sci. Eng., C 61
(2016) 940–952, https://doi.org/10.1016/j.msec.2015.12.082.
[36] E. Bari, S. Perteghella, S. Farago, M.L. Torre, Association of silk sericin and
platelet lysate: premises for the formulation of wound healing active medications,
Int. J. Biol. Macromol. 119 (2018) 37–47, https://doi.org/10.1016/j.
ijbiomac.2018.07.142.
[37] Y.J. Wang, Y.Q. Zhag, Three-layered sericins around the silk fibroin fiber from
Bombyx mori cocoon and their amino acid composition, Adv. Mater. Res.
175–176 (2011) 158–163. https://dx.doi.org/10.4028/www.scientific.net/AMR.
175-176.158.
[38] Z. Wang, Y. Zhang, J. Zhang, L. Huang, J. Liu, Y. Li, G. Zhang, S.C. Kundu,
L. Wang, Exploring natural silk protein sericin for regenerative medicine: an
injectable, photoluminescent, cell-adhesive 3D hydrogel, Sci. Rep. 4 (2014) 7064,
https://doi.org/10.1038/srep07064.
[39] J. Liu, C. Qi, K. Tao, J. Zhang, J. Zhang, L. Xu, X. Jiang, Y. Zhang, L. Huang, Q. Li,
H. Xie, J. Gao, X. Shuai, G. Wang, Z. Wang, L. Wang, Sericin/dextran injectable
hydrogel as an optically trackable drug delivery system for malignant melanoma
treatment, ACS Appl. Mater. Interfaces 8 (10) (2016) 6411–6422, https://doi.
org/10.1021/acsami.6b00959.
[40] Y.N. Jo, B.D. Park, I.C. Um, Effect of storage and drying temperature on the
gelation behavior and structural characteristics of sericin, Int. J. Biol. Macromol.
81 (2015) 936–941, https://doi.org/10.1016/j.ijbiomac.2015.09.016.
[41] H. Teramoto, M. Miyazawa, Analysis of structural properties and formation of
Sericin fiber by infrared spectroscopy, J. Insect Biotechnol. Sericol. 72 (3) (2003)
157–162, https://doi.org/10.11416/jibs.72.157.
[42] S. Nayak, S. Talukdar, S.C. Kundu, Potential of 2D crosslinked sericin membranes
with improved biostability for skin tissue engineering, Cell Tissue Res. 347 (3)
(2012) 783–794, https://doi.org/10.1007/s00441-011-1269-4.
[43] M. Yuksek, D. Kocak, A. Beyit, N.J.A.i.E.B. Merdan, Effect of degumming
performed with different type natural soaps and through ultrasonic method on
the properties of silk fiber, Adv. Environ. Biol. 6 (2) (2012) 801–808.
[44] D. Gupta, A. Agrawal, H. Chaudhary, M. Gulrajani, C. Gupta, Cleaner process for
extraction of sericin using infrared, J. Clean. Prod. 52 (2013) 488–494, https://
doi.org/10.1016/j.jclepro.2013.03.016.
[45] A. Kurioka, F. Kurioka, M. Yamazaki, Characterization of sericin powder prepared
from citric acid-degraded sericin polypeptides of the silkworm, Bombyx Mori,
Biosci. Biotechnol. Biochem. 68 (4) (2004) 774–780, https://doi.org/10.1271/
bbb.68.774.
[46] G. Freddi, G. Allara, G.J.C.T. Candiani, Degumming of silk fabrics with tartaric
acid, J. Soc. Dye. Colour. 112 (7–8) (2010) 191–195, https://doi.org/10.1111/
j.1478-4408.1996.tb01817.x.
[47] N.M. Mahmoodi, M. Arami, F. Mazaheri, S. Rahimi, Degradation of sericin
(degumming) of Persian silk by ultrasound and enzymes as a cleaner and
environmentally friendly process, J. Clean. Prod. 18 (2) (2010) 146–151, https://
doi.org/10.1016/j.jclepro.2009.10.003.
[48] H. Yun, H. Oh, M.K. Kim, H.W. Kwak, J.Y. Lee, I.C. Um, S.K. Vootla, K.H. Lee,
Extraction conditions of Antheraea mylitta sericin with high yields and minimum
molecular weight degradation, Int. J. Biol. Macromol. 52 (2013) 59–65, https://
doi.org/10.1016/j.ijbiomac.2012.09.017.
[49] W. Lamoolphak, W. De-Eknamkul, A. Shotipruk, Hydrothermal production and
characterization of protein and amino acids from silk waste, Bioresour. Technol.
99 (16) (2008) 7678–7685, https://doi.org/10.1016/j.biortech.2008.01.072.
J. Liu et al.
[50] K.U. Sprague, The Bombyx mori silk proteins: characterization of large
polypeptides, Biochemistry 14 (5) (1975) 925–931, https://doi.org/10.1021/
bi00676a008.
[51] B.C. Dash, B.B. Mandal, S.C. Kundu, Silk gland sericin protein membranes:
fabrication and characterization for potential biotechnological applications,
J. Biotechnol. 144 (4) (2009) 321–329, https://doi.org/10.1016/j.
jbiotec.2009.09.019.
[52] P. Aramwit, S. Damrongsakkul, S. Kanokpanont, T. Srichana, Properties and
antityrosinase activity of sericin from various extraction methods, Biotechnol.
Appl. Biochem. 55 (2) (2010) 91–98, https://doi.org/10.1042/BA20090186.
[53] S.G. Kim, H. Kweon, Y.Y. Jo, Toll-like receptor and silk sericin for tissue
engineering, Int. J. Ind. Entomol. 42 (1) (2021) 1–6, https://doi.org/10.7852/
ijie.2021.42.1.1.
[54] Y.Y. Jo, H. Kweon, D.W. Kim, K. Baek, W.S. Chae, Y.J. Kang, J.H. Oh, S.G. Kim,
U. Garagiola, Silk sericin application increases bone morphogenic protein-2/4
expression via a toll-like receptor-mediated pathway, Int. J. Biol. Macromol. 190
(2021) 607–617, https://doi.org/10.1016/j.ijbiomac.2021.09.021.
[55] Y. Li, Y. Huang, P. Pan, X. Che, Y. Zhang, Y. Zhang, A. Amal, X. Li, W. Niu, N. Luo,
W. Zhang, D. Gao, Q. Tan, Q. Zhang, X. Xing, Z. Luo, J. Wu, Sericin and sericin-
derived peptide alleviate viral pathogenesis in mice though inhibiting lactate
production and facilitating antiviral response, Appl. Mater. Today 25 (2021),
https://doi.org/10.1016/j.apmt.2021.101256.
