Sericin Protein: Structure, Properties, and Applications

Abstract

Silk sericin, the glue protein binding fibroin fibers together, is present in the Bombyx mori silkworms’ cocoons. In recent years, sericin has gained attention for its wide range of properties and possible opportunities for various applications, as evidenced by the meta-analysis conducted in this review. Sericin extraction methods have evolved over the years to become more efficient and environmentally friendly, preserving its structure. Due to its biocompatibility, biodegradability, anti-inflammatory, antibacterial, antioxidant, UV-protective, anti-tyrosinase, anti-aging, and anti-cancer properties, sericin is increasingly used in biomedical fields like drug delivery, tissue engineering, and serum-free cell culture media. Beyond healthcare, sericin shows promise in industries such as textiles, cosmetics, and food packaging. This review aims to highlight recent advancements in sericin extraction, research, and applications, while also summarizing key findings from earlier studies.

Full text

Citation: Aad, R.; Dragojlov, I.;
Vesentini, S. Sericin Protein: Structure,
Properties, and Applications. J. Funct.
Biomater. 2024,15, 322. https://
doi.org/10.3390/jfb15110322
Academic Editor: Matt Kipper
Received: 30 September 2024
Revised: 24 October 2024
Accepted: 26 October 2024
Published: 29 October 2024
Copyright: © 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Journal of
Functional
Biomaterials
Review
Sericin Protein: Structure, Properties, and Applications
Rony Aad , Ivana Dragojlov and Simone Vesentini *
Department of Electronics, Information, and Bioengineering, Politecnico di Milano, 20133 Milan, Italy;
rony.aad@polimi.it (R.A.); ivana.dragojlov@polimi.it (I.D.)
*Correspondence: simone.vesentini@polimi.it
Abstract: Silk sericin, the glue protein binding fibroin fibers together, is present in the Bombyx mori
silkworms’ cocoons. In recent years, sericin has gained attention for its wide range of properties
and possible opportunities for various applications, as evidenced by the meta-analysis conducted in
this review. Sericin extraction methods have evolved over the years to become more efficient and
environmentally friendly, preserving its structure. Due to its biocompatibility, biodegradability, anti-
inflammatory, antibacterial, antioxidant, UV-protective, anti-tyrosinase, anti-aging, and anti-cancer
properties, sericin is increasingly used in biomedical fields like drug delivery, tissue engineering,
and serum-free cell culture media. Beyond healthcare, sericin shows promise in industries such as
textiles, cosmetics, and food packaging. This review aims to highlight recent advancements in sericin
extraction, research, and applications, while also summarizing key findings from earlier studies.
Keywords: sericin; silk; biobased materials; extraction processes; silkworm Bombyx mori
1. Introduction
Silk produced by Bombyx mori silkworms is composed of two main proteins, namely
fibroin and sericin. Silk fibroin (70–75% of the silk proteins) is a fibrous protein secreted
by the silkworm in two strands coming from the right and left sides of the excretory
duct. The two strands are held together by the sericin (25–30% of the silk proteins), a
globular protein being secreted at the same time and acting as the “gum” coating the
fibroin strands and allowing them to stick to each other, forming the final silk thread. After
being secreted, sericin loses its rubbery texture and acts as a rigid adhesive, binding the
cocoon fibers as it forms. After 3–4 days, the weaving period stops, and the final cocoon
is a rigid shell that preserves the chrysalis until its transformation into butterfly. Reelers
and silk processors prioritize fibroin within the fiber exclusively, and traditionally, sericin,
viewed as a secondary product, is discarded along with degumming water. Furthermore,
unlike fibroin, which has enjoyed extensive use in non-textile sectors, particularly in
biomedical applications, sericin was once considered cytotoxic and inappropriate for
medical purposes [
1
]. Just as an example of this initial consideration, an extract from a
highly cited article published in 2003 is reported. In the section regarding the utility of
silk-based proteins in biomedical applications, it is stated “
. . .
it is clear that the sericin
glue-like proteins are the major cause of adverse problems with biocompatibility and
hypersensitivity to silk
. . .
if sericin is removed, the biological responses to the core fibroin
fibers appear to be comparable to most other commonly used biomaterials
. . .
” [
1
]. This
is just one example, but throughout the same article, there are many similar statements.
Even though the same principal investigator published another paper in 2007 refuting
the adverse effects of sericin, the original idea persisted, and the scientific community
remained convinced that sericin should be removed and disregarded [
1
]. Nonetheless,
recent breakthroughs in understanding sericin’s structure, properties, biocompatibility,
and processability have highlighted its distinctiveness and the potential for its widespread
adoption across various industries such as cosmetics, medical, food, fiber, and beyond [
2
].
Starting from the meta-analysis of the two main proteins with a particular focus on sericin,
J. Funct. Biomater. 2024,15, 322. https://doi.org/10.3390/jfb15110322 https://www.mdpi.com/journal/jfb

J. Funct. Biomater. 2024,15, 322 2 of 36
the attention will move on to the main molecular features that are responsible for the
behavior of sericin. A detailed description of possible methods to extract sericin is also
given with attention to methods that prevent protein degradation. Finally, consolidated
applications and possible future directions and markets for the sericin are presented.
2. Meta-Analysis
2.1. Sericin-Based Studies
Various studies have been published from 1926 until 2024 on sericin, concerning
various extraction methods of sericin, its inherent characteristics, and its vast range of appli-
cations. The literature abounds with comprehensive examinations of sericin’s multifaceted
properties. In this dedicated section, a comprehensive meta-analysis study was systemati-
cally conducted scrutinizing sericin-related content across three prominent online databases:
PubMed https://pubmed.ncbi.nlm.nih.gov/?term=sericin&sort=pubdate, (accessed on
10 June 2024), Science Direct https://www.sciencedirect.com/search?qs=sericin (accessed
on 10 June 2024)), and SpringerLink (https://link.springer.com/search?query=sericin (ac-
cessed on 10 June 2024). As detailed in Table 1below, the collective body of work surpasses
11,000 studies, predominantly comprised of research articles.
Table 1. Types and numbers of published studies on sericin in online libraries.
Libraries PubMed Science Direct SpringerLink
Articles 1057 Research articles 2759 Articles 1647
Full Texts 1001 Book chapters 785 Research articles 1279
Associated Data 288 Encyclopedia 67 Chapters 927
Reviews 79 Review articles 837 Reference work entry 138
Systematic Reviews 3 Conference
abstracts 38 Conference papers 69
Randomized
controlled trials 7 - - Protocol 16
Clinical Trials 9 - - - -
Meta-analysis 1 - - - -
The presented results stem from a comprehensive search across three prominent
databases: PubMed, ScienceDirect, and SpringerLink. The graphical representation of the
data is illustrated in Figure 1. Over the past decade, there has been a steady increase in
the volume of sericin-related publications, with notable peaks in research output during
specific years, possibly driven by advances in biotechnology and material science. Research
articles constitute the predominant type of publication across all three databases, suggest-
ing a high level of experimental engagement with sericin. This is followed by full texts
and associated data in PubMed, review articles and book chapters in ScienceDirect, and
chapters and books in SpringerLink. Notably, the prevalence of research articles highlights
the continuous expansion of empirical studies, while the presence of review articles, book
chapters, and monographs indicates a growing interest in consolidating and synthesizing
knowledge about silk sericin. PubMed, with its focus on biomedical research, shows a
stronger representation of studies on sericin’s medical applications, while ScienceDirect
and SpringerLink cover a broader spectrum of industrial uses, including food packaging,
textiles, and cosmetics. Furthermore, preliminary citation analysis suggests that research
articles focusing on biomedical applications, particularly in drug delivery and tissue engi-
neering, are among the most frequently cited in the literature, indicating their significant
scientific impact and practical relevance. This analysis not only underscores robust en-
gagement with sericin-related studies but also reveals the multidisciplinary nature of this
research. However, gaps remain, particularly in exploring the full industrial potential of
sericin in non-medical sectors, signaling opportunities for future investigation.

J. Funct. Biomater. 2024,15, 322 3 of 36
J. Funct. Biomater. 2024, 15, x FOR PEER REVIEW 3 of 38
synthesizing knowledge about silk sericin. PubMed, with its focus on biomedical research,
shows a stronger representation of studies on sericin’s medical applications, while Sci-
enceDirect and SpringerLink cover a broader spectrum of industrial uses, including food
packaging, textiles, and cosmetics. Furthermore, preliminary citation analysis suggests
that research articles focusing on biomedical applications, particularly in drug delivery
and tissue engineering, are among the most frequently cited in the literature, indicating
their significant scientific impact and practical relevance. This analysis not only under-
scores robust engagement with sericin-related studies but also reveals the multidiscipli-
nary nature of this research. However, gaps remain, particularly in exploring the full in-
dustrial potential of sericin in non-medical sectors, signaling opportunities for future in-
vestigation.
(a)
(b)
Figure 1. (a) Number of publication types on sericin in the three databases. (b) Comparison of the
number of publications in the three databases each year.
2.2. Fibroin-Based Studies
The findings presented in this meta-analysis are based on an extensive review of the
literature concerning fibroin. An analysis of data from prominent databases such as Pub-
Med, ScienceDirect, and SpringerLink reveals a steady increase in the volume of fibroin-
Figure 1. (a) Number of publication types on sericin in the three databases. (b) Comparison of the
number of publications in the three databases each year.
2.2. Fibroin-Based Studies
The findings presented in this meta-analysis are based on an extensive review of
the literature concerning fibroin. An analysis of data from prominent databases such as
PubMed, ScienceDirect, and SpringerLink reveals a steady increase in the volume of fibroin-
related publications over the past decade as shown in Figure 2. This trend highlights a
growing scientific interest, particularly in the fields of biomaterials, tissue engineering,
and drug delivery systems. Research articles represent the majority of publications across
these databases, indicating a significant level of experimental engagement with fibroin.
Notably, the diversity of publication types, including review articles, book chapters, and
technical reports, reflects the interdisciplinary nature of fibroin research, which spans
various domains such as materials science, biomedical engineering, and pharmacology.
PubMed showcases a stronger focus on the biomedical applications of fibroin, such as its
biocompatibility and potential for drug delivery, while ScienceDirect and SpringerLink
encompass a broader range of industrial applications, including textiles and environmental
sustainability. Furthermore, preliminary citation analysis suggests that key articles focusing
on the biomedical applications of fibroin are frequently cited, underscoring their significant
scientific impact and relevance. This analysis not only highlights the robust engagement
with fibroin-related studies, similar to those conducted on sericin, but also reveals emerging

J. Funct. Biomater. 2024,15, 322 4 of 36
trends and opportunities for future research, particularly in exploring fibroin’s full potential
in novel applications and addressing existing knowledge gaps in non-medical sectors. In
conclusion, fibroin-related studies have historically dominated the landscape of silk-related
publications, often overshadowing discussions surrounding silk sericin. However, in recent
years, there has been a noticeable shift in focus toward sericin, an underutilized protein,
highlighting its growing importance and potential applications. As evidenced by Table 2,
the number of studies on silk-related topics exceeds 38,000, further confirming the disparity
in attention between fibroin and sericin. This growing interest in sericin indicates an
opportunity for future research to explore its unique properties and applications alongside
fibroin, paving the way for a more balanced understanding of both proteins in the field
of biomaterials.
J. Funct. Biomater. 2024, 15, x FOR PEER REVIEW 5 of 38
(a)
(b)
Figure 2. (a) Number of publication types on fibroin in the three databases. (b) Comparison of the
number of publications in the three databases each year.
3. Silk Sericin Structure and Properties
3.1. Chemical Composition and Structure
Sericin, a protein extracted from silk, is known to be a “gluelike” protein since it holds
the two fibroin filaments together, as shown in Figure 3 [2]. It is a globular protein; it
consists of a random coil and β-sheets. Several factors affect the transition of sericin from
random-coil structure to β-sheets. It is an easily occurring phenomenon in response to
temperature, humidity, and mechanical properties. Sericin is soluble in water at tempera-
tures from 50 °C and above [3]. However, at lower temperatures, sericin’s solubility de-
creases gradually; hence, the conversion of the random coil into β-sheets occurs, leading
to the formation of a gel [2]. Kweon et al. studied the effect of poloxamer, a polymeric
surfactant, on the gelation of sericin. The results showed that the addition of the polox-
amer accelerated the change in sericin’s conformation from random coil to β-sheets. Also,
it showed that the gelation of sericin runs faster with higher concentrations of sericin and
Figure 2. (a) Number of publication types on fibroin in the three databases. (b) Comparison of the
number of publications in the three databases each year.