[56] W.H. Wang, W.S. Lin, C.H. Shih, C.Y. Chen, S.H. Kuo, W.L. Li, Y.S. Lin,
Functionality of silk cocoon (Bombyx mori L.) sericin extracts obtained through
high-temperature hydrothermal method, Materials 14 (18) (2021), https://doi.
org/10.3390/ma14185314.
[57] C. Bungthong, S. Siriamornpun, Changes in amino acid profiles and bioactive
compounds of Thai silk cocoons as affected by water extraction, Molecules 26 (7)
(2021), https://doi.org/10.3390/molecules26072033.
[58] F. Wang, T.T. Cao, Y.Q. Zhang, Effect of silk protein surfactant on silk degumming
and its properties, Mater. Sci. Eng., C 55 (2015) 131–136, https://doi.org/
10.1016/j.msec.2015.05.041.
[59] F. Wang, Y.Q. Zhang, Effects of alkyl polyglycoside (APG) on Bombyx mori silk
degumming and the mechanical properties of silk fibroin fibre, Mater. Sci. Eng., C
74 (2017) 152–158, https://doi.org/10.1016/j.msec.2017.02.015.
[60] S. Cherdchom, A. Sereemaspun, P. Aramwit, Urea-extracted sericin is potentially
better than kojic acid in the inhibition of melanogenesis through increased
reactive oxygen species generation, J. Tradit. Complement. Med. 11 (6) (2021)
570–580, https://doi.org/10.1016/j.jtcme.2021.06.005.
[61] Y. Takasu, H. Yamada, K. Tsubouchi, Isolation of three main sericin components
from the cocoon of the silkworm, Bombyx mori, Biosci. Biotechnol. Biochem. 66
(12) (2002) 2715–2718, https://doi.org/10.1271/bbb.66.2715.
[62] M.M. Ali, S.B. Arumugam, Effect of crude extract of Bombyx mori coccoons in
hyperlipidemia and atherosclerosis, J. Ayurveda Integr. Med. 2 (2) (2011) 72–78,
https://doi.org/10.4103/0975-9476.82527.
[63] G. Freddi, R. Mossotti, R. Innocenti, Degumming of silk fabric with several
proteases, J. Biotechnol. 106 (1) (2003) 101–112, https://doi.org/10.1016/j.
jbiotec.2003.09.006.
[64] S.J. Eom, N.H. Lee, M.C. Kang, Y.H. Kim, T.G. Lim, K.M. Song, Silk peptide
production from whole silkworm cocoon using ultrasound and enzymatic
treatment and its suppression of solar ultraviolet-induced skin inflammation,
Ultrason. Sonochem. 61 (2020), 104803, https://doi.org/10.1016/j.
ultsonch.2019.104803.
[65] L. Zhu, J. Lin, L. Pei, Y. Luo, D. Li, Z. Huang, Recent advances in environmentally
friendly and green degumming processes of silk for textile and non-textile
applications, Polymers 14 (4) (2022), https://doi.org/10.3390/polym14040659.
[66] S. Franz, S. Rammelt, D. Scharnweber, J.C. Simon, Immune responses to implants
- a review of the implications for the design of immunomodulatory biomaterials,
Biomaterials 32 (28) (2011) 6692–6709, https://doi.org/10.1016/j.
biomaterials.2011.05.078.
[67] B.N. Brown, S.F. Badylak, Expanded applications, shifting paradigms and an
improved understanding of host-biomaterial interactions, Acta Biomater. 9 (2)
(2013) 4948–4955, https://doi.org/10.1016/j.actbio.2012.10.025.
[68] C.G. Uragoda, P.N. Wijekoon, Asthma in silk workers, J. Soc. Occup. Med. 41 (3)
(1991) 140–142, https://doi.org/10.1093/occmed/41.3.140.
[69] J.C. Celedon, L.J. Palmer, X. Xu, B. Wang, Z. Fang, S.T. Weiss, Sensitization to silk
and childhood asthma in rural China, Pediatrics 107 (5) (2001) E80, https://doi.
org/10.1542/peds.107.5.e80.
[70] S. Das, G. Natarajan, Silk fiber composites in biomedical applications, Mater.
Biomed. Eng. (2019) 309–338, https://doi.org/10.1016/B978-0-12-816872-
1.00011-X.
[71] D. Chouhan, B.B. Mandal, Silk biomaterials in wound healing and skin
regeneration therapeutics: from bench to bedside, Acta Biomater. 103 (2020)
24–51, https://doi.org/10.1016/j.actbio.2019.11.050.
[72] A.Z. Siavashani, J. Mohammadi, M. Rottmar, B. Senturk, J. Nourmohammadi,
B. Sadeghi, L. Huber, K. Maniura-Weber, Silk fibroin/sericin 3D sponges: the
effect of sericin on structural and biological properties of fibroin, Int. J. Biol.
Macromol. 153 (2020) 317–326, https://doi.org/10.1016/j.
ijbiomac.2020.02.316.
[73] B.O. Ode Boni, B.M. Bakadia, A.R. Osi, Z. Shi, H. Chen, M. Gauthier, G. Yang,
Immune response to silk sericin-fibroin composites: potential immunogenic
elements and alternatives for immunomodulation, Macromol. Biosci. 22 (1)
(2022), e2100292, https://doi.org/10.1002/mabi.202100292.
[74] B.B. Mandal, A.S. Priya, S.C. Kundu, Novel silk sericin/gelatin 3-D scaffolds and
2-D films: fabrication and characterization for potential tissue engineering
16
Biomaterials 287 (2022) 121638
applications, Acta Biomater. 5 (8) (2009) 3007–3020, https://doi.org/10.1016/j.
actbio.2009.03.026.
[75] B. Panilaitis, G.H. Altman, J. Chen, H.J. Jin, V. Karageorgiou, D.L. Kaplan,
Macrophage responses to silk, Biomaterials 24 (18) (2003) 3079–3085, https://
doi.org/10.1016/s0142-9612(03)00158-3.
[76] Y.Q. Zhang, Y. Ma, Y.Y. Xia, W.D. Shen, J.P. Mao, R.Y. Xue, Silk sericin-insulin
bioconjugates: synthesis, characterization and biological activity, J. Contr.
Release 115 (3) (2006) 307–315, https://doi.org/10.1016/j.jconrel.2006.08.019.
[77] Z. Jiao, Y. Song, Y. Jin, C. Zhang, D. Peng, Z. Chen, P. Chang, S.C. Kundu,
G. Wang, Z. Wang, L. Wang, In vivo characterizations of the immune properties of
sericin: an ancient material with emerging value in biomedical applications,
Macromol. Biosci. 17 (12) (2017), https://doi.org/10.1002/mabi.201700229.
[78] S. Terada, T. Nishimura, M. Sasaki, H. Yamada, M. Miki, Sericin, a protein derived
from silkworms, accelerates the proliferation of several mammalian cell lines
including a hybridoma, Cytotechnology 40 (1–3) (2002) 3–12, https://doi.org/
10.1023/A:1023993400608.