J. Funct. Biomater. 2024,15, 322 5 of 36
Table 2. Types and numbers of published studies on fibroin in online libraries.
Libraries PubMed Science Direct SpringerLink
Articles 6001 Research articles 7495 Articles 4783
Full Texts 5252 Book chapters 2325 Research articles 3210
Associated Data 1558 Encyclopedia 228 Chapters 2650
Reviews 415 Review articles 3562 Reference work entry 382
Systematic Reviews 10 Conference
abstracts 248 Conference papers 115
Randomized
controlled trials 4 - - Protocol 51
Clinical Trials 5 - - - -
Meta-analysis 1 - - - -
3. Silk Sericin Structure and Properties
3.1. Chemical Composition and Structure
Sericin, a protein extracted from silk, is known to be a “gluelike” protein since it holds
the two fibroin filaments together, as shown in Figure 3[
2
]. It is a globular protein; it consists
of a random coil and
β
-sheets. Several factors affect the transition of sericin from random-
coil structure to
β
-sheets. It is an easily occurring phenomenon in response to temperature,
humidity, and mechanical properties. Sericin is soluble in water at temperatures from 50
◦
C
and above [
3
]. However, at lower temperatures, sericin’s solubility decreases gradually;
hence, the conversion of the random coil into
β
-sheets occurs, leading to the formation of a
gel [
2
]. Kweon et al. studied the effect of poloxamer, a polymeric surfactant, on the gelation
of sericin. The results showed that the addition of the poloxamer accelerated the change
in sericin’s conformation from random coil to
β
-sheets. Also, it showed that the gelation
of sericin runs faster with higher concentrations of sericin and higher temperatures [
3
].
Takasu et al., in chromatographic analysis of sericin, rationalized that the reason sericin in
the silk gland is soluble in water, and that after being spun and dried it is not soluble, is
that sericin molecules form
β
-sheets during the drying process, which renders them less
soluble than the amorphous form [4].
J. Funct. Biomater. 2024, 15, x FOR PEER REVIEW 6 of 38
higher temperatures [3]. Takasu et al., in chromatographic analysis of sericin, rationalized
that the reason sericin in the silk gland is soluble in water, and that after being spun and
dried it is not soluble, is that sericin molecules form β-sheets during the drying process,
which renders them less soluble than the amorphous form [4].
Figure 3. Chemical structure of sericin surrounding fibroin fibers from Bombyx mori silkworm.
Sericin is a hydrophilic protein characterized by a high content of hydroxyl groups,
carboxyl groups, and polar amino acids. While serine governs the sericin amino acid con-
tent, 17 other amino acids are present. Those are alanine, arginine, aspartic acid, cysteine,
glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine,
proline, threonine, tryptophan, tyrosine, and valine [5]. This intricate amino acid makeup
plays a pivotal role in defining sericin’s variants, namely SER-1, SER-2, and SER-3, each
characterized by unique amino acid contents and variable molecular weights [5]. The syn-
thesis of sericin unfolds within the silk gland of Bombyx mori, a process intricately linked
to its molecular composition. Considering the morphological and functional differences,
the silk gland is divided into three parts, as shown in Figure 4, namely the anterior silk
gland (ASG), which constitutes the excretory duct; the middle silk gland (MSG), which
secretes three types of sericin; and the posterior silk gland (PSG) that secretes fibroin [2].
At the top end of the gland, there is a head, known as the spinneret, which is the fiber-
spinning entity.
Figure 3. Chemical structure of sericin surrounding fibroin fibers from Bombyx mori silkworm.

J. Funct. Biomater. 2024,15, 322 6 of 36
Sericin is a hydrophilic protein characterized by a high content of hydroxyl groups,
carboxyl groups, and polar amino acids. While serine governs the sericin amino acid
content, 17 other amino acids are present. Those are alanine, arginine, aspartic acid, cysteine,
glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine,
proline, threonine, tryptophan, tyrosine, and valine [
5
]. This intricate amino acid makeup
plays a pivotal role in defining sericin’s variants, namely SER-1, SER-2, and SER-3, each
characterized by unique amino acid contents and variable molecular weights [
5
]. The
synthesis of sericin unfolds within the silk gland of Bombyx mori, a process intricately linked
to its molecular composition. Considering the morphological and functional differences, the
silk gland is divided into three parts, as shown in Figure 4, namely the anterior silk gland
(ASG), which constitutes the excretory duct; the middle silk gland (MSG), which secretes
three types of sericin; and the posterior silk gland (PSG) that secretes fibroin [
2
]. At the top
end of the gland, there is a head, known as the spinneret, which is the
fiber-spinning entity.
J. Funct. Biomater. 2024, 15, x FOR PEER REVIEW 7 of 38
Figure 4. Representative sketch of the silk gland of Bombyx mori silkworm.
The middle gland was subdivided into four distinct parts according to the density and
morphology of the sericin synthesized and secreted [2]. Figure 5 provides photomicro-
graphs of these distinct regions, highlighting the cytoplasm (Cy), nuclei (indicated by ar-
rows), and lumen (Lu), thereby illustrating the structural characteristics essential for un-
derstanding silk production.
Figure 5. Photomicrographs of different regions (a) anterior, (b) middle, and (c) posterior, stained
with hematoxylin and eosin. Cytoplasm (Cy), nucleus (arrows), and lumen (Lu). Adapted from
[Kunz, R.I.; Brancalhão, R.M.C.; Ribeiro, L.D.F.C.; Natali, M.R.M. Silkworm Sericin: Properties and
Biomedical Applications. BioMed Res. Int. 2016, 2016, 1–19]. Available online:
doi:10.1155/2016/8175701 (accessed on 17 October 2024) [2].
The amino acid composition of the sericin protein has been extensively reported in
the literature. In Table 3 below, six studies were reported in chronological order showing
the different sericin amino acid composition analyses over the years. In addition, in the
last column, an average of the percentage values was reported for an overall evaluation
purpose.
Figure 4. Representative sketch of the silk gland of Bombyx mori silkworm.
The middle gland was subdivided into four distinct parts according to the density
and morphology of the sericin synthesized and secreted [
2
]. Figure 5provides photomi-
crographs of these distinct regions, highlighting the cytoplasm (Cy), nuclei (indicated by
arrows), and lumen (Lu), thereby illustrating the structural characteristics essential for
understanding silk production.
J. Funct. Biomater. 2024, 15, x FOR PEER REVIEW 7 of 38
Figure 4. Representative sketch of the silk gland of Bombyx mori silkworm.
The middle gland was subdivided into four distinct parts according to the density and
morphology of the sericin synthesized and secreted [2]. Figure 5 provides photomicro-
graphs of these distinct regions, highlighting the cytoplasm (Cy), nuclei (indicated by ar-
rows), and lumen (Lu), thereby illustrating the structural characteristics essential for un-
derstanding silk production.
Figure 5. Photomicrographs of different regions (a) anterior, (b) middle, and (c) posterior, stained
with hematoxylin and eosin. Cytoplasm (Cy), nucleus (arrows), and lumen (Lu). Adapted from
[Kunz, R.I.; Brancalhão, R.M.C.; Ribeiro, L.D.F.C.; Natali, M.R.M. Silkworm Sericin: Properties and
Biomedical Applications. BioMed Res. Int. 2016, 2016, 1–19]. Available online:
doi:10.1155/2016/8175701 (accessed on 17 October 2024) [2].
The amino acid composition of the sericin protein has been extensively reported in
the literature. In Table 3 below, six studies were reported in chronological order showing
the different sericin amino acid composition analyses over the years. In addition, in the
last column, an average of the percentage values was reported for an overall evaluation
purpose.
Figure 5. Photomicrographs of different regions (a) anterior, (b) middle, and (c) posterior, stained
with hematoxylin and eosin. Cytoplasm (Cy), nucleus (arrows), and lumen (Lu). Adapted from
[Kunz, R.I.; Brancalhão, R.M.C.; Ribeiro, L.D.F.C.; Natali, M.R.M. Silkworm Sericin: Properties and
Biomedical Applications. BioMed Res. Int. 2016,2016, 1–19]. Available online: https://doi.org/10.115
5/2016/8175701 (accessed on 17 October 2024) [2].

J. Funct. Biomater. 2024,15, 322 7 of 36
The amino acid composition of the sericin protein has been extensively reported in the
literature. In Table 3below, six studies were reported in chronological order showing the
different sericin amino acid composition analyses over the years. In addition, in the last
column, an average of the percentage values was reported for an overall evaluation purpose.
Table 3. Amino acid content of silk sericin for various references and their respective averages.
Amino-Acid 2000 [6] 2006 [7] 2009 [8] 2014 [9] 2015 [10] 2018 [11] Average
Ala 4.60 4.30 3.86 4.30 ND * 3.28 4.07
Arg 2.80 4.90 6.16 3.60 11.95 4.71 5.69
Asp 19.10 18.80 17.64 14.80 14.00 11.52 15.98
Cyst <0.05 0.30 ND * 0.10 ND * 0.03 0.14
Glu 4.10 7.20 7.31 3.40 3.30 2.91 4.70
Gly 12.20 10.70 9.89 14.70 23.20 12.60 13.88
His 0.90 1.70 1.81 1.20 1.13 2.05 1.47
Ile 1.40 1.30 1.04 0.70 0.91 0.34 0.95
Leu 0.60 1.70 1.44 1.40 2.08 1.05 1.38
Lys 10.20 2.10 3.05 2.40 3.18 2.33 3.88
Met <0.05 0.50 0.11 ND * 0.77 0.13 0.38
Phe 0.40 1.60 1.08 0.30 1.29 0.53 0.87
Pro 0.80 1.20 0.59 0.70 ND 0.59 0.78
Ser 30.40 27.30 32.74 37.3 21.56 40.51 31.64
Thr 6.00 7.50 5.51 8.70 7.04 8.45 7.20
Trp ND * 0.40 ND * ND * ND * ND * 0.40
Tyr 3.80 4.60 4.63 2.60 6.23 5.42 4.55
Val 2.60 3.80 3.14 3.60 3.36 3.56 3.34
Values are shown in Mol (%).* ND: not determined.
3.2. Physical Properties and Characteristics
Sericin can be classified according to two different parameters: solubility and molecu-
lar weight.
3.2.1. Solubility
Previously, sericin was classified into three different fractions, namely Sericin A,
Sericin B, and Sericin C [
12
]. The examination of the amino acid composition of sericin
was performed using paper partition chromatography. Sericin A, the one present in the
outermost layer of the cocoon, is soluble in warm water, consists of almost 17.2% nitrogen,
and the majority of its amino acids are serine, threonine, glycine, and aspartic acid. Sericin
B is the one present in the intermediate layer; it consists of 16.8% nitrogen and has the
same amino acids as Sericin A, in addition to tryptophan. Sericin C, which is the one found
in the innermost layer, is insoluble in hot water and has a lower nitrogen content, 16.6%,
compared to Sericin A and B. This fraction consists of the same amino acid content as
A and B, in addition to proline. It should be noted that Sericin C can be removed from
fibroin by treating it with a hot solution of an acid or an alkali. Sericin degrades easily due
to its sensitivity to changes in pH and temperature, and its ability to dissolve in various
solvents. Maintaining sericin’s structure is a challenge, when it comes to utilizing it in the
synthesis of sericin-based materials. The reason lies behind the conventional degumming
procedures which utilize elevated temperatures/pressures, and/or alkaline, which lead to
sericin degradation [5].
3.2.2. Molecular Weight
Silk sericin exhibits a spectrum of molecular weights influenced by various factors,
with the primary determinant being its source. Whether extracted from natural sources,
such as Bombyx mori cocoons, or synthesized through biotechnological techniques like re-
combinant DNA technology [
5
], these distinct methods contribute to variations in sericin’s
molecular weight. Additionally, the specific extraction techniques used for isolating sericin