[79] S. Terada, M. Sasaki, K. Yanagihara, H. Yamada, Preparation of silk protein
sericin as mitogenic factor for better mammalian cell culture, J. Biosci. Bioeng.
100 (6) (2005) 667–671, https://doi.org/10.1263/jbb.100.667.
[80] K. Thitinan, M. Pannamas, L.J.J.o.A.S. Natthanej, In-vitro characterization of silk
sericin as an anti-aging agent, J. Agric. Sci. 5 (3) (2013) 13–28, https://doi.org/
10.5539/jas.v5n3p54.
[81] A. Ogawa, S. Terada, M. Miki, T. Kimura, A. Yamaguchi, M. Sasaki, H. Yamada,
Supplementation of Sericin Is Effective in Maintenance of Islet Survival and
Function under Serum-free Culture, Springer Netherlands, Dordrecht, 2006,
pp. 107–112, https://doi.org/10.1007/1-4020-4457-7_15.
[82] A. Veiga, F. Castro, C.C. Reis, A. Sousa, A.L. Oliveira, F. Rocha, Hydroxyapatite/
sericin composites: a simple synthesis route under near-physiological conditions
of temperature and pH and preliminary study of the effect of sericin on the
biomineralization process, Mater. Sci. Eng., C 108 (2020), 110400, https://doi.
org/10.1016/j.msec.2019.110400.
[83] S. Dinescu, B. Galateanu, M. Albu, A. Cimpean, A. Dinischiotu, M. Costache,
Sericin enhances the bioperformance of collagen-based matrices preseeded with
human-adipose derived stem cells (hADSCs), Int. J. Mol. Sci. 14 (1) (2013)
1870–1889, https://doi.org/10.3390/ijms14011870.
[84] S. Tyeb, P.A. Shiekh, V. Verma, A. Kumar, Adipose-derived stem cells (ADSCs)
loaded gelatin-sericin-laminin cryogels for tissue regeneration in diabetic
wounds, Biomacromolecules 21 (2) (2020) 294–304, https://doi.org/10.1021/
acs.biomac.9b01355.
[85] S. Sapru, S. Das, M. Mandal, A.K. Ghosh, S.C. Kundu, Nonmulberry silk protein
sericin blend hydrogels for skin tissue regeneration - in vitro and in vivo, Int. J.
Biol. Macromol. 137 (2019) 545–553, https://doi.org/10.1016/j.
ijbiomac.2019.06.121.
[86] N. Nagai, Y. Fukuoka, M. Ishii, H. Otake, T. Yamamoto, A. Taga, N. Okamoto,
Y. Shimomura, Instillation of sericin enhances corneal wound healing through the
ERK pathway in rat debrided corneal epithelium, Int. J. Mol. Sci. 19 (4) (2018)
1123, https://doi.org/10.3390/ijms19041123.
[87] M. Ersel, Y. Uyanikgil, F. Karbek Akarca, E. Ozcete, Y.A. Altunci, F. Karabey,
T. Cavusoglu, A. Meral, G. Yigitturk, E. Oyku Cetin, Effects of silk sericin on
incision wound healing in a dorsal skin flap wound healing rat model, Med. Sci.
Mon. Int. Med. J. Exp. Clin. Res. 22 (2016) 1064–1078, https://doi.org/
10.12659/msm.897981.
[88] X. Dong, S.X. Zhao, X.L. Yin, H.Y. Wang, Z.G. Wei, Y.Q. Zhang, Silk sericin has
significantly hypoglycaemic effect in type 2 diabetic mice via anti-oxidation and
anti-inflammation, Int. J. Biol. Macromol. 150 (2020) 1061–1071, https://doi.
org/10.1016/j.ijbiomac.2019.10.111.
[89] A. Kurioka, M. Yamazaki, Purification and identification of flavonoids from the
yellow green cocoon shell (Sasamayu) of the silkworm, Bombyx mori, Biosci.
Biotechnol. Biochem. 66 (6) (2002) 1396–1399, https://doi.org/10.1271/
bbb.66.1396.
[90] M. Schurink, W.J. van Berkel, H.J. Wichers, C.G. Boeriu, Novel peptides with
tyrosinase inhibitory activity, Peptides 28 (3) (2007) 485–495, https://doi.org/
10.1016/j.peptides.2006.11.023.
[91] T. Chlapanidas, S. Farago, G. Lucconi, S. Perteghella, M. Galuzzi, M. Mantelli, M.
A. Avanzini, M.C. Tosca, M. Marazzi, D. Vigo, M.L. Torre, M. Faustini, Sericins
exhibit ROS-scavenging, anti-tyrosinase, anti-elastase, and in vitro
immunomodulatory activities, Int. J. Biol. Macromol. 58 (2013) 47–56, https://
doi.org/10.1016/j.ijbiomac.2013.03.054.
[92] J.P. Kumar, B.B. Mandal, Antioxidant potential of mulberry and non-mulberry
silk sericin and its implications in biomedicine, Free Radic. Biol. Med. 108 (2017)
803–818, https://doi.org/10.1016/j.freeradbiomed.2017.05.002.
[93] H. Sies, Biochemie des oxidativen Stress, Angew. Chem. 98 (12) (1986)
1061–1075, https://doi.org/10.1002/ange.19860981203.
[94] J. Kaur, R. Rajkhowa, T. Tsuzuki, K. Millington, J. Zhang, X. Wang,
Photoprotection by silk cocoons, Biomacromolecules 14 (10) (2013) 3660–3667,
https://doi.org/10.1021/bm401023h.
[95] A. Rosena, T. Koobkokkruad, W. Eaknai, P. Bunwatcharaphansakun,
R. Maniratanachote, S. Aueviriyavit, Protective effect of Thai silk extracts on
drug-induced phototoxicity in human epidermal A431 cells and a reconstructed
human epidermis model, J. Photochem. Photobiol., B 188 (2018) 50–59, https://
doi.org/10.1016/j.jphotobiol.2018.08.022.
[96] T. Isobe, Y. Ikebata, T. Onitsuka, L.T. Do, Y. Sato, M. Taniguchi, T. Otoi,
Cryopreservation for bovine embryos in serum-free freezing medium containing
silk protein sericin, Cryobiology 67 (2) (2013) 184–187, https://doi.org/
10.1016/j.cryobiol.2013.06.010.
J. Liu et al.
[97] M. Hosoe, Y. Inaba, Y. Hashiyada, K. Imai, K. Kajitani, Y. Hasegawa, M. Irie,
H. Teramoto, T. Takahashi, S. Niimura, Effect of supplemented sericin on the
development, cell number, cryosurvival and number of lipid droplets in cultured
bovine embryos, Anim. Sci. J. 88 (2) (2017) 241–247, https://doi.org/10.1111/
asj.12628.
[98] P. Kumar, D. Kumar, P. Sikka, P. Singh, Sericin supplementation improves semen
freezability of buffalo bulls by minimizing oxidative stress during
cryopreservation, Anim. Reprod. Sci. 152 (2015) 26–31, https://doi.org/
10.1016/j.anireprosci.2014.11.015.
[99] T.T. Cao, Y.Q. Zhang, The potential of silk sericin protein as a serum substitute or
an additive in cell culture and cryopreservation, Amino Acids 49 (6) (2017)
1029–1039, https://doi.org/10.1007/s00726-017-2396-3.
[100] F. Aghaz, M. Khazaei, A. Vaisi-Raygani, M. Bakhtiyari, Cryoprotective effect of
sericin supplementation in freezing and thawing media on the outcome of
cryopreservation in human sperm, Aging Male 23 (5) (2020) 469–476, https://
doi.org/10.1080/13685538.2018.1529156.
[101] C. Song, D. Liu, S. Yang, L. Cheng, E. Xing, Z. Chen, Sericin enhances the insulin-
PI3K/AKT signaling pathway in the liver of a type 2 diabetes rat model, Exp. Ther.
Med. 16 (4) (2018) 3345–3352, https://doi.org/10.3892/etm.2018.6615.
[102] R.I. Kunz, A.N. Capelassi, A.C.P. Alegre-Maller, M.L. Bonfleur, L.F.C. Ribeiro, R.
M. Costa, M.R.M. Natali, Sericin as treatment of obesity: morphophysiological
effects in obese mice fed with high-fat diet, Einstein (Sao Paulo) 18 (2020),
eAO4876, https://doi.org/10.31744/einstein_journal/2020AO4876.
[103] M. Yang, N. Mandal, Y. Shuai, G. Zhou, S. Min, L. Zhu, Mineralization and
biocompatibility of Antheraea pernyi (A. pernyi) silk sericin film for potential
bone tissue engineering, Bio Med. Mater. Eng. 24 (1) (2014) 815–824, https://
doi.org/10.3233/BME-130873.
[104] O. Akturk, A. Tezcaner, H. Bilgili, M.S. Deveci, M.R. Gecit, D. Keskin, Evaluation
of sericin/collagen membranes as prospective wound dressing biomaterial,
J. Biosci. Bioeng. 112 (3) (2011) 279–288, https://doi.org/10.1016/j.
jbiosc.2011.05.014.
[105] L. Lamboni, Y. Li, J. Liu, G. Yang, Silk sericin-functionalized bacterial cellulose as
a potential wound-healing biomaterial, Biomacromolecules 17 (9) (2016)
3076–3084, https://doi.org/10.1021/acs.biomac.6b00995.
[106] H.P. Zhang, X.Y. Wang, S.J. Min, M. Mandal, M.Y. Yang, L.J. Zhu,
Hydroxyapatite/sericin composite film prepared through mineralization of
flexible ethanol-treated sericin film with simulated body fluids, Ceram. Int. 40 (1)
(2014) 985–991, https://doi.org/10.1016/j.ceramint.2013.06.095.
[107] R. Wang, J. Li, W. Chen, T. Xu, S. Yun, Z. Xu, Z. Xu, T. Sato, B. Chi, H. Xu,
A biomimetic mussel-inspired ε-Poly-l-lysine hydrogel with robust tissue-anchor
and anti-infection capacity, Adv. Funct. Mater. 27 (8) (2017), 1604894, https://
doi.org/10.1002/adfm.201604894.
[108] Y. Wang, R. Cai, G. Tao, P. Wang, H. Zuo, P. Zhao, A. Umar, H. He, A novel
AgNPs/sericin/agar film with enhanced mechanical property and antibacterial
capability, Molecules 23 (7) (2018) 1821, https://doi.org/10.3390/
molecules23071821.
[109] R. Cai, T. Gang, H. He, K. Song, H. Zuo, W. Jiang, Y.J.M. Wang, One-step synthesis
of silver nanoparticles on polydopamine-coated sericin/polyvinyl alcohol
composite films for potential antimicrobial applications, Molecules 22 (5) (2017)
721, https://doi.org/10.3390/molecules22050721.
[110] L. Liu, R. Cai, Y. Wang, G. Tao, L. Ai, P. Wang, M. Yang, H. Zuo, P. Zhao, H. He,
Polydopamine-assisted silver nanoparticle self-assembly on sericin/agar film for
potential wound dressing application, Int. J. Mol. Sci. 19 (10) (2018) 2875,
https://doi.org/10.3390/ijms19102875.
[111] W. Li, Z. Huang, R. Cai, W. Yang, H. He, Y. Wang, Rational design of Ag/ZnO
hybrid nanoparticles on sericin/agarose composite film for enhanced
antimicrobial applications, Int. J. Mol. Sci. 22 (1) (2020) 105, https://doi.org/
10.3390/ijms22010105.
[112] P. Aramwit, S. Palapinyo, T. Srichana, S. Chottanapund, P. Muangman, Silk
sericin ameliorates wound healing and its clinical efficacy in burn wounds, Arch.
Dermatol. Res. 305 (7) (2013) 585–594, https://doi.org/10.1007/s00403-013-
1371-4.
[113] P. Aramwit, O. Keongamaroon, T. Siritientong, N. Bang, O. Supasyndh, Sericin
cream reduces pruritus in hemodialysis patients: a randomized, double-blind,
placebo-controlled experimental study, BMC Nephrol. 13 (2012) 119, https://doi.
org/10.1186/1471-2369-13-119.
[114] J.W. Kim, Y.Y. Jo, J.Y. Kim, J.h. Oh, B.E. Yang, S.G. Kim, Clinical study for silk
mat application into extraction socket: a split-mouth, randomized clinical trial,
Appl. Sci. 9 (6) (2019), https://doi.org/10.3390/app9061208.
[115] Y. Song, C. Zhang, J. Zhang, N. Sun, K. Huang, H. Li, Z. Wang, K. Huang, L. Wang,
An injectable silk sericin hydrogel promotes cardiac functional recovery after
ischemic myocardial infarction, Acta Biomater. 41 (2016) 210–223, https://doi.
org/10.1016/j.actbio.2016.05.039.
[116] M. Yang, Y. Wang, T. Gang, R. Cai, W. Peng, L. Liu, L. Ai, H. Zuo, P. Zhao, U.J.
N. Ahmad, Fabrication of sericin/agrose gel loaded lysozyme and its potential in
wound dressing application, Nanomaterials 8 (4) (2018) 235, https://doi.org/
10.3390/nano8040235.
[117] S. Sapru, A.K. Ghosh, S.C. Kundu, Non-immunogenic, porous and antibacterial
chitosan and Antheraea mylitta silk sericin hydrogels as potential dermal
substitute, Carbohydr. Polym. 167 (2017) 196–209, https://doi.org/10.1016/j.
carbpol.2017.02.098.