J. Funct. Biomater. 2024,15, 322 8 of 36
from natural sources play a crucial role in determining its molecular weight. The molecular
weight is affected by several variables, including extraction methods, temperature, pH, and
processing time. This combination of factors results in a diverse molecular weight range
for extracted sericin, spanning from 10 to 400 kDa [
13
]. Numerous extraction methods
from silk cocoons contribute to this variability, encompassing high-temperature processes
with [
14
] and without [
15
] high pressure, utilization of urea [
14
], acids [
14
], alkalis [
14
],
enzymes [
15
], and microwave-assisted extraction [
16
]. With elevated temperatures and acid,
extractions result in sericin with molecular weights of 35–150 kDa, and the alkaline extrac-
tion leads to molecular weights of 15–75 kDa. As Bascou et al. previously reported, water
breaks down the peptide bonds of sericin, leading to its hydrolysis. Similarly in alkaline
environments, the presence of alkalis further reduces its molecular weight. Additionally,
elevated temperatures and high pressure accelerate the hydrolysis of the sericin macro-
molecule into smaller peptides. Furthermore, microwave heating penetrates deeper into
the matrix and leads to greater hydrolysis of sericin, while steam heating methods result
in the preservation of higher molecular weight fractions [
16
]. However, sericin extracted
using urea is the only method that has shown different bands between 10 and >225 kDa
using sodium–dodecyl sulfate–polyacrylamide gel electrophoresis analysis (SDS-PAGE).
Nonetheless, the chemically produced sericin by the recombinant protein method has a
molecular weight significantly lower than the one of the extracted sericin, which is almost
25 kDa [
17
]. Table 4below outlines the impact of various common extraction techniques
on the molecular weight of sericin. The section on extraction techniques provides detailed
information about previously employed methods. As mentioned in a published study on
the applications of sericin in biomaterials, it was conveyed that high molecular weight
sericin exhibits functionalities in functional biomembranes, hydrogels, and functional fibers
and fabrics. Nevertheless, the lower molecular weight sericin is applied in the cosmetic,
health, and medical industries [18].
Table 4. The different sericin molecular weights according to the extraction/production method and
their relative applications.
Method of Extraction/Production Molecular Weight (kDa) References
High temperature 100–200 [15]
High temperature–high pressure 25–150 [14]
Urea-based 10–225 [14]
Acid-based 50–150 [14]
Alkali-based 15–75 [14]
Enzymatic 5–25 [19]
Recombinant protein ≈25 [5]
3.3. Biophysical Characteristics
Sericin has emerged as a versatile biomaterial with diverse properties that enable
its application across a wide range of fields. Biocompatibility is a key characteristic of
materials intended for medical and biological use, as it refers to the ability of a material
to interact with biological systems without triggering an adverse immune response [
20
].
Sericin’s exceptional biocompatibility ensures minimal immunological reactions when in
contact with living tissues, thus reducing the risks of inflammation or rejection [
21
]. This
makes sericin particularly suitable for biomedical applications such as wound healing,
tissue engineering, and drug delivery systems [
22
]. In addition to its biocompatibility,
sericin’s inherent biodegradability [
23
] aligns well with environmentally friendly practices.
It can be naturally broken down by proteolytic enzymes in biological systems, such as pro-
teases, which hydrolyze sericin’s peptide bonds into smaller peptides and amino acids [
23
].
However, the long-term effects of sericin in biological systems remain unknown. This is
primarily because further studies are needed to understand the impact of the byproducts of
sericin hydrolysis. These byproducts, along with their reactivity and potential interactions
with bioactive compounds in the body, require thorough investigation to ensure the safety

J. Funct. Biomater. 2024,15, 322 9 of 36
and efficacy of sericin in biological systems in the long term. Sericin also exhibits a range of
functional properties beyond biocompatibility and biodegradability. Its anti-inflammatory,
antibacterial, antioxidant, and UV-protective capabilities open up further applications in
skin care, wound healing, food packaging, and textiles. Sericin’s anti-inflammatory activity
is associated with its ability to modulate the release of inflammatory cytokines, such as
interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-
α
), which are key mediators
of inflammation [
22
,
24
]. Additionally, sericin’s antibacterial efficacy is attributed to its
cysteine content. Cysteine, through its sulfhydryl group, forms weak hydrogen bonds with
oxygen or nitrogen, resulting in reactive compounds that interfere with the enzymatic and
metabolic processes vital to microorganisms, thereby providing sericin with antibacterial
properties [
22
,
25
]. Its antioxidant activity is linked to its ability to scavenge reactive oxygen
species (ROS), with high levels of serine and threonine enabling effective chelation of
transition metal ions like copper and iron [
26
]. These antioxidant properties help miti-
gate oxidative stress, a key factor in skin aging, thus contributing to sericin’s anti-aging
effects [
27
]. Furthermore, the presence of arginine and alanine in sericin’s structure allows
it to bind tyrosinase, giving it anti-tyrosinase activity and positioning sericin as an effective
agent in skin-related applications [
21
]. Figure 6illustrates the process of extracting sericin
from Bombyx mori cocoons and its transformation into final products for use in various
fields. The figure highlights the extraction techniques employed and the key properties
that make sericin a valuable biomaterial.
J. Funct. Biomater. 2024, 15, x FOR PEER REVIEW 10 of 38
byproducts of sericin hydrolysis. These byproducts, along with their reactivity and poten-
tial interactions with bioactive compounds in the body, require thorough investigation to
ensure the safety and efficacy of sericin in biological systems in the long term. Sericin also
exhibits a range of functional properties beyond biocompatibility and biodegradability.
Its anti-inflammatory, antibacterial, antioxidant, and UV-protective capabilities open up
further applications in skin care, wound healing, food packaging, and textiles. Sericin’s
anti-inflammatory activity is associated with its ability to modulate the release of inflam-
matory cytokines, such as interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-α),
which are key mediators of inflammation [22,24]. Additionally, sericin’s antibacterial effi-
cacy is aributed to its cysteine content. Cysteine, through its sulydryl group, forms
weak hydrogen bonds with oxygen or nitrogen, resulting in reactive compounds that in-
terfere with the enzymatic and metabolic processes vital to microorganisms, thereby
providing sericin with antibacterial properties [22,25]. Its antioxidant activity is linked to
its ability to scavenge reactive oxygen species (ROS), with high levels of serine and threo-
nine enabling effective chelation of transition metal ions like copper and iron [26]. These
antioxidant properties help mitigate oxidative stress, a key factor in skin aging, thus con-
tributing to sericin’s anti-aging effects [27]. Furthermore, the presence of arginine and al-
anine in sericin’s structure allows it to bind tyrosinase, giving it anti-tyrosinase activity
and positioning sericin as an effective agent in skin-related applications [21]. Figure 6 il-
lustrates the process of extracting sericin from Bombyx mori cocoons and its transfor-
mation into final products for use in various fields. The figure highlights the extraction
techniques employed and the key properties that make sericin a valuable biomaterial.
Figure 6. Sericin’s various characteristics and applications. (a) Silkworm Bombyx mori. feeding on
mulberry leaves; (b) Cocoons produced by Bombyx mori. silkworms; (c) Sericin powder recovered
from different extraction procedures; (d) Fibroin fibers. HTPT: high temperature, high pressure. R-
protein: recombinant protein.
4. Extraction Methods
4.1. Degumming Process Overview
The extraction method, known as degumming, entails the meticulous separation of
the silk sericin layer, colloquially referred to as gum, from silk fibroin fibers. This intricate
Figure 6. Sericin’s various characteristics and applications. (a) Silkworm Bombyx mori. feeding on
mulberry leaves; (b) Cocoons produced by Bombyx mori. silkworms; (c) Sericin powder recovered
from different extraction procedures; (d) Fibroin fibers. HTPT: high temperature, high pressure.
R-protein: recombinant protein.

J. Funct. Biomater. 2024,15, 322 10 of 36
4. Extraction Methods
4.1. Degumming Process Overview
The extraction method, known as degumming, entails the meticulous separation of
the silk sericin layer, colloquially referred to as gum, from silk fibroin fibers. This intricate
procedure involves the hydrolytic or enzymatic cleavage of sericin’s peptide bonds, subse-
quently facilitating its extraction from the silk fibroin matrix. Various methods, including
chemical, thermal, and biological, have been investigated to achieve the successful extrac-
tion of sericin. After degumming, further purification methods can be applied to isolate
pure sericin.
4.2. Conventional Extraction Methods
Degumming silk by boiling off in soap solutions, including the prevalent use of Mar-
seille soap derived from olive oil, has been practiced for over two centuries. The soap’s
hydrolysis produces alkali, which aids in the breakdown of sericin from the silk thread;
subsequently, the sericin is dissolved in water through the emulsification action of the
soap. Typically, a degumming time of 90–120 min at boiling temperature is sufficient, with
Marseille soap preferred for its high degree of hydrolysis. Despite its effectiveness, the
use of Marseille soap poses economic challenges [
28
], including potential water quality
issues affecting silk quality and the need for high soap quantities, leading to environmental
concerns [
29
]. To address these challenges, mixtures of soap and alkali have been explored,
accelerating degumming while mitigating pollution concerns, albeit with susceptibility to
hard water. Various alkalis, including sodium silicate and sodium carbonate, have been in-
vestigated for their effectiveness in enhancing the degumming process and maintaining pH
levels conducive to efficient degumming [
19
,
30
–
36
]. However, the efficacy of this method is
compromised by the challenging task of sericin retrieval from the soap solution, rendering
the recovery process intricate. The resultant wastewater from the degumming process
contains residues of sericin, salts, and soap, necessitating comprehensive purification and
prompting the exploration of alternative degumming strategies.
4.3. Chemical Extraction Methods
Industrial practices often adopt simplified approaches, such as degumming through
the use of various chemical treatments, which circumvent the use of expensive additives
like Marseille soaps. Acids (citric, tartaric, succinic, etc.) or bases (sodium carbonate,
sodium phosphate, sodium silicate, sodium hydrosulfite, etc.) are used to extract the
sericin from silk. These chemicals hydrolyze sericin by breaking the peptide bonds between
amino acids, resulting in the release of sericin into an alkaline or acidic solution, where
it is highly soluble [
37
–
40
]. The use of acids and bases to extract sericin can significantly
degrade the protein [
38
]. On the contrary, the urea degradation extraction method, often
supplemented with 2-mercaptoethanol, demonstrates a reduced degradative impact on
sericin. This approach allows for the extraction of approximately 95% of the total sericin
content within the fiber without inducing damage. However, despite its efficacy, this
method is characterized by its high cost and time-consuming nature [
39
]. Additionally,
sericin obtained through urea-based extraction exhibits high toxicity toward cells [
41
].
Despite some advancements, challenges persist in recovering high-quality sericin due to
the residual chemical impurities inherent in the degumming process [
13
]. Moreover, the
environmental ramifications of these methodologies warrant attention, as the presence of
chemical remnants in residual water compromises ecological integrity [13].
4.4. Biological Extraction Methods
Alternatively, enzymatic approaches have emerged as a favorable strategy for sericin
degumming, primarily due to their inherent efficiency in energy consumption [
19
,
34
,
42
,
43
].
The utilization of enzymes in degumming is connected to the discovery of cocoonase, a class
of proteinases adept at breaking down sericin bindings. Various enzymes such as trypsin,
papain, and bacterial enzymes have been prominently employed for the degumming

J. Funct. Biomater. 2024,15, 322 11 of 36
process [
44
]. Trypsin, a proteolytic enzyme, targets the peptide bonds between the carboxyl
group of lysine or arginine and adjacent amino acids, a process facilitated by sericin’s
elevated lysine and arginine content. Papain, with its broad specificity toward polypeptides,
also serves as an effective agent for cocoon degumming [
45
]. Furthermore, alcalase, a
bacterial enzyme, along with several fungal protease enzymes, have been standardized and
proven economically viable, devoid of chemical hazards [
44
]. The concentration of enzymes
and duration of treatment significantly impact the process kinetics. Additionally, the
chemical properties of soluble sericin peptides vary depending on the enzyme employed.
Although marginally pricier than the aforementioned techniques, this method demands less
energy, rendering it more environmentally sustainable [
35
]. The concurrent utilization of
the enzymes savinase and alcalase, along with ultrasound, has also been explored for sericin
extraction from silk fibers [
28
]. This approach enhances the efficacy of the degumming
process with prolonged treatment duration. However, the authors have not examined
the integrity of the isolated sericin [
28
]. Notably, an extracellular protease derived from
Bacillus sp. exhibits remarkable specificity in sericin removal under mildly alkaline pH
conditions. While the fibrous structure remains unaltered, sericin undergoes degradation
into peptides measuring 10–12 kDa in size, underlining the selective action of protease
enzymes in degumming processes [
43
]. Similarly, a recently isolated thermostable alkaline
serine protease from Bacillus halodurans displays superior degumming efficacy compared to
commercial alcalase protease [46].
4.5. Thermal Extraction Methods
Furthermore, thermal extraction primarily involved boiling cocoons in hot water, a
method appreciated for its straightforwardness and minimal chemical intervention [
8
]. The
utilization of hot water, typically between 80
◦
C and 100
◦
C under atmospheric pressure,
has garnered significant attention, while the development of high-pressure techniques,
facilitated by lab-scale autoclave machinery, has further expanded the horizons of silk
degumming methodologies [
13
,
47
,
48
]. Regardless of the specific technique employed,
a common assurance prevails—extraction of sericin by boiling in water under ambient
or increased pressure offers the distinct advantage of ensuring the absence of impurities
and direct use of recovered sericin without dialysis [
13
]. While thermal extraction may
result in certain levels of sericin degradation, particularly with elevated temperatures or
prolonged exposure, sericin maintains its exceptional properties, rendering it the most
widely employed approach [
49
]. Variations in extraction conditions, such as temperature,
pressure, and heating duration, play a significant role in determining the molecular weight
of extracted sericin from cocoons. In essence, these conditions offer a means to regulate the
molecular weight of sericin during extraction [42].
4.6. Modern Extraction Methods
Emerging technologies have been devised to extract sericin from fibroin in a more en-
vironmentally friendly, efficient, and sustainable manner. These include methods utilizing
infrared heat, microwave, steam treatment, carbon dioxide supercritical fluid, and ultra-
sonication [
16
,
31
,
35
,
42
,
47
–
50
]. Explorations into those treatments have offered promising
avenues for reducing water consumption during extraction, aligning with sustainability
objectives. However, it is worth noting that the resulting sericin may exhibit variances
in molecular weights contingent upon extraction parameters such as temperature and
duration [
47
]. A recent breakthrough study showcased the efficacy of infrared heating in
achieving complete removal of sericin from raw silk, yielding a protein content of superior
quality compared to conventional methods [
47
]. This innovative approach leveraged radi-
ation heating, which directly transferred energy to the material through electromagnetic
waves, thereby facilitating sericin detachment and enhancing solubility in water. In this
process, water molecules act as abrasives during energy transfer by electromagnetic waves,
thereby enhancing the sericin shedding. Further on, findings from one study [
16
] suggested
that microwave degumming offers several advantages, including short extraction time, low