[118] Y. Zhang, J. Liu, L. Huang, Z. Wang, L. Wang, Design and performance of a
sericin-alginate interpenetrating network hydrogel for cell and drug delivery, Sci.
Rep. 5 (2015), 12374, https://doi.org/10.1038/srep12374.
17
Biomaterials 287 (2022) 121638
[119] B. Kundu, S.C. Kundu, Silk sericin/polyacrylamide in situ forming hydrogels for
dermal reconstruction, Biomaterials 33 (30) (2012) 7456–7467, https://doi.org/
10.1016/j.biomaterials.2012.06.091.
[120] L. Shi, N. Yang, H. Zhang, L. Chen, L. Tao, Y. Wei, H. Liu, Y. Luo, A novel poly
(gamma-glutamic acid)/silk-sericin hydrogel for wound dressing: synthesis,
characterization and biological evaluation, Mater. Sci. Eng., C 48 (2015)
533–540, https://doi.org/10.1016/j.msec.2014.12.047.
[121] R. Xue, Y. Liu, Q. Zhang, C. Liang, H. Qin, P. Liu, K. Wang, X. Zhang, L. Chen,
Y. Wei, Shape changes and interaction mechanism of Escherichia coli cells treated
with sericin and use of a sericin-based hydrogel for wound healing, Appl. Environ.
Microbiol. 82 (15) (2016) 4663–4672, https://doi.org/10.1128/AEM.00643-16.
[122] C. Yang, R. Xue, Q. Zhang, S. Yang, P. Liu, L. Chen, K. Wang, X. Zhang, Y. Wei,
Nanoclay cross-linked semi-IPN silk sericin/poly(NIPAm/LMSH) nanocomposite
hydrogel: an outstanding antibacterial wound dressing, Mater. Sci. Eng., C 81
(2017) 303–313, https://doi.org/10.1016/j.msec.2017.08.008.
[123] C. Qi, Y. Deng, L. Xu, C. Yang, Y. Zhu, G. Wang, Z. Wang, L. Wang, A sericin/
graphene oxide composite scaffold as a biomimetic extracellular matrix for
structural and functional repair of calvarial bone, Theranostics 10 (2) (2020)
741–756, https://doi.org/10.7150/thno.39502.
[124] T. Siritienthong, J. Ratanavaraporn, P. Aramwit, Development of ethyl alcohol-
precipitated silk sericin/polyvinyl alcohol scaffolds for accelerated healing of full-
thickness wounds, Int. J. Pharm. 439 (1–2) (2012) 175–186, https://doi.org/
10.1016/j.ijpharm.2012.09.043.
[125] S. Dinescu, B. Galateanu, M. Albu, A. Lungu, E. Radu, A. Hermenean,
M. Costache, Biocompatibility assessment of novel collagen-sericin scaffolds
improved with hyaluronic Acid and chondroitin sulfate for cartilage regeneration,
BioMed Res. Int. 2013 (2013), 598056, https://doi.org/10.1155/2013/598056.
[126] S. Nayak, S.C. Kundu, Sericin-carboxymethyl cellulose porous matrices as cellular
wound dressing material, J. Biomed. Mater. Res. 102 (6) (2014) 1928–1940,
https://doi.org/10.1002/jbm.a.34865.
[127] M. Yang, Y. Shuai, C. Zhang, Y. Chen, L. Zhu, C. Mao, H. OuYang, Biomimetic
nucleation of hydroxyapatite crystals mediated by Antheraea pernyi silk sericin
promotes osteogenic differentiation of human bone marrow derived
mesenchymal stem cells, Biomacromolecules 15 (4) (2014) 1185–1193, https://
doi.org/10.1021/bm401740x.
[128] Z. Jiayao, Z. Guanshan, Z. Jinchi, C. Yuyin, Z. Yongqiang, Antheraea pernyi silk
sericin mediating biomimetic nucleation and growth of hydroxylapatite crystals
promoting bone matrix formation, Microsc. Res. Tech. 80 (3) (2017) 305–311,
https://doi.org/10.1002/jemt.22793.
[129] P. Aramwit, J. Ratanavaraporn, S. T, Improvement of physical and wound
adhesion properties of silk sericin and polyvinyl alcohol dressing using glycerin,
Adv. Skin Wound Care 28 (8) (2015) 10, https://doi.org/10.1097/01.
ASW.0000467304.77196.b9.
[130] J. Wang, X. Li, Y. Song, Q. Su, X. Xiaohalati, W. Yang, L. Xu, B. Cai, G. Wang,
Z. Wang, L. Wang, Injectable silk sericin scaffolds with programmable shape-
memory property and neuro-differentiation-promoting activity for individualized
brain repair of severe ischemic stroke, Bioact. Mater. 6 (7) (2021) 1988–1999,
https://doi.org/10.1016/j.bioactmat.2020.12.017.
[131] T. Siritientong, A. Angspatt, J. Ratanavaraporn, P. Aramwit, Clinical potential of a
silk sericin-releasing bioactive wound dressing for the treatment of split-thickness
skin graft donor sites, Pharm. Res. (N. Y.) 31 (1) (2014) 104–116, https://doi.org/
10.1007/s11095-013-1136-y.
[132] S. Napavichayanun, R. Yamdech, P. Aramwit, The safety and efficacy of bacterial
nanocellulose wound dressing incorporating sericin and polyhexamethylene
biguanide: in vitro, in vivo and clinical studies, Arch. Dermatol. Res. 308 (2)
(2016) 123–132, https://doi.org/10.1007/s00403-016-1621-3.
[133] Clinical trials. http://clinicaltrials.gov/ct2/results?term=sericin, 2022. (Accessed
3 May 2022).
[134] B.J. Parker, D.I. Rhodes, C.M. O’Brien, A.E. Rodda, N.R. Cameron, Nerve
guidance conduit development for primary treatment of peripheral nerve
transection injuries: a commercial perspective, Acta Biomater. 135 (3) (2021)
64–86, https://doi.org/10.1016/j.actbio.2021.08.052.
[135] M. Lin, Z. Zheng, L. Yang, M. Luo, L. Fu, B. Lin, C. Xu, A high-performance,
sensitive, wearable multifunctional sensor based on rubber/CNT for human
motion and skin temperature detection, Adv. Mater. 34 (1) (2022), e2107309,
https://doi.org/10.1002/adma.202107309.
[136] X. Liang, H. Li, J. Dou, Q. Wang, W. He, C. Wang, D. Li, J.M. Lin, Y. Zhang, Stable
and biocompatible carbon nanotube ink mediated by silk protein for printed
electronics, Adv. Mater. 32 (31) (2020), e2000165, https://doi.org/10.1002/
adma.202000165.
[137] H. Ma, J. Li, J. Zhou, Q. Luo, W. Wu, Z. Mao, W. Ma, Screen-printed carbon black/
recycled Sericin@Fabrics for wearable sensors to monitor sweat loss, ACS Appl.
Mater. Interfaces 14 (9) (2022) 11813–11819, https://doi.org/10.1021/
acsami.1c23341.
[138] Y. An, C. Luo, D. Yao, S. Wen, P. Zheng, S. Chi, Y. Yang, J. Chang, Y. Deng,
C. Wang, Natural cocoons enabling flexible and stable fabric lithium-sulfur full
batteries, Nano-Micro Lett. 13 (1) (2021) 84, https://doi.org/10.1007/s40820-
021-00609-3.
[139] Q. Duan, Y. Lu, Silk sericin as a green adhesive to fabricate a textile strain sensor
with excellent electromagnetic shielding performance, ACS Appl. Mater.
Interfaces 13 (24) (2021) 28832–28842, https://doi.org/10.1021/
acsami.1c05671.
[140] H. Wang, F. Meng, Y. Cai, L. Zheng, Y. Li, Y. Liu, Y. Jiang, X. Wang, X. Chen,
Sericin for resistance switching device with multilevel nonvolatile memory, Adv.
Mater. 25 (38) (2013) 5498–5503, https://doi.org/10.1002/adma.201301983.
J. Liu et al.
[141] H.P. Felgueiras, M.T.P. Amorim, Functionalization of electrospun polymeric
wound dressings with antimicrobial peptides, Colloids Surf., B 156 (2017)
133–148, https://doi.org/10.1016/j.colsurfb.2017.05.001.
[142] D. Chouhan, N. Dey, N. Bhardwaj, B.B. Mandal, Emerging and innovative
approaches for wound healing and skin regeneration: current status and
advances, Biomaterials 216 (2019), 119267, https://doi.org/10.1016/j.
biomaterials.2019.119267.
[143] Y.J. Son, J.W. Tse, Y. Zhou, W. Mao, E.K.F. Yim, H.S. Yoo, Biomaterials and
controlled release strategy for epithelial wound healing, Biomater. Sci. 7 (11)
(2019) 4444–4471, https://doi.org/10.1039/c9bm00456d.
[144] R. Wang, J. Li, W. Chen, T. Xu, S. Yun, Z. Xu, Z. Xu, T. Sato, B. Chi, H. Xu,
A biomimetic mussel-inspired ε-Poly-l-lysine hydrogel with robust tissue-anchor
and anti-infection capacity, Adv. Funct. Mater. 27 (8) (2017), https://doi.org/
10.1002/adfm.201604894.
[145] R. Cai, G. Tao, H. He, K. Song, H. Zuo, W. Jiang, Y. Wang, One-step synthesis of
silver nanoparticles on polydopamine-coated sericin/polyvinyl alcohol composite
films for potential antimicrobial applications, Molecules 22 (5) (2017), https://
doi.org/10.3390/molecules22050721.
[146] L. Liu, R. Cai, Y. Wang, G. Tao, L. Ai, P. Wang, M. Yang, H. Zuo, P. Zhao, H. He,
Polydopamine-assisted silver nanoparticle self-assembly on sericin/agar film for
potential wound dressing application, Int. J. Mol. Sci. 19 (10) (2018), https://doi.
org/10.3390/ijms19102875.
[147] T.E. Brown, K.S. Anseth, Spatiotemporal hydrogel biomaterials for regenerative
medicine, Chem. Soc. Rev. 46 (21) (2017) 6532–6552, https://doi.org/10.1039/
c7cs00445a.
[148] S. Jasmine, B.B. Mandal, Types and properties of non-mulberry silk biomaterials
for tissue engineering applications, Silk Biomater. Tissue Eng. Regen. Med. (2014)
275–298, https://doi.org/10.1533/9780857097064.2.275.
[149] J.J. Zhao, D.C. Liu, Y.H. Yu, H. Tang, Development of gelatin-silk sericin
incorporated with poly(vinyl alcohol) hydrogel-based nanocomposite for
articular cartilage defects in rat knee Joint repair, J. Biomed. Nanotechnol. 17
(2021) 242–252, https://doi.org/10.1166/jbn.2021.3024.
[150] M. Yang, Y. Wang, G. Tao, R. Cai, P. Wang, L. Liu, L. Ai, H. Zuo, P. Zhao, A. Umar,
C. Mao, H. He, Fabrication of sericin/agrose gel loaded lysozyme and its potential
in wound dressing application, Nanomaterials 8 (4) (2018), https://doi.org/
10.3390/nano8040235.
[151] G. Tao, R. Cai, Y. Wang, H. Zuo, H. He, Fabrication of antibacterial sericin based
hydrogel as an injectable and mouldable wound dressing, Mater. Sci. Eng., C 119
(2021), 111597, https://doi.org/10.1016/j.msec.2020.111597.
[152] M. Zhang, D. Wang, N. Ji, S. Lee, G. Wang, Y. Zheng, X. Zhang, L. Yang, Z. Qin,
Y. Yang, Bioinspired design of sericin/chitosan/Ag@MOF/GO hydrogels for
efficiently combating resistant bacteria, rapid hemostasis, and wound healing,
Polymers (Basel) 13 (16) (2021) 2812, https://doi.org/10.3390/polym13162812.
[153] Y. Zhang, R. Jiang, A. Fang, Y. Zhao, T. Wu, X. Cao, P. Liang, D. Xia, G. Zhang,
A highly transparent, elastic, injectable sericin hydrogel induced by ultrasound,
Polym. Test. 77 (2019), 105890, https://doi.org/10.1016/j.
polymertesting.2019.05.006.
[154] Y. Zhu, H. Liu, S. Qin, C. Yang, Q. Lv, Z. Wang, L. Wang, Antibacterial sericin
cryogels promote hemostasis by facilitating the activation of coagulation pathway
and platelets, Adv. Healthc. Mater. (2022), e2102717, https://doi.org/10.1002/
adhm.202102717.
[155] S. Abdulghani, G.R. Mitchell, Biomaterials for in situ tissue regeneration: a
review, Biomolecules 9 (11) (2019) 750, https://doi.org/10.3390/biom9110750.
[156] W.H. De Jong, P.J. Borm, Drug delivery and nanoparticles:applications and
hazards, Int. J. Nanomed. 3 (2) (2008) 133–149, https://doi.org/10.2147/ijn.
s596.
[157] M.J. Mitchell, M.M. Billingsley, R.M. Haley, M.E. Wechsler, N.A. Peppas,
R. Langer, Engineering precision nanoparticles for drug delivery, Nat. Rev. Drug
Discov. 20 (2) (2021) 101–124, https://doi.org/10.1038/s41573-020-0090-8.