J. Funct. Biomater. 2024,15, 322 12 of 36
energy consumption, and absence of chemical pollution. In comparison to other degum-
ming methods like acid and alkaline-based, boiling, high-temperature, and high-pressure,
microwave degumming emerges as the most effective technique together with infrared
heating. Since infrared and microwave heating eliminate the need for additional chemicals
in the degumming process, their solutions are conducive to achieving high-purity and cost-
effective extraction of sericin. Furthermore, spectroscopic analyses revealed that infrared
extraction methods resulted in minimal denaturation and degradation of sericin molecules
compared to conventional autoclave extraction techniques, underscoring the potential
of infrared heating in mitigating protein degradation [
47
]. Steam treatment effectively
removes sericin from silk fibers using pressurized steam without any chemicals, minimiz-
ing water pollution and consumption, maintaining desirable physicochemical properties,
and being more energy-efficient and economical compared to conventional methods [
35
].
Moreover, the carbon dioxide supercritical fluid method offers an environmentally stable
alternative to conventional extraction methods, effectively cleanly removing sericin pro-
tein [
50
]. Similarly, ultrasonic extraction was proven to efficiently and environmentally
remove sericin from fibroin, enhancing degumming rate and fiber quality, particularly at
lower temperatures, compared to conventional thermal methods [42].
4.7. Sericin Extraction: Impact on Environment, Economy, and Functionality
Each extraction method has distinct advantages and limitations, as summarized in
Table 5. Acidic and basic extraction methods, while effective, significantly degrade the
sericin structure, resulting in a loss of functionality and requiring further purification to
remove chemical residues [
38
], as discussed in Section 4.3. Additionally, these methods raise
environmental concerns due to the toxic waste generated, necessitating careful disposal,
thereby increasing costs and impacting sustainability. Urea-based extraction methods
are time-consuming and costly, as noted in Section 4.3, and they pose environmental
challenges due to the toxicity of urea and the hazardous waste produced [
39
]. In contrast,
thermal extraction using hot distilled water is the most employed method due to its
simplicity and lower environmental impact. This approach is highlighted in Section 4.6,
where boiling cocoons in water are noted for their minimal chemical intervention and the
ability to produce sericin free from impurities [
8
]. Although it may cause some protein
degradation, especially at high temperatures or with prolonged exposure [
49
], the absence
of chemical additives makes this method economically feasible and scalable, leading to its
wide acceptance in industrial applications. Recently, more sustainable techniques, such
as infrared heating, supercritical CO
2
extraction, and ultrasound extraction, have been
explored [
31
,
42
]. These methods reduce reliance on harmful chemicals, enhancing their eco-
friendliness. However, as noted in Section 4.5, they require specialized equipment, which
increases initial costs and may hinder widespread adoption until their economic viability
improves. To explore the functional characteristics of sericin, it is important to examine
the conformational changes in its secondary structure that result from various extraction
methods. Conventional and alkali-degradation extraction techniques yield sericin with a
composition of
α
-helices, random coils, and turns. In contrast, sericin extracted through
autoclaving lacks
α
-helical structures [
51
]. Notably, regardless of the extraction method
employed, sericin consistently exhibits a negative zeta potential, with urea-extracted sericin
displaying the highest negative charge, followed by acid-degraded, heat-degraded, and
alkali-degraded sericin [
39
]. Research by Aramwit et al. [
39
] indicates that serine is the most
abundant amino acid in sericin across all extraction methods, followed by aspartic acid and
glycine. Thermal-extracted sericin shows significantly higher levels of methionine, whereas
urea-extracted sericin has notably lower tyrosine content. Furthermore, extraction methods
influence the presence of secondary metabolites; for instance, thermal extraction results
in higher total phenol content, while urea extraction yields lower levels. Acid-degraded
sericin is characterized by the highest flavonoid content, in contrast to the lowest levels
found in alkali-degraded sericin [
51
]. The choice of extraction method significantly affects
the properties of sericin, thereby influencing its potential applications. The arrangement

J. Funct. Biomater. 2024,15, 322 13 of 36
of sericin’s amino acids, encompassing aggregation,
β
-sheet formation, and
β
-turns, can
impact cell behavior. Minimizing chemical degradation is essential for enhancing cell
growth and attachment, primarily due to the spatial arrangement of methionine and
cysteine residues [
5
]. Additionally, the amino acid composition of sericin plays a crucial
role in its biological properties and performance as a biomaterial. For example, sericin
with higher concentrations of serine and threonine demonstrates improved antioxidant
and photoprotective activities. Moreover, different extraction methods have been shown to
variably impact cell viability and collagen production [39].
Table 5. Different sericin extraction methods.
Degumming
Method Approach Advantages Disadvantages
Conventional Soaps and Alkalis •Effective.
•Sericin is highly degraded.
•Recovery is difficult.
•Time-consuming and high cost.
•It is not environmentally friendly.
•Effluent problems.
Chemical
Alkaline solutions
•Application on a large scale.
•Low cost.
•High yield.
•Sericin is highly degraded.
•Recovery is difficult.
•Purification steps are needed.
•It is not environmentally friendly.
•Effluent problems.
Acidic solutions •
Lower degree of degradation
than alkali degumming.
•Sericin is degraded.
•Purification steps are needed.
•It is not environmentally friendly.
•Effluent problems.
Urea (with or without
mercaptoethanol)
•Low degree of degradation.
•Effective.
•Purification steps are needed.
•Toxic to cells.
Biological Proteolytic enzymes
•Effective.
•Complete removal of SS.
•Environmentally
friendly/no effluent
problems
•High cost.
•Sericin is degraded.
•Time-consuming.
Thermal Boiling •Simple. •Sericin is degraded.
•Time-consuming.
HTHP (autoclave)
•No purification process is
required.
•Low cost.
•Low toxicity. Suitable for
safety evaluation.
•Environmentally
friendly/no effluent
problems
•Heat-caused degradation.

J. Funct. Biomater. 2024,15, 322 14 of 36
Table 5. Cont.
Degumming
Method Approach Advantages Disadvantages
Modern
Infrared •High yield and quality of
silk sericin. •Extra equipment needed.
Microwave
•Short extraction time.
•Lower energy consumption.
•Environmentally friendly.
•Commercial viability is limited.
Ultrasound
•Increased efficiency at lower
temperatures.
•Environmentally friendly.
•Higher equipment costs.
•Need for optimization.
Steam treatment
•Effective.
•Lower water consumption.
•Lower processing cost.
•Environmentally friendly.
•Lack of selectivity.
•The developed process may not be
suitable for industrial-scale mode
operation.
CO2supercritical fluid
•Improves efficiency, water,
and energy conservation.
•Less wastewater generation,
and low energy
consumption.
•Introduce chemicals, not
well-established in the industry.
5. Purification
After the initial degumming process, further isolation and purification steps are un-
dertaken to obtain purified sericin. Generally, after each degumming process, the extracted
sericin solution undergoes paper filtration to be separated from insoluble fibroin, followed
by centrifugation to further separate any remaining impurities. Precipitation methods,
such as acidulation precipitation, chemical coagulation, organic solvent precipitation, and
salting out can also be used, involving the addition of a precipitating agent to induce
the sericin protein to separate of solution, or using a freezing/thawing method [
52
–
55
].
Dialysis can be employed if chemical extraction methods are used, particularly those in-
volving sodium carbonate, citric acid, or urea [
42
,
43
]. Optionally, gel chromatography
can be applied for further purification based on molecular size, followed by membrane
filtration to remove smaller impurities [
56
]. However, precipitation methods pose chal-
lenges such as low recovery rates (around 40%) and increased risk of secondary pollution
due to the involvement of chemicals [
57
]. Once isolated, the sericin protein is typically
dissolved and the solution needs to be dried to obtain a stable powder or solid form. Drying
methods such as lyophilization and spray drying can be used to remove the water from
the sericin solution [
55
,
58
,
59
]. Although these techniques are widely utilized depending
on the desired level of purification, challenges remain in balancing recovery rates and
purity. In response to these limitations, membrane separation techniques, particularly
ultrafiltration (UF) and nanofiltration (NF), have emerged as promising alternatives for
obtaining higher recovery rates (above 80%) and higher purity of sericin protein [
15
,
33
,
60
].
The steps outlined in Figure 7enable the effective purification and refinement of sericin,
resulting in a high-quality product suitable for various industrial applications. Each stage
of the process is thoughtfully designed to maximize yield, enhance purity, and improve
efficiency while minimizing the degradation of the sericin protein.

J. Funct. Biomater. 2024,15, 322 15 of 36
J. Funct. Biomater. 2024, 15, x FOR PEER REVIEW 16 of 38
involving sodium carbonate, citric acid, or urea [42,43]. Optionally, gel chromatography
can be applied for further purification based on molecular size, followed by membrane
filtration to remove smaller impurities [56]. However, precipitation methods pose chal-
lenges such as low recovery rates (around 40%) and increased risk of secondary pollution
due to the involvement of chemicals [57]. Once isolated, the sericin protein is typically
dissolved and the solution needs to be dried to obtain a stable powder or solid form. Dry-
ing methods such as lyophilization and spray drying can be used to remove the water
from the sericin solution [55,58,59]. Although these techniques are widely utilized de-
pending on the desired level of purification, challenges remain in balancing recovery rates
and purity. In response to these limitations, membrane separation techniques, particularly
ultrafiltration (UF) and nanofiltration (NF), have emerged as promising alternatives for
obtaining higher recovery rates (above 80%) and higher purity of sericin protein [15,33,60].
The steps outlined in Figure 7 enable the effective purification and refinement of sericin,
resulting in a high-quality product suitable for various industrial applications. Each stage
of the process is thoughtfully designed to maximize yield, enhance purity, and improve
efficiency while minimizing the degradation of the sericin protein.
Figure 7. Sericin purification process overview.
6. Biological and Medical Applications
As described in Section 3, silk sericin is a versatile biomaterial suitable for various
biomedical applications due to its biocompatibility, biodegradability, and multifunctional
properties, including anti-inflammatory, antibacterial, antioxidant, anti-tyrosinase, and
anti-aging effects. This section will elaborate on these applications in detail. Figure 8 illus-
trates the comprehensive processing of regenerated sericin biomaterials and highlights
the various forms they can take for biomedical applications. Initially, the process involves
degumming to extract and dissolve sericin. The degumming solution, containing sericin,
is subjected to a salting-out method to precipitate the sericin, which is then dissolved in
distilled water to form a sericin solution. This solution undergoes dialysis to yield a re-
generated sericin solution, and spray-drying of this regenerated solution produces sericin
powder. Currently, silk biomaterials derived from this process are available in various
forms, including hydrogels [61–66], films [67–71], mats [72], scaffolds [62,73–75], sponges
[76], and particles [77–80], showcasing their versatility in biomedical applications.
Figure 7. Sericin purification process overview.
6. Biological and Medical Applications
As described in Section 3, silk sericin is a versatile biomaterial suitable for various
biomedical applications due to its biocompatibility, biodegradability, and multifunctional
properties, including anti-inflammatory, antibacterial, antioxidant, anti-tyrosinase, and
anti-aging effects. This section will elaborate on these applications in detail. Figure 8
illustrates the comprehensive processing of regenerated sericin biomaterials and highlights
the various forms they can take for biomedical applications. Initially, the process involves
degumming to extract and dissolve sericin. The degumming solution, containing sericin,
is subjected to a salting-out method to precipitate the sericin, which is then dissolved
in distilled water to form a sericin solution. This solution undergoes dialysis to yield
a regenerated sericin solution, and spray-drying of this regenerated solution produces
sericin powder. Currently, silk biomaterials derived from this process are available in
various forms, including hydrogels [
61
–
66
], films [
67
–
71
], mats [
72
], scaffolds [
62
,
73
–
75
],
sponges [
76
], and particles [
77
–
80
], showcasing their versatility in biomedical applications.
6.1. Drug Delivery Systems
Given their diverse structural features and excellent biocompatibility, silk proteins
find extensive applications as delivery systems for a wide range of bioactive molecules,
including drugs and various small molecules [
81
,
82
]. Sericin, with its amphiphilic nature
characterized by both polar side chains and hydrophobic domains, emerges as a versatile
vehicle capable of efficiently binding charged molecules [
83
]. Its prolonged half-life
in vivo
,
attributed to enhanced retention in kidney filtration, coupled with remarkable moisture
absorption and desorption abilities, highlights its crucial role in drug delivery [
84
]. Ad-
ditionally, sericin’s capacity to expand and contract further enhances its appeal in this
context [
85
]. Whether utilized in its pure state or blended with other polymers, sericin can
be customized for a variety of purposes, including the creation of implantable or injectable
materials such as matrices, particles, and hydrogels, thereby meeting specific needs and
requirements [
31
]. Several of these recent applications can be found in the accompanying
Table 6.