[158] A.A. Saei, M. Yazdani, S.E. Lohse, Z. Bakhtiary, V. Serpooshan, M. Ghavami,
M. Asadian, S. Mashaghi, E.C. Dreaden, A. Mashaghi, M. Mahmoudi, Nanoparticle
surface functionality dictates cellular and systemic toxicity, Chem. Mater. 29 (16)
(2017) 6578–6595, https://doi.org/10.1021/acs.chemmater.7b01979.
[159] J. Lazarovits, Y.Y. Chen, E.A. Sykes, W.C. Chan, Nanoparticle-blood interactions:
the implications on solid tumour targeting, Chem. Commun. 51 (14) (2015)
2756–2767, https://doi.org/10.1039/c4cc07644c.
[160] T. Limongi, M. Canta, L. Racca, A. Ancona, S. Tritta, V. Vighetto, V. Cauda,
Improving dispersal of therapeutic nanoparticles in the human body,
Nanomedicine 14 (7) (2019) 797–801, https://doi.org/10.2217/nnm-2019-0070.
[161] D. Zhang, J. Qiu, L. Shi, Y. Liu, B. Pan, B. Xing, The mechanisms and
environmental implications of engineered nanoparticles dispersion, Sci. Total
Environ. 722 (2020), 137781, https://doi.org/10.1016/j.scitotenv.2020.137781.
[162] M. Jahanshahi, E. Kowsari, V. Haddadi-Asl, M. Khoobi, J.H. Lee, F.B. Kadumudi,
S. Talebian, N. Kamaly, M. Mehrali, Sericin grafted multifunctional curcumin
loaded fluorinated graphene oxide nanomedicines with charge switching
properties for effective cancer cell targeting, Int. J. Pharm. 572 (2019), 118791,
https://doi.org/10.1016/j.ijpharm.2019.118791.
[163] D. Hu, T. Li, Z. Xu, D. Liu, M. Yang, L. Zhu, Self-stabilized silk sericin-based
nanoparticles: in vivo biocompatibility and reduced doxorubicin-induced toxicity,
Acta Biomater. 74 (2018) 385–396, https://doi.org/10.1016/j.
actbio.2018.05.024.
[164] X. Li, S. Hou, J. Chen, C.E. He, Y.E. Gao, Y. Lu, D. Jia, X. Ma, P. Xue, Y. Kang,
Z. Xu, Engineering silk sericin decorated zeolitic imidazolate framework-8
nanoplatform to enhance chemotherapy, Colloids Surf., B 200 (2021), 111594,
https://doi.org/10.1016/j.colsurfb.2021.111594.
18
Biomaterials 287 (2022) 121638
[165] J. Liu, Q.L. Li, J.X. Zhang, L. Huang, C. Qi, L.M. Xu, X.X. Liu, G.B. Wang, L. Wang,
Z. Wang, Safe and effective reversal of cancer multidrug resistance using sericin-
coated mesoporous silica nanoparticles for lysosome-targeting delivery in mice,
Small 13 (9) (2017), 1602567, https://doi.org/10.1002/smll.201602567.
[166] J. Kanoujia, M. Singh, P. Singh, S.A. Saraf, Novel genipin crosslinked atorvastatin
loaded sericin nanoparticles for their enhanced antihyperlipidemic activity,
Mater. Sci. Eng., C 69 (2016) 967–976, https://doi.org/10.1016/j.
msec.2016.08.011.
[167] K. Suktham, T. Koobkokkruad, T. Wutikhun, S. Surassmo, Efficiency of
resveratrol-loaded sericin nanoparticles: promising bionanocarriers for drug
delivery, Int. J. Pharm. 537 (1–2) (2018) 48–56, https://doi.org/10.1016/j.
ijpharm.2017.12.015.
[168] O.I. Parisi, M. Fiorillo, L. Scrivano, M.S. Sinicropi, V. Dolce, D. Iacopetta, F. Puoci,
A.R. Cappello, Sericin/Poly(ethylcyanoacrylate) nanospheres by interfacial
polymerization for enhanced bioefficacy of fenofibrate: in vitro and in vivo
studies, Biomacromolecules 16 (10) (2015) 3126–3133, https://doi.org/
10.1021/acs.biomac.5b00746.
[169] W. Guo, L. Deng, J. Yu, Z. Chen, Y. Woo, H. Liu, T. Li, T. Lin, H. Chen, M. Zhao,
L. Zhang, G. Li, Y. Hu, Sericin nanomicelles with enhanced cellular uptake and
pH-triggered release of doxorubicin reverse cancer drug resistance, Drug Deliv. 25
(1) (2018) 1103–1116, https://doi.org/10.1080/10717544.2018.1469686.
[170] W. Guo, L. Deng, Z. Chen, Z. Chen, J. Yu, H. Liu, T. Li, T. Lin, H. Chen, M. Zhao,
L. Zhang, G. Li, Y. Hu, Vitamin B12-conjugated sericin micelles for targeting
CD320-overexpressed gastric cancer and reversing drug resistance, Nanomedicine
14 (3) (2019) 353–370, https://doi.org/10.2217/nnm-2018-0321.
[171] K. Boonpavanitchakul, L.K. Bast, N. Bruns, R. Magaraphan, Silk sericin-
polylactide protein-polymer conjugates as biodegradable amphiphilic materials
and their application in drug release systems, Bioconjugate Chem. 31 (10) (2020)
2312–2324, https://doi.org/10.1021/acs.bioconjchem.0c00399.
[172] L. Huang, K. Tao, J. Liu, C. Qi, L. Xu, P. Chang, J. Gao, X. Shuai, G. Wang,
Z. Wang, L. Wang, Design and fabrication of multifunctional sericin nanoparticles
for tumor targeting and pH-responsive subcellular delivery of cancer
chemotherapy drugs, ACS Appl. Mater. Interfaces 8 (10) (2016) 6577–6585,
https://doi.org/10.1021/acsami.5b11617.
[173] H. He, G. Tao, Y. Wang, R. Cai, P. Guo, L. Chen, H. Zuo, P. Zhao, Q. Xia, In situ
green synthesis and characterization of sericin-silver nanoparticle composite with
effective antibacterial activity and good biocompatibility, Mater. Sci. Eng., C 80
(2017) 509–516, https://doi.org/10.1016/j.msec.2017.06.015.
[174] J. Wang, S. Yang, C. Li, Y. Miao, L. Zhu, C. Mao, M. Yang, Nucleation and
assembly of silica into protein-based nanocomposites as effective anticancer drug
carriers using self-assembled silk protein nanostructures as biotemplates, ACS
Appl. Mater. Interfaces 9 (27) (2017) 22259–22267, https://doi.org/10.1021/
acsami.7b05664.
[175] W. Chaisabai, A. Khamhaengpol, S. Siri, Sericins of mulberry and non-mulberry
silkworms for eco-friendly synthesis of silver nanoparticles, Artif. Cell Nanomed.