J. Funct. Biomater. 2024,15, 322 16 of 36
J. Funct. Biomater. 2024, 15, x FOR PEER REVIEW 17 of 38
Figure 8. Processing and types of regenerated sericin biomaterials.
6.1. Drug Delivery Systems
Given their diverse structural features and excellent biocompatibility, silk proteins
find extensive applications as delivery systems for a wide range of bioactive molecules,
including drugs and various small molecules [81,82]. Sericin, with its amphiphilic nature
characterized by both polar side chains and hydrophobic domains, emerges as a versatile
vehicle capable of efficiently binding charged molecules [83]. Its prolonged half-life in
vivo, aributed to enhanced retention in kidney filtration, coupled with remarkable mois-
ture absorption and desorption abilities, highlights its crucial role in drug delivery [84].
Additionally, sericin’s capacity to expand and contract further enhances its appeal in this
context [85]. Whether utilized in its pure state or blended with other polymers, sericin can
be customized for a variety of purposes, including the creation of implantable or injectable
materials such as matrices, particles, and hydrogels, thereby meeting specific needs and
requirements [31]. Several of these recent applications can be found in the accompanying
Table 6.
Figure 8. Processing and types of regenerated sericin biomaterials.

J. Funct. Biomater. 2024,15, 322 17 of 36
Table 6. Recent studies investigating sericin’s role in delivery systems.
Materials Medical Condition Cell/Drug Delivered Refs.
SS/PAC aUlcerative
Colitis Proanthocyanidins [77]
SS@FeS bBreast Cancer Nano agent [78]
SS-PLA cCancer Therapy Doxorubicin (DOX) [86]
SSC-NPs dCancer Phototherapy Chlorin e6 (Ce6) [87]
MR-SNC eBreast Cancer Resveratrol and Melatonin [88]
Sericin Microparticles-
MON
Metastatic
Lung Cancer Doxorubicin (DOX)
Genipin/sericin
hydrogels Ischemic Stroke neurotrophic cytokines
Zein/sericin
nanoblends Antitumor 5-Fluorouracil [89,90]
SS-NPs fCancer Immunotherapy Doxorubicin (DOX) and Indocyanine
green (ICG) [91]
Cispt-SNC gBreast Cancer Cisplatin [92]
Fucoidan and Sericin Chronic Inflammatory Diseases Diclofenac sodium (DS) [93]
a
Silk sericinproanthocyanidins composites,
b
Silk sericin–ferric sulfide nanoparticles,
c
Silk Sericin–Polylactide,
dSilk sericin-based nanoparticles, eMelatonin–resveratrol sericin-based nanocarrier, fSilk sericin-nanoparticles,
gCisplatin–sericin-based nanocarriers.
Sericin-based structures, primarily hydrogels, are often created through processes like
crosslinking, precipitation, chemical modification, or blending with other polymers. These
structures have shown promise in drug delivery applications. For instance, hydrogels
formed from sericin can serve as matrices for incorporating therapeutic agents, providing
sustained release profiles and targeted delivery to specific tissues or cells. Additionally,
the versatility of sericin allows for the modification of these structures to enhance their
drug-loading capacity, biocompatibility, and stability. Zhang et al. [
94
] utilized sericin in
conjunction with ionically cross-linked alginate to fabricate hydrogels capable of not only
hosting myoblast cells but also stimulating their proliferation, migration, and viability.
However, monitoring certain aspects of injectable hydrogels
in vivo
, such as drug release
kinetics and gel degradation, presents challenges. To address this, a study by Hardy
et al. [
81
] developed a sericin/dextran injectable hydrogel, which exhibited efficient drug
loading and controlled release of both macromolecular (horseradish peroxidase, HRP) and
small molecular (antitumor drug doxorubicin, DOX) drugs. Moreover, this hydrogel served
as a photoluminescence-trackable drug delivery system, as the sericin’s photoluminescence
directly and stably correlated with its degradation. This capability enabled long-term
in vivo
imaging and real-time monitoring of the remaining drug. Remarkably, a substantial
quantity of natural silk sericin was extracted directly from the silk glands of silkworm
mutants lacking fibroin in another study conducted by Zhang et al. [
94
]. This silk sericin (SS)
was then crosslinked with H
2
O
2
, resulting in a robust sericin hydrogel characterized by a
high elastic modulus. Unexpectedly, SS-H
2
O
2
(silk sericin crosslinked with H
2
O
2
) exhibited
exceptional mechanical resilience and durability, making it a promising candidate for
sustained-release drug delivery. Protein-based nanoparticles are highly efficient carriers for
the controlled release of pharmaceuticals or cells, as they degrade into non-toxic, absorbable
byproducts [
95
]. The chemical reactivity of sericin enables the production of drug carriers,
such as nanoparticles and microparticles, by facilitating the straightforward binding of
molecules [
31
]. In relation to that, one study [
79
] developed a novel siRNA delivery
system for treating laryngeal cancer. By synthesizing albumin–sericin nanoparticles with
different ratios of albumin and sericin, researchers addressed the challenge of delivering
siRNA effectively. These nanoparticles, modified with poly-L-lysine (PLL) and hyaluronic
acid (HA), successfully targeted laryngeal cancer cells and silenced overexpressed genes.

J. Funct. Biomater. 2024,15, 322 18 of 36
The optimized formulation achieved high siRNA entrapment efficiencies and effectively
inhibited cell growth and induced apoptosis.
Another study highlighted sericin nanoparticles’ potential as highly efficient carriers
for transporting bioactive compounds to specific target cells [
80
]. Researchers found that
silk sericin can be a promising bio-nanocarrier for resveratrol delivery. Resveratrol-loaded
sericin nanoparticles (RSV-loaded SP), measuring 200–400 nm in size, with negative charges,
were developed. Encapsulation varied with sericin concentration (0.6% and 1.0% w/v),
showing sustained resveratrol release over 72 h. These nanoparticles were non-cytotoxic
to the skin, inhibited colorectal adenocarcinoma cell growth, and were internalized by
cells. A recent study [
77
] aimed to expand silk sericin’s role as a drug carrier by devel-
oping a simple method for creating sericin-stabilized drug composites. Encapsulating
insoluble drugs like proanthocyanidins (PAC) into sericin achieved high drug loading and
uniform dispersion in water. The resulting SS/PAC composites showed notable antiox-
idant effects and biocompatibility, indicating potential for therapeutic use, especially in
treating conditions like ulcerative colitis. Another recent study [
78
] attempted to develop
a highly efficient photothermal nanoagent, SS@FeS, for tumor treatment. The nanoagent
exhibited excellent water dispersibility, high photothermal ability, and potent anticancer
performance by integrating natural sericin protein with ferric sulfide nanoparticles. It
efficiently entered cells, accumulating in lysosomes and mitochondria, where it induced
enhanced cytotoxicity against 4T1 tumor cells by damaging mitochondria. Additionally,
the nano agent demonstrated a fenton reaction, enhancing its photothermal therapy (PTT)
efficacy. These findings suggest the potential of SS@FeS as a promising candidate for pho-
tothermal agent-based tumor treatment. Moreover, a study [
91
] in 2023 aimed to use sericin
nanoparticles (SDINPs) to induce immunogenic cell death (ICD) in cancer therapy through
photothermal therapy (PTT). SDINPs delivered chemotherapeutic drugs and photosen-
sitizers to target cancer cells, showing enhanced therapeutic efficacy and PTT-mediated
ICD induction. Due to sericin’s impressive hydrophilicity, hydrophobic entities such as
cholesterol [
96
], polylactide [
86
], doxorubicin [
97
], and chlorin e6 [
87
] can be attached to
sericin to form amphiphilic conjugates. These conjugates could spontaneously assemble
into micelles, facilitating the delivery of pharmaceutical agents. In addition to its applica-
tions in drug and cell delivery, sericin also possesses potential as a contrast agent. It can
be linked with specific targeting ligands or imaging probes, facilitating targeted imaging
for various therapeutic purposes [
5
,
98
]. Sericin’s pH sensitivity stems from its highly
polar side groups, including hydroxyl, carboxyl, and amino functionalities. Researchers
have extensively explored its potential in developing smart delivery systems, particularly
pH-responsive ones. These systems offer notable advantages, allowing for precise control
over therapeutic compound release in response to external acidic or alkaline conditions.
This specificity enhancement not only improves efficacy but also minimizes potential side
effects [
90
,
91
]. The hydrazone bond, renowned for its pH-sensitive nature, has frequently
been employed in fabricating drug delivery systems based on sericin that responds to acidic
conditions [
86
,
88
,
92
,
97
]. A 2023 study developed a pH-responsive sericin-based nanocar-
rier (MR-SNC) for co-delivering resveratrol and melatonin to MCF-7 breast cancer cells [
88
].
Using flash-nanoprecipitation, MR-SNC was designed with various sericin concentrations
to exhibit pH-dependent behavior.
In vitro
studies confirmed significant pH-dependent
drug release, cellular uptake, and cytotoxicity, demonstrating its potential for controlled
release in acidic environments. Therefore, the study highlighted MR-SNC’s pH-dependent
charge reversal property, enhancing drug delivery specificity and efficacy in acidic tumor
microenvironments. In addition to the seminal works on this subject [
85
,
97
,
99
,
100
], there
have been subsequent developments inspired by prior research endeavors. The target of
another novel investigation [
86
] was to develop pH-responsive drug delivery materials
using sericin as a building block. Amphiphilic substances were synthesized by conjugat-
ing hydrophobic polylactide (PLA) with hydrophilic sericin using a bis-aryl hydrazone
linker. The pH-dependent drug release from SS-PLA nanoparticles was investigated using
doxorubicin (DOX) as a model drug. Results showed that the release rate of DOX was

J. Funct. Biomater. 2024,15, 322 19 of 36
slower at physiological pH (7.4) compared to pH 5.0, indicating pH dependency. Therefore,
this investigation emphasized the promising role of sericin-based amphiphilic materials
as effective drug carriers for cancer therapy, particularly highlighting their pH-responsive
characteristics. A study in 2024 developed pH-sensitive sericin-based nanocarriers (SNCs)
for controlled cisplatin delivery in breast cancer therapy [
92
]. These SNCs, produced via
nanoprecipitation, encapsulated cisplatin and displayed a crucial charge-reversal property
for effective drug release. Optimizing sericin concentration, they achieved suitable size
and high drug encapsulation for efficient cellular uptake. Physicochemical analyses con-
firmed SNCs and Cispt-SNCs’ suitability for effective drug delivery. Interaction between
Cispt-SNCs and cells induces apoptosis, highlighting their potential for targeted therapy.
6.2. Tissue Engineering
Given its established efficacy in the cosmetic sector, as outlined in Section 7, silk sericin
was first used in skin tissue engineering within biomedical applications. Furthermore,
owing to its recognized mitogenic and osteogenic properties, sericin-based biomaterials
have broadened their scope to encompass tissue engineering applications in bone, cartilage,
cardiac, neural, and muscle tissues. As sericin’s diverse potential emerges, it is progres-
sively used in various areas including inflammatory disorders, bio-adhesion, hemostasis,
and beyond. Sericin, when cross-linked with various polymers to form gels, offers versatile
applications, particularly in wound healing. Its biocompatibility ensures minimal immuno-
logical reactions, distinguishing it from other biomaterials. Among contemporary wound
dressings, sericin-based films [
67
–
71
], hydrogels [
61
–
64
], and scaffolds [
62
,
73
–
75
] are fa-
vored choices due to their ability to serve as physical barriers and absorb exudates. The
recently reported works on sericin-based wound healing systems are highlighted in Table 7.
In the context of films, which serve as highly flexible and elastic structures facilitating gas
exchange, water vapor transmission, and bacteria isolation [
101
], sericin films crosslinked
with glutaraldehyde and composite films of sericin/collagen were fabricated. These films
aim to facilitate wound healing by promoting the attachment and growth of diverse cell
types [
69
,
71
]. Also, to impart antibacterial properties to the dressing materials, nanopar-
ticles with antibacterial properties were incorporated into sericin-based
films [102–105]
.
Embarking on the elucidation of diverse sericin-based hydrogels for wound healing appli-
cations, it is essential to note that sericin hydrogel was utilized as an in situ wound healing
system demonstrating the potential to regenerate the skin both
in vitro
and
in vivo
. The
hydrogel exhibited non-toxic properties toward L929 fibroblast cells and facilitated cell
adhesion, colonization, and proliferation. In diabetic mice, wounds treated with hydrogel
for 21 days displayed decreased granulation tissue and inflammatory cells, as well as a
reduction in wound size compared to those treated with a conventional clinic-used dressing.
Another study [
64
] developed hydrogels combining sericin, chitosan, and glycosaminogly-
cans, supplemented with growth factors to enhance cellular functions and facilitate skin
tissue repair.
In vivo
studies demonstrated the hydrogels’ biocompatibility and effective-
ness in promoting skin tissue repair and angiogenesis, with minimal immune response.
These hydrogels mimic natural skin tissue properties and provide a conducive environment
for skin regeneration. Incorporating antibiotics and other antimicrobial agents into the
hydrogels amplifies their antibacterial and antifungal capabilities, addressing the common
issue of wound infection during the healing process. Hence, antimicrobial components
such as nano-silver particles [
65
,
106
], tetracycline [
107
], and zinc oxide nanoparticles [
108
]
are commonly incorporated into wound dressings based on silk sericin. For instance, in
a 2023 study [
106
], silver ion (Ag+)-modified chitosan (CS) nanoparticles were used to
deliver lupeol (L), resulting in the formation of CS-Ag-L-NPs. These nanoparticles were
enclosed within a thermosensitive self-assembling sericin hydrogel, offering several advan-
tageous outcomes. These included restraining bacterial proliferation on wound surfaces,
accelerating re-epithelialization to enhance wound closure, mitigating inflammation, and
fostering the deposition of collagen fibers. Utilizing a rat model with infected wounds, it
was observed that sericin hydrogels incorporating CS-Ag-L-NPs continuously released

J. Funct. Biomater. 2024,15, 322 20 of 36
lupeol
in vivo
, showcasing antimicrobial properties and facilitating wound recovery. More-
over, the development of an oriented SS microneedle through a template method illustrates
how rationally designed material formulations can aid in expediting wound healing. In this
approach [
108
], the central needles are relatively shorter in length compared to the edge nee-
dles, and this unique structural design facilitates wound closure by contracting the wound
edges, thereby physically promoting the healing process. Biomaterial scaffolds are sought
to create an instructive environment conducive to cell recruitment and proliferation, thereby
expediting healing cascades [
109
]. Sericin is used in scaffold fabrication through techniques
such as foam processing, solvent casting, or freeze-drying techniques. Additionally, a
3D-printed hydrogel scaffold was developed [
62
] consisting of sericin and methacrylic
anhydride-modified gelatin (GelMA) through 3D printing. Their findings showed its
ability for skin wound regeneration, with emphasis on the transparency of the hydrogel,
facilitating wound visualization. Years later, another research [
75
] explored a natural dual
protein-based nanofibrous scaffold derived from B. mori silkworm cocoons, containing
silk fibroin and sericin, for wound healing. The scaffold, featuring three layers—a silk
fibroin–PVA blend, a sericin layer containing silver(I) sulfadiazine, and a silk fibroin–PCL
blend—exhibited notable properties including excellent wettability, controlled drug release,
antibacterial, and antioxidant effects.
In vivo
experiments on male Balb/c mice demon-
strated complete wound healing and new tissue formation, indicating its potential as a
promising wound dressing material with antibacterial and antioxidant properties.
Table 7. Recent studies investigating sericin’s role in wound healing processes.
Materials Form Refs.
Fibroin, Sericin, Silver Nanoparticles and Gentamicin Films [110]
Silkworms, Sericin Scaffold [111]
Polyvinyl alcohol, Sericin, Azithromycin, Genipin Hydrogel [66]
Sericin, Chitosan, Silver Nanoparticles Films [112]
Sericin, Human Placenta-derived Extracellular Matrix Scaffold [113]
Gellan gum, Sericin, Halloysite nanotubes encapsulated with Polydopamine Hydrogel [114]
Carboxymethyl Chitosan, Sericin–Silver nanoparticles, Halloysite Sponge [115]
Sericin, Polyvinyl alcohol, Moringa oleifera leaves extract Hydrogel [116]
Sericin, Jasminum grandiflorum L. leaves extract Cream [103]
Sericin, heparin, basic fibroblast growth factor (bFGF) Hydrogel [117]
Sericin presents inherent osteogenic stimulation potential, rendering sericin-derived
biomaterials advantageous for bone repair applications. This was confirmed in a study
conducted in 2022 [
102
], where sericin extract enhanced osteoblast cell proliferation and
showed antibacterial activity against Staphylococcus aureus, reducing biofilm formation
by up to 95%. Sericin with normal saline exhibited higher stability and smaller particle
size. To regenerate bone tissue effectively, blending sericin with hydroxyapatite or other
calcium phosphate-based materials is common practice, as it mimics both the organic and
inorganic components of bone matrices. Calcium phosphate (CaP) is a substance widely
utilized for bone grafting and offers chemical stability, biocompatibility, low density, and
crystallinity [
118
]. Various studies have explored composite materials combining calcium
phosphate with proteins, synthetic polymers, or natural polymers to emulate bone tissue
quality. While synthetic polymers may lead to local reactions due to monomer release
during polymer degradation, natural polymers can yield diverse products due to differ-
ences in raw material characteristics [
119
]. In this regard, sericin/CaP emerges as a crucial
component, offering nontoxicity, mechanical stability, and a structured self-assembly capa-
bility, as sericin facilitates osteoblast migration, attachment, and proliferation, supporting
bone formation. This approach addresses sericin’s inherent mechanical limitations, en-
suring scaffolds with suitable mechanical properties for bone regeneration [
120
,
121
]. The
sericin/CaP composite exhibits potential for antitumor therapy due to its efficient loading
and release abilities [
122
]. These composites possess a notable surface area-to-volume ratio,

J. Funct. Biomater. 2024,15, 322 21 of 36
facilitating biomolecule loading and cellular membrane permeability [
123
]. Recently, a
study [
124
] aimed to enhance periodontal bone regeneration by developing a guided tissue
regeneration (GTR) membrane incorporating sericin–hydroxyapatite (Ser-HAP) composite
nanomaterials, which demonstrated potential for periodontal regeneration therapy by pro-
moting osteogenic differentiation of human periodontal membrane stem cells (hPDLSCs).
Besides hydroxyapatite, sericin can be combined with alternative biomaterials to enhance
its therapeutic efficacy, including growth factors [
125
] and functionalized agents such as
graphene oxide [
104
]. In relation to that, one of the studies [
126
] introduced a photo-
crosslinked sericin methacryloyl (SerMA)/graphene oxide (GO) hydrogel (SMH/GO) for
bone repair. The incorporation of graphene oxide substantially enhanced the compres-
sive strength of a sericin hydrogel formed through photo-polymerization, owing to its
osteoinductive and mechanical characteristics. A year later, an injectable hydrogel for
bone regeneration, comprising alginate, sericin, and graphene oxide, was developed [
104
].
Synergistically, graphene oxide enhanced cell spreading and stimulated the osteogenic
differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) by increasing
the expression of genes associated with osteogenesis cells. Both the sericin hydrogel and
sericin–alginate composite hydrogel significantly enhanced bone regeneration in rat calvar-
ial and femur defect models, respectively. The sericin hydrogel facilitated BMSC migration
and osteogenic differentiation by activating mitogen-activated protein kinases, tumor
necrosis factor (TNF), and chemokine signaling pathways for bone regeneration [
126
]. On
the other hand, the sericin–alginate composite hydrogel indirectly influenced osteogenic
differentiation by promoting M2 macrophage polarization. This effect was facilitated
by sericin, which activated signaling pathways leading to M2 macrophage polarization
and subsequent osteogenic differentiation [
104
]. Additionally,
in vivo
experiments have
shown that sericin can enhance alkaline phosphatase activity, an enzyme crucial for bone
tissue mineralization [
105
]. Functionalized with collagen–fibrin scaffolds, silk sericin ac-
celerated mineralization, enhancing osteoblastic differentiation and matrix mineralization,
demonstrated by alkaline phosphatase activity measurements [
127
]. These hybrid gel
scaffolds, created through automated gel aspiration ejections, can be customized for spe-
cific properties, serving as a model to study cell-matrix interactions for bioengineering
purposes. In addition to applications in repairing and regenerating tissues, sericin-based
biomaterials have been utilized to enhance hemostasis [
128
] and tissue adhesion [
129
,
130
].
Furthermore, they demonstrate effectiveness in treating oxidative stress and inflammatory
diseases [
129
–
132
]. For nerve tissue engineering, sericin-based hydrogels and scaffolds
have shown promise in repairing peripheral nerve injuries [
133
–
137
] and treating ischemic
stroke [
90
,
131
,
132
]. A nerve guidance conduit (NGC) is typically designed as a hollow
tubular structure made from natural or synthetic materials, providing an alternative to
grafted nerve tissue for the repair of peripheral nerve injuries [
133
]. Owing to its excellent
biocompatibility and biodegradability, sericin has been utilized for peripheral nerve repair
in combination with silicone [
134
]. This sericin/silicone conduit effectively facilitated the
restoration of nerve structure and function while repairing a 5 mm gap defect in a sciatic
nerve transection model. To enhance repair efficiency, a sericin nerve conduit loaded with
clobetasol, a glucocorticoid receptor agonist, was used to treat a 10 mm nerve defect. The
clobetasol-loaded conduit effectively repaired the defect in rats by promoting neurotrophic
factor secretion and upregulating myelin-related genes in Schwann cells [
135
]. Moreover,
it was revealed that the degraded components of a genipin-crosslinked sericin hydrogel
could facilitate axon extension and branching, as well as protect neurons from hypoxia-
induced cellular death [
131
]. Combining sericin with nerve-stimulating molecules like
nerve growth factor [
136
] and carbon nanotubes [
132
] has resulted in synergistic effects.
Furthermore, sericin-based biomaterials have proven effective in repairing injuries to skele-
tal muscle [
137
], addressing ischemic myocardial infarction [
138
], and facilitating recovery
from uterine damage [
139
,
140
]. These diverse applications underscore the potential of
sericin as both a therapeutic agent and a biomaterial.