Biotechnol. 46 (3) (2018) 536–543, https://doi.org/10.1080/
21691401.2017.1328686.
[176] D. Tian, H. Xu, B. Xiao, X. Zhou, X. Liu, Z. Zhou, H.K. Patra, N. Slater, J. Tang,
Y. Shen, Single-step formulation of levodopa-based nanotheranostics - strategy for
ultra-sensitive high longitudinal relaxivity MRI guided switchable therapeutics,
Biomater. Sci. 8 (6) (2020) 1615–1621, https://doi.org/10.1039/c9bm01799b.
[177] O. Akturk, Z. Gun Gok, O. Erdemli, M. Yigitoglu, One-pot facile synthesis of silk
sericin-capped gold nanoparticles by UVC radiation: investigation of stability,
biocompatibility, and antibacterial activity, J. Biomed. Mater. Res. 107 (12)
(2019) 2667–2679, https://doi.org/10.1002/jbm.a.36771.
[178] L. Deng, W. Guo, G. Li, Y. Hu, L.M. Zhang, Hydrophobic IR780 loaded sericin
nanomicelles for phototherapy with enhanced antitumor efficiency, Int. J. Pharm.
566 (2019) 549–556, https://doi.org/10.1016/j.ijpharm.2019.05.075.
[179] M. Arjama, S. Mehnath, M. Rajan, M. Jeyaraj, Sericin/RBA embedded gellan gum
based smart nanosystem for pH responsive drug delivery, Int. J. Biol. Macromol.
120 (Pt B) (2018) 1561–1571, https://doi.org/10.1016/j.ijbiomac.2018.09.146.
[180] S. Mehnath, M.A. Ayisha Sithika, M. Arjama, M. Rajan, R. Amarnath Praphakar,
M. Jeyaraj, Sericin-chitosan doped maleate gellan gum nanocomposites for
effective cell damage in Mycobacterium tuberculosis, Int. J. Biol. Macromol. 122
(2019) 174–184, https://doi.org/10.1016/j.ijbiomac.2018.10.167.
[181] E. Hadipour-Goudarzi, M. Montazer, M. Latifi, A.A. Aghaji, Electrospinning of
chitosan/sericin/PVA nanofibers incorporated with in situ synthesis of nano
silver, Carbohydr. Polym. 113 (2014) 231–239, https://doi.org/10.1016/j.
carbpol.2014.06.082.
[182] S. Doakhan, M. Montazer, A. Rashidi, R. Moniri, M.B. Moghadam, Influence of
sericin/TiO(2) nanocomposite on cotton fabric: part 1. Enhanced antibacterial
effect, Carbohydr. Polym. 94 (2) (2013) 737–748, https://doi.org/10.1016/j.
carbpol.2013.01.023.
[183] T. Khampieng, P. Aramwit, P. Supaphol, Silk sericin loaded alginate
nanoparticles: preparation and anti-inflammatory efficacy, Int. J. Biol. Macromol.
80 (2015) 636–643, https://doi.org/10.1016/j.ijbiomac.2015.07.018.
[184] N. Nagai, Y. Iwai, S. Deguchi, H. Otake, K. Kanai, N. Okamoto, Y. Shimomura,
Therapeutic potential of a combination of magnesium hydroxide nanoparticles
and sericin for epithelial corneal wound healing, Nanomaterials 9 (5) (2019) 768,
https://doi.org/10.3390/nano9050768.
[185] T. Chlapanidas, S. Perteghella, F. Leoni, S. Farago, M. Marazzi, D. Rossi,
E. Martino, R. Gaggeri, S. Collina, TNF-alpha blocker effect of naringenin-loaded
sericin microparticles that are potentially useful in the treatment of psoriasis, Int.
J. Mol. Sci. 15 (8) (2014) 13624–13636, https://doi.org/10.3390/
ijms150813624.
J. Liu et al.
[186] Z. Liu, Y. Cai, Y. Jia, L. Liu, X. Kong, S.C. Kundu, J. Yao, One-step synthesis of
natural silk sericin-based microcapsules with bionic structures, Macromol. Rapid
Commun. 35 (19) (2014) 1668–1672, https://doi.org/10.1002/marc.201400304.
[187] E. Bari, C.R. Arciola, B. Vigani, B. Crivelli, P. Moro, G. Marrubini, M. Sorrenti,
L. Catenacci, G. Bruni, T. Chlapanidas, E. Lucarelli, S. Perteghella, M.L. Torre, In
vitro effectiveness of microspheres based on silk sericin and chlorella vulgaris or
arthrospira platensis for wound healing applications, Materials 10 (9) (2017) 983,
https://doi.org/10.3390/ma10090983.
[188] W. Li, X. Su, Q. Zhong, Z. Liu, Y. Cai, J. Yao, Influence of reaction conditions on
the self-assembly of the natural silk sericin protein, Microsc. Res. Tech. 80 (3)
(2017) 298–304, https://doi.org/10.1002/jemt.22666.
[189] J. Liu, Y. Deng, D. Fu, Y. Yuan, Q. Li, L. Shi, G. Wang, Z. Wang, L. Wang, Sericin
microparticles enveloped with metal-organic networks as a pulmonary targeting
delivery system for intra-tracheally treating metastatic lung cancer, Bioact. Mater.
6 (1) (2021) 273–284, https://doi.org/10.1016/j.bioactmat.2020.08.006.
19
Biomaterials 287 (2022) 121638
[190] N.E. Kurland, T. Dey, C. Wang, S.C. Kundu, V.K. Yadavalli, Silk protein
lithography as a route to fabricate sericin microarchitectures, Adv. Mater. 26 (26)
(2014) 4431–4437, https://doi.org/10.1002/adma.201400777.
[191] S. Nayak, S. Dey, S.C. Kundu, Silk sericin-alginate-chitosan microcapsules:
hepatocytes encapsulation for enhanced cellular functions, Int. J. Biol. Macromol.
65 (2014) 258–266, https://doi.org/10.1016/j.ijbiomac.2014.01.042.
[192] C.S. Chen, F. Zeng, X. Xiao, Z. Wang, X.L. Li, R.W. Tan, W.Q. Liu, Y.S. Zhang, Z.
D. She, S.J. Li, Three-dimensionally printed silk-sericin-based hydrogel scaffold: a
promising visualized dressing material for real-time monitoring of wounds, ACS
Appl. Mater. Interfaces 10 (40) (2018) 33879–33890, https://doi.org/10.1021/
acsami.8b10072.
[193] Y. Deng, C. Yang, Y. Zhu, W. Liu, H. Li, L. Wang, W. Chen, Z. Wang, L. Wang,
Lamprey-teeth-inspired oriented antibacterial sericin microneedles for infected
wound healing improvement, Nano Lett. 22 (7) (2022) 2702–2711, https://doi.
org/10.1021/acs.nanolett.1c04573.