J. Funct. Biomater. 2024,15, 322 22 of 36
6.3. Other Applications
The utilization of sericin as a supplement in culture media was initially reported
in 2002 [
141
]. It has been demonstrated that sericin emerges as a promising substitute
for bovine serum albumin (BSA), traditionally used to enhance serum-free cell culture
media. Sericin boosted cell proliferation across different mammalian cell lines, including
hybridoma 2E3-O, human hepatoblastoma (HepG2), human epithelial (HeLa), and human
embryonal kidney (293) cells, showing similar effectiveness to BSA and even enhanced
proliferation when combined with it [
141
]. Additionally, it showed the ability to enhance
the proliferation of human skin fibroblast cells, including Balb3T3 cells and RC4 corneal
cells [
142
]. Unlike BSA, sericin retained its activity after autoclaving, suggesting it could
be a safer alternative for stimulating cell growth [
141
]. Moreover, insect-derived sericin
offers potential advantages over animal-derived supplements like BSA due to its safety
profile [
141
]. Therefore, sericin presents distinct advantages—it is animal-free, sustain-
ably sourced, and biocompatible. Two recent studies investigated the effect of sericin
supplementation on bovine oocyte nuclear maturation [
143
,
144
], with one study [
143
] also
assessing DNA fragmentation. Both studies concluded that supplementation of 0.1% sericin
enhanced nuclear maturation, and one study [
143
] further noted improvements in oocyte
nuclear status while maintaining DNA integrity. In contrast to previous studies on bovine
oocytes, research by Tial et al. [
145
] aimed to boost the developmental potential of prepu-
bertal lamb oocytes for juvenile
in vitro
embryo transfer (JIVET). By supplementing the
in vitro
maturation (IVM) medium with antioxidants and cytokines, including 0.5% sericin,
significant improvements in blastocyst rates were observed. Furthermore, the addition
of fibroblast growth factor 2 (FGF2)-leukemia inhibitory factor (LIF)-insulin-like growth
factor1 (IGF1) (FLI) significantly enhanced blastocyst development. Notably, the devel-
opmental competence achieved with sericin and FLI rivaled that of adult follicular fluid,
suggesting promising avenues for improving JIVET outcomes. Another study in 2022 [
141
]
assessed whether sericin could enhance flavivirus amplification in cell cultures, particu-
larly Zika virus (ZIKV). The results showed that adding sericin at 80
µ
g/mL significantly
boosted ZIKV production in both insect (C6/36) and mammalian (Vero) cell lines, increas-
ing infectious particle concentrations by 1 log. Sericin also demonstrated cryoprotective
properties for C6/36 cells. Turning attention to human spermatozoa, the influence of
sericin supplementation on human sperm cryopreservation was investigated [
146
]. Re-
sults demonstrated that adding sericin to both freezing and thawing media significantly
improved sperm viability, and motility, and reduced DNA fragmentation, suggesting its
potential as a cryoprotective supplement for human sperm cryopreservation. Several recent
studies explored the effects of sericin supplementation on different biological systems,
promoting viability, maturation, and pigmentation of human fetal and adult retinal pig-
ment epithelial cells [
147
], enhancing
in vitro
maturation rates of mouse embryos [
148
],
and improving post-thawed quality of boar semen [
149
]. Metabolic dysfunctions such as
diabetes and hypercholesterolemia are associated with chronic inflammation, necessitating
effective treatments with minimal side effects [
150
]. There is an increasing demand for safer
antidiabetic agents due to the limitations of current therapies [
151
]. Emerging evidence
underscores the hypoglycemic [
152
–
154
] and hypocholesterolemic properties [
155
–
158
]
of sericin. Regarding anti-diabetes, one of the studies [
154
] evaluated the hypoglycemic
effects of orally administered sericin protein in type 2 diabetic mice. The results showed
reductions in blood glucose levels, improved insulin sensitivity, and enhanced antioxidative
activity, indicating sericin’s potential in managing diabetes and inflammation. Two years
later, another study [
152
] investigated the impact of degraded sericin on liver injury in type
2 diabetic rats. Dietary supplementation with sericin improved liver health and reduced
inflammation, suggesting its potential as a functional food for managing blood sugar levels.
Additionally, sericin can potentially activate the insulin–phosphoinositide 3-kinase/protein
kinase B (insulin-PI3K/AKT) signaling pathway, promoting glycogen synthesis, accelerated
glycolysis, and inhibited gluconeogenesis [
152
,
159
]. As oxidative stress is implicated in
hypercholesterolemia, sericin, known for its antioxidative properties, has been shown to

J. Funct. Biomater. 2024,15, 322 23 of 36
reduce serum cholesterol levels in various rat models, mitigating lipid peroxidation and
decreasing the absorption of dietary cholesterol in the intestines [
155
]. Mitochondria play a
significant role in ROS production, and the investigation into the effects of sericin adminis-
tration on mitochondrial architecture integrity showed a decrease in ROS production in
hepatic mitochondria [
160
]. Additionally, sericin was found to upregulate the expression of
two antioxidative proteins in hepatic mitochondria through proteomic analysis [
157
]. A re-
cent study [
157
] using hypercholesterolaemic rats examined the effects of sericin treatment
on cardiac mitochondrial structure and protein expression. The results showed that sericin
treatment led to improvements in mitochondrial structure and metabolism and alterations
in the expression of key mitochondrial proteins associated with energy production and
apoptosis regulation. Therefore, sericin is suggested as a potential treatment for cardiac
mitochondrial abnormalities under hypercholesterolaemic conditions.
6.4. Challenges and Limitations
Despite its numerous benefits and potential applications, silk sericin faces several
limitations that restrict its use in biomedical fields. A key factor is the choice of extraction
method, which plays a crucial role in maintaining a consistent physicochemical profile and
optimizing biological performance. This method must also be sustainable and scalable
for industrial applications, all while preserving the economic viability of the silk industry.
Furthermore, the extraction process can significantly influence sericin’s bioactivity [
161
].
The complexity of sericin, derived from multiple ser genes, further complicates our un-
derstanding of its biological activity mechanisms [
162
]. The limited bioactivity of silk
sericin hinders its ability to promote key functions like cellular adhesion and proliferation,
which are essential for tissue engineering. To overcome this, sericin often requires the
incorporation of bioactive molecules or other polymers to enhance its biological function-
ality. Addressing these challenges is critical to expanding sericin’s applications in drug
delivery, wound healing, and tissue scaffolding. While the current research is promising,
several key areas remain unexplored. For instance, more studies are needed to clarify how
sericin supports bone cell proliferation and healing, evaluate its long-term biocompatibility
in humans, assess the risks of allergic reactions or immune responses, and optimize its
integration into graft materials. In addition, nano-formulations of sericin have garnered
increasing attention for tissue engineering, drug delivery, and pharmaceutical applications.
However, more
in vivo
research and clinical trials are still required to fully explore the
potential of sericin-based nanocomposites in biomedicine. The underlying molecular mech-
anisms of sericin’s effects also remain unclear, requiring further investigation into cellular
interactions to enhance its therapeutic properties through integration with other bioac-
tive agents. This can be achieved through a combination of
in vitro
and
in vivo
studies,
molecular docking analyses, pharmacokinetics, and proteomic investigations. Moreover,
sericin’s high solubility in water and its animal-derived origin can limit its application in
specific biomedical areas, especially those prioritizing synthetic or plant-based materials
due to concerns about biocompatibility and ethical sourcing [
163
]. Lastly, sericin’s poor
rheological and mechanical properties, including low mechanical strength and elasticity,
prevent it from functioning independently as drug delivery systems or scaffolds for tissue
engineering. These limitations make it unsuitable for applications that require structural
support, such as bone or cartilage regeneration. As a result, sericin-based scaffolds typically
need to be combined with other materials to enhance their mechanical properties and
overall performance [164].
7. Industrial and Commercial Applications
7.1. Textile Industry Impact
Sericin, an incidental product of silk production, emerges during the degumming
process when water-containing sericin is released following the extraction of fibroin fibers.
Unfortunately, this discharge poses environmental concerns due to the substantial oxygen
demand during sericin’s bacterial degradation [
165
]. Consequently, optimizing sericin

J. Funct. Biomater. 2024,15, 322 24 of 36
utilization offers a twofold advantage: addressing textile industry waste while capitalizing
on its inherent biocompatibility, antibacterial, antimicrobial, and wound-healing properties
for textile applications [
165
]. When applied to fiber surfaces, sericin exhibits numerous
advantages. It has been observed to enhance electrical resistance, water retention, wa-
ter absorption, antibacterial capabilities, and reduce skin irritation. In conjunction with
polyester, sericin proves effective in diminishing hydrophobicity, enhancing UV protection,
and improving radical scavenging behavior [
166
]. Belhaj Khalifa et al. studied the effects
of applying sericin to wool and cotton fabrics. The results indicated that sericin does not
have an affinity toward cotton but does toward wool. Indeed, sericin improved the feel
of wool fabrics, along with their absorption capacity. They concluded that sericin could
serve as an alternative finishing agent to the toxic ones currently used in the industry.
However, the challenge they faced was the short exhaustion rate, and they suggested
grafting and crosslinking as alternatives for this treatment [
167
]. Bhandari et al. optimized
the sericin treatment conditions for the dyeability of cotton and concluded that treating
cotton with 0.5% sericin, 4% citric acid, and 1% sodium hypophosphite, followed by drying
at 70
◦
C for 4 min and curing at 160
◦
C for 2 min, was the optimal approach for enhanc-
ing dye absorption and color strength. Additionally, they proposed using sericin as an
alternative to metallic mordants in dyeing cotton fabrics to reduce water pollution and
impart functional properties like antimicrobial and ultraviolet protection properties [
168
].
A novel eco-friendly reactive dyeing method, employing sericin pre-treatment of cotton
fabric, demonstrated a significant reduction in sodium chloride (NaCl) consumption. This
approach, validated by Fourier Transform Infrared Spectroscopy (FT-IR) analysis con-
firming sericin application without crosslinking, yielded comparable color yields and
superior washing and rubbing fastnesses, while enhancing crease recovery angles, suggest-
ing sericin’s potential as a pre-dyeing agent to mitigate environmental impact in textile
coloring processes [
169
]. Another study demonstrated that sericin-coated fabric exhibited
improved wicking and moisture regain properties, rendering it suitable for direct contact
with the dermal layer, particularly for patients with skin diseases. The treated fabric showed
enhancements in antistatic, ROS scavenging, and UV absorption attributes, suggesting
potential applications in skin moisturizing, cell healing, and anti-aging [
170
]. In a study
investigating the application of Sericin/
β
-cyclodextrin in skincare textiles, treated cotton
samples exhibited excellent scavenging activity and enhanced stiffness, indicating potential
applications in cosmetotextiles for sustained skincare benefits post-washes [
171
]. Sericin
plays a crucial role in enhancing the flame retardancy of silk fibers, particularly when
combined with metal ions. Research shows that silk fabrics treated with metal ions produce
less smoke, have a higher limiting oxygen index (LOI), and form more char, indicating
improved fire resistance and wash durability. Sericin not only promotes char formation but
also works effectively with metal ions, underscoring its importance in boosting the flame
retardancy of silk fabrics, making them more suitable for applications requiring fire safety
and long-lasting performance [172].
7.2. Food Packaging and Nutraceuticals
The food industry has increasingly turned its attention to packaging solutions, seek-
ing alternatives that address concerns surrounding current packaging methods [
173
]. A
pivotal focus of research lies in identifying a novel coating that is not only cost-effective
but also edible, effectively shielding food products from the deleterious effects of oxygen,
carbon dioxide, and moisture ingress [
174
]. Such a coating would serve as a formidable
barrier against oxidation, moisture loss, and respiration, thereby extending the shelf life
of packaged goods [
174
]. Sericin, distinguished by its exceptional biocompatibility and
biodegradability, presents a promising candidate for functionalizing food packaging ma-
terials [
175
]. Despite its advantageous properties, sericin is abundantly discarded as a
by-product within the silk industry [
166
]. Therefore, leveraging sericin within the realm
of food packaging offers a twofold advantage, mitigating waste while concurrently en-
hancing packaging performance and sustainability within the food sector [
166
]. Indeed,

J. Funct. Biomater. 2024,15, 322 25 of 36
the global population is increasing constantly and is expected to reach 9.7 billion people
by 2050 [
176
]. This growth imposes greater demands on food production, necessitating
increased water, land, and energy resources [
177
]. Meanwhile, nearly 30% of food is wasted,
highlighting the urgency to extend the shelf-life of food products as a viable solution to
mitigate such waste [
178
]. The current coatings, primarily composed of synthetic poly-
mers, significantly contribute to environmental pollution due to their non-biodegradable
nature [
173
]. Natural biopolymers emerge as ideal alternatives [
179
], with protein-based
materials offering biodegradability, renewability, and non-toxicity [
180
]. Among these
alternatives, sericin demonstrates considerable potential for enhancing food quality and ex-
tending shelf life [
181
]. However, utilizing sericin for food packaging encounters challenges
such as weak mechanical properties and hydrophilicity [
182
], which can be addressed by
combining sericin with other materials to improve its properties [
183
]. Several studies have
highlighted the promising role of sericin-based edible coatings in extending the storage life
of fruits and vegetables. More importantly, the FDA has approved sericin and its derivative
as a safe material not causing allergies when taken orally and as having no cytotoxicity
effects as an ingredient in cosmetics [
184
]. Since sericin on its own cannot serve as an
effective film for food packaging due to the associated limitations [
182
], several studies
have been performed, highlighting the importance of adding other materials to sericin to
ameliorate its properties and make it a suitable candidate for food packaging, as shown
in Table 8. To tackle the challenges associated with utilizing sericin as a component of
an edible film for food packaging, several studies have been conducted. One primary
issue is the weak mechanical properties of sericin, which promote self-aggregation, thus
limiting its effectiveness as a packaging material. To address this, nanocellulose, such as
bamboo-derived cellulose nanofibrils, can be incorporated to strengthen sericin films [
183
].
Additionally, combining sericin with other biopolymers can minimize film permeability,
enhancing flexibility while reducing the need for plasticizers [
8
]. Furthermore, chemical
crosslinking reactions between sericin and glucose offer a solution to overcome limitations
in water resistance and mechanical properties [
185
]. Secondly, sericin’s hydrophilicity ren-
ders it delicate in water environments, affecting its performance. However, incorporating
sericin hydrolysate into films can increase water vapor permeability, providing a potential
solution [
186
]. Moreover, sericin films combined with glucomannan and glycerol exhibit im-
proved solubility and flexibility without compromising vapor permeability [
8
]. Moreover,
in terms of preservation, sericin-based edible coatings, containing ingredients like chitosan,
aloe vera, and glycerol, show promise in extending the storage life of perishable foods like
tomatoes [
181
]. Additionally, applying glucose to create a sericin coating helps control
food oxidation, thereby extending shelf life [
185
]. These innovative solutions demonstrate
the potential of sericin-based materials in addressing key challenges in food packaging,
paving the way for sustainable and effective packaging solutions in the industry. Dietary
sericin is a sericin protein used as a food ingredient, which has shown exciting potential
for improving food products, especially when combined with whey protein. Research
indicates that a mere 0.1% addition of sericin to whey protein significantly enhances its
mechanical strength, attributed to the formation of hydrogen bonds between the two com-
ponents [
182
]. Furthermore, dietary sericin has been effective in reducing serum cholesterol
and triglyceride levels, particularly by lowering very low-density lipoprotein (VLDL) levels
while maintaining high-density lipoprotein (HDL) levels, potentially reducing the risk
of atherosclerosis [
187
]. Moreover, a patent (Patent No. CN103918853A) describes the
application of sericin peptides as an ingredient in the formulation of low-sugar probiotic
dextrose candy, specifically designed for individuals with diabetes. Additionally, Mei
et al. developed edible bio-nanocomposite films utilizing sericin-derived carbon dots (CDs)
and chitosan, providing a multifunctional solution for food preservation. These films
exhibit various properties, including anti-counterfeiting, antibacterial, antioxidant, and
UV shielding capabilities, highlighting their potential for environmentally friendly food
packaging applications [188].

J. Funct. Biomater. 2024,15, 322 26 of 36
Table 8. Biomaterials used with sericin, the respective experimental methods for the preparation, and
the resulting added benefits on the properties of sericin.
Biomaterial Experimental Method Added Benefit References
Glucose Crosslinking Overcome limitations in water resistance.
Improve mechanical properties. [185]
Glucomannan Casting Improve solubility and flexibility. [189]
Glucomannan and glycerol Casting Improve solubility and flexibility.
Increase water vapor permeability. [189]
Chitosan and aloe vera Casting Edible food packaging films. [181]
Bacterial cellulose Solution impregnation Improve water intake. [190]
Nano-cellulose Casting Improve the mechanical properties. [183]
Glycerol Casting Enhancement of elongation properties and
increase in moisture content. [191]
ZnONPs and AgNPs on
sericin-agarose films aCasting Improve water absorption.
Enhance mechanical properties. [192]
aZnONPs: zinc oxide nanoparticules. AgNPs: silver nanoparticules.
7.3. Cosmetics and Skincare Products
Silk-based cosmetics trace their origins back to the 1960s with the production of silk
cream, initially incorporating fibroin, but recent focus has shifted toward leveraging the
beneficial properties of sericin. Sheng et al. reported that sericin shares properties akin
to collagen, a common ingredient in skincare products, known for its resemblance to
animal glue, as collagen serves as a primary raw material in skincare cosmetics [
193
].
Sericin demonstrates exceptional efficacy in moisturizing and whitening [
193
]. According
to the results of their study, sericin exhibited high moisturizing effectiveness because its
amino-acid composition is closely similar to that of the natural moisturizing factor (NMF),
which is contained in the stratum corneum that retains water and makes the skin plump
and elastic. Also, they reported that many polar groups of sericin’s polypeptide chains
were on the surface, containing almost the same amount of serine in its chain as the NMF,
29.34% and 30%, respectively [
193
]. A comparative analysis of moisture absorption showed
that a solution containing just 3% sericin achieved the same level of hygroscopicity as
a solution with 60% glycerol. This means that sericin can retain moisture effectively at
much lower concentrations compared to glycerol. Unlike glycerol, whose excessive use
can clog pores and cause irritation due to its molecular weight, sericin’s lower molecular
weight allows for easier skin absorption, aiding in reducing localized fine wrinkles [
193
].
Furthermore, significant absorption of sericin by hair was observed, enhancing hair elastic-
ity and strength [
193
]. Additionally, a 1% sericin concentration reduced tyrosine activity
by over half, thereby inhibiting melanin production and promoting skin whitening [
193
].
Singh et al. synthesized sericin/
β
-Cyclodextrin material for skin care finishing on cotton
fabric, highlighting promising attributes including antioxidant properties, UV resistance,
and effective moisture transmission [
194
]. Skin-lightening cosmetic products rely on the
tyrosinase inhibitors present, which limit the role of tyrosine in producing melanin, and
sericin has proven to have strong tyrosinase inhibition [
195
]. Kim et al. studied sericin
as a dietary component and concluded that adding 1% of sericin to the diet for 10 weeks
improved epidermal hydration [
196
]. A patent (Patent No. EP1632214A1) that outlines nail
cosmetics with sericin showed that a concentration ranging from 0.02% to 20% has been
shown to prevent chapping and brittleness while enhancing the natural glossiness of nails.
According to the forecast market value (2032F), the global sericin market is provisioned to
reach USD 537.6 million by the end of 2032 [
197
]. Silk sericin has been used in the develop-
ment of several cosmetic products for its wide range of benefits for the skin and the hair.
Several brands have developed cosmetic products containing sericin, taking advantage
of its natural moisturizing effect. Table 9states six examples of distinct brands utilizing
sericin to manufacture products for various applications.

J. Funct. Biomater. 2024,15, 322 27 of 36
Table 9. Sericin products from different brands.
Company Product Type Example References
Cicago (Englewood Cliffs, NJ, USA) Facial moisturizer EWG [198]
Drunk Elephant (Houston, TX, USA) Moisturizing shampoo EWG [198]
Imersa (Denver, CO, USA) Moisturizing cream Imersa [199]
Benefit (San Francisco, CA, USA) Mascara EWG [198]
Fondonatura (San Donato di Lecce, Italy) Hair smotherer Fondonatura [200]
J. And. C. (Como, Italy) Facial cream J&C [201]
8. Discussions and Future Perspectives
In a world where anthropogenic mass now exceeds the weight of all global living
biomass, it is imperative to move away from the traditional linear economy model, which
often leads to resource dispersion [202]. This is especially relevant in industries where by-
products, such as sericin, retain specific intrinsic properties. Promoting sericin in research
is vital due to its potential to address key challenges in biomedicine, materials science,
and sustainability. Sericin offers significant advantages over other biomaterials, including
excellent biocompatibility, biodegradability, and a wide range of multifunctional properties,
such as antioxidant, anti-inflammatory, and antimicrobial effects. These attributes make it
particularly valuable for various applications. Moreover, as a versatile globular protein,
sericin can be easily functionalized by chemical modifications or crosslinking with other
natural or synthetic polymers, enhancing its adaptability across different fields. This
functionalization capability distinguishes sericin from many other natural biomaterials,
making it both unique and highly versatile. Despite its numerous advantages, sericin has
certain limitations compared to other biomaterials. One significant challenge is its economic
viability; the extraction and purification processes can be complex and costly. Additionally,
sericin exhibits relatively low mechanical strength, particularly when compared to materials
like silk fibroin or synthetic polymers. This limitation restricts its use in load-bearing
applications. These factors need to be carefully considered when developing sericin-
based products, especially in fields that demand high structural integrity or cost-efficiency.
Nevertheless, sericin’s unique combination of properties and functional versatility positions
it as a highly promising biomaterial for a wide range of applications.
The petroleum-based plastic market presents an opportunity for the incorporation of
sericin and other bio-based materials, which can be modified to create new blends that
have the potential to replace synthetic plastics in the future. Currently, the mass production
of sericin, at 0.05 million tons annually [
203
], is minimal compared to traditional plastics, as
sericin is primarily used as an additive in various materials. As shown in Figure 8, sericin
can be combined with different biomaterials to produce pellets with enhanced properties,
potentially paving the way for its use in diverse fields to replace petroleum-based plastics.
Figure 9displays a representative scheme outlining future perspectives for employing
sericin, emphasizing the need for extensive research on its environmental, economic,
and life cycle impacts. This research is crucial for understanding the broader effects of
utilizing sericin across different applications. Given that approximately 400 million tons
of plastics are produced annually [
204
], capturing even 10% of that market for sericin
can bring substantial environmental and economic benefits. As the global population
continues to grow, the strain on resources will intensify, highlighting the importance of
shifting from a traditional linear economy to a sustainable circular economy. A circular
economy prioritizes reusing by-products instead of disposing of them, helping to mitigate
environmental consequences while optimizing natural resource consumption. Ultimately,
further research on sericin, along with the exploration of its wide-ranging applications,
will be crucial for advancing sustainable practices across various industries, addressing
resource depletion, and fostering innovative solutions for the future.

J. Funct. Biomater. 2024,15, 322 28 of 36
J. Funct. Biomater. 2024, 15, x FOR PEER REVIEW 29 of 38
make it particularly valuable for various applications. Moreover, as a versatile globular
protein, sericin can be easily functionalized by chemical modifications or crosslinking
with other natural or synthetic polymers, enhancing its adaptability across different fields.
This functionalization capability distinguishes sericin from many other natural biomateri-
als, making it both unique and highly versatile. Despite its numerous advantages, sericin
has certain limitations compared to other biomaterials. One significant challenge is its eco-
nomic viability; the extraction and purification processes can be complex and costly. Ad-
ditionally, sericin exhibits relatively low mechanical strength, particularly when com-
pared to materials like silk fibroin or synthetic polymers. This limitation restricts its use
in load-bearing applications. These factors need to be carefully considered when develop-
ing sericin-based products, especially in fields that demand high structural integrity or
cost-efficiency. Nevertheless, sericin’s unique combination of properties and functional
versatility positions it as a highly promising biomaterial for a wide range of applications.
The petroleum-based plastic market presents an opportunity for the incorporation of
sericin and other bio-based materials, which can be modified to create new blends that
have the potential to replace synthetic plastics in the future. Currently, the mass produc-
tion of sericin, at 0.05 million tons annually [203], is minimal compared to traditional plas-
tics, as sericin is primarily used as an additive in various materials. As shown in Figure 8,
sericin can be combined with different biomaterials to produce pellets with enhanced
properties, potentially paving the way for its use in diverse fields to replace petroleum-
based plastics. Figure 9 displays a representative scheme outlining future perspectives for
employing sericin, emphasizing the need for extensive research on its environmental, eco-
nomic, and life cycle impacts. This research is crucial for understanding the broader effects
of utilizing sericin across different applications. Given that approximately 400 million tons
of plastics are produced annually [204], capturing even 10% of that market for sericin can
bring substantial environmental and economic benefits. As the global population contin-
ues to grow, the strain on resources will intensify, highlighting the importance of shifting
from a traditional linear economy to a sustainable circular economy. A circular economy
prioritizes reusing by-products instead of disposing of them, helping to mitigate environ-
mental consequences while optimizing natural resource consumption. Ultimately, further
research on sericin, along with the exploration of its wide-ranging applications, will be
crucial for advancing sustainable practices across various industries, addressing resource
depletion, and fostering innovative solutions for the future.
Figure 9. Evaluation of sericin-infused bioplastic pellets for diverse applications; (a) Pellets produc-
tion from silk sericin with other biomaterials, namely BIO1, BIO2, and BIO3; (b) Environmental, (c)
economic, and (d) life cycle, assessments of the use of sericin-containing pellets.
Figure 9. Evaluation of sericin-infused bioplastic pellets for diverse applications; (a) Pellets produc-
tion from silk sericin with other biomaterials, namely BIO1, BIO2, and BIO3; (b) Environmental,
(c) economic, and (d) life cycle, assessments of the use of sericin-containing pellets.
Author Contributions: Conceptualization and methodology, R.A.; validation, investigation, and data
curation, R.A., I.D. and S.V.; writing—original draft preparation, R.A. and I.D.; writing—review and
editing, I.D. and S.V.; supervision, S.V.; funding acquisition, S.V. All authors have read and agreed to
the published version of the manuscript.
Funding: This study has received funding from the European Union’s Horizon Europe Research and
Innovation Program under grant agreement No. 101070167 and from the Fondazione Cariplo under
the project RITESSERE No. 2022-0529.
Conflicts of Interest: The authors declare no competing interests.
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