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Burn wounds are one of the most hazardous issues, globally. Silkworm produces a protein called sericin. Sericin assists in wound healing by facilitating the proliferation of keratinocytes and fibroblasts, while turmeric is potentially helpful in wound healing because of its antioxidant, anti-inflammatory, and anti-infectious activities. The current study aimed to investigate the synergetic and individual effects of turmeric, sericin, and their nanoparticles on burn wounds in mice. The female mice having age of 2 months (each weighing 29-30 g) were arbitrarily distributed in 7 groups. Five mice were added to each group. Burn wounds were induced in mice by using a hot metal rod. Burn wounds were evaluated histologically and morphologically. Turmeric nanoparticles substantially improved the wound contraction area as compared to the negative control group and other treatment groups. The serum level of glutathione (4.9 ± 0.1 µmol/L), catalase (6.0 ± 0.2 mmol/mL), glutathione peroxidase (183.4 ± 5.1 U/L), and superoxide dismutase (194.6 ± 5.1 U/mL) was significantly increased in the turmeric nanoparticles (TNPs) group as compared to the negative control (2.8 ± 0.1 µmol/L, 3.5 ± 0.1 mmol/mL, 87.8 ± 3.0 U/L, and 92.0 ± 4.8 U/mL respectively). The minimum levels of malondialdehyde (3.8 ± 0.2 mmol/L) were noticed in the TNPs group contrary to the negative control (7.4 ± 0.2 mmol/L). The restoration of the epidermis was also observed to be faster in the TNPs group as compared to all other treatment groups. The histopathological analysis also demonstrated the effectiveness of turmeric, sericin, and their nanoparticles. In conclusion, turmeric, sericin, and their nanoparticles are effective in improving the healing process of burn wounds, but TNPs showed the most effective results as compared to all other treatment groups., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This study aims to repurpose sericin in combating non-small lung cancer cells (A549 and H460) by combining it with dactolisib or vitamin D to reduce the dose of dactolisib and boost the anticancer effectiveness of dactolisib and vitamin D. Therefore, the binding affinities of individual and combined drugs were examined using in silico and protein-protein interaction studies, targeting NF-κB, Cyclin D1, p-AKT, and VEGF1 proteins. The findings manifested remarkable affinities for combinatorial drugs compared to individual compounds. To substantiate these findings, the combined IC 50 for each combination (sericin + dactolisib and sericin + vitamin D) were determined, reporting 31.9 and 41.8 µg/ml, respectively, against A549 cells and 47.9 and 55.3 µg/ml, respectively, against H460 cells. Furthermore, combination indices were assessed to lower the doses of each drug. Interestingly, in vitro results exhibited marked diminutions in NF-κB, Cyclin D1, p-AKT, and VEGF1 after treatment with sericin + dactolisib and sericin + vitamin D compared to control lung cancer cells and those treated with a single drug. Moreover, A549 and H460 cells treated with both combinations demonstrated augmented caspase-3 levels, implying substantial apoptotic activity. Altogether, these results accentuated the prospective implementation of sericin in combination with dactolisib and vitamin D at low doses to preclude lung cancer cell proliferation., (© 2024. The Author(s).)

Hydrogels with rapid wound-healing capabilities and antimicrobial effects are gaining significant interest in related fields. Nonetheless, developing a multifunctional hydrogel wound dressing with injectable self-assembling, self-healing, antimicrobial properties, and efficient skin wound-healing capabilities remained a formidable challenge. In this experiment, we drew inspiration from silkworm cocoons' natural formation and protective mechanisms, employing a novel physical cross-linking method to create an injectable and self-healing quaternary hydrogel successfully. The hydrogel is based on a matrix of silk fibroin/silk sericin (SF/SS), with 1,2-dimyristoyl-sn-glycero-3-phosphate sodium salt (DMPG) serving as a physical cross-linking agent to form the hydrogel network structure, and the incorporation of silver nanoparticles (AgNPs) further enhances its antimicrobial capabilities. Our biomimetic hydrogel, which replicated the chemical properties of silkworm cocoons, demonstrated excellent hydrophilicity with a water contact angle that ranged from 37 to 52°. Its tensile and compressive resistance was approximately four times greater than that of a pure SF hydrogel, and its swelling performance was about three times higher than that of a pure SF hydrogel. Furthermore, the hydrogel exhibited an impressive bacterial inhibition rate of over 98 % in bacterial growth and inhibition experiments, which provided a solid foundation for accelerating wound healing. Likewise, experiments with mice and histological analyses revealed that on day 7, the expression of TNF-α and IL-1β in the wound tissues treated with the SF/SS/AgNPs hydrogel was significantly reduced by >25 % compared to the blank control group. This reduction indicates that the hydrogel could decrease the production of inflammatory cytokines, potentially aiding in the acceleration of wound healing and mitigation of inflammation-related adverse reactions. By day 14, the wounds were healed mainly, with the wound area reduced by 17 % compared to that of the blank group. This demonstrates the significant potential of this cocoon-mimetic hydrogel in accelerating wound healing and providing wound protection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chronic wounds are characterised by an imbalance between pro and anti-inflammatory signals, which result in permanent inflammation and delayed re-epithelialization, consequently hindering wound healing. They are associated with bacterial infections, tissue hypoxia, local ischemia, reduced vascularization and MMP-9 upregulation. The global prevalence of chronic wounds has been estimated at 40 million in the adult population, with an alarming annual growth rate of 6.6%, making it an increasingly significant clinical problem. Sericin is a natural hydrophilic protein obtained from the silkworm cocoon. Due to its biocompatibility, biodegradability, non-immunogenicity and oxidation resistance, coupled with its excellent affinity for target biomolecules, it holds great potential in wound healing applications. The silk industry discards 50,000 tonnes of sericin annually, making it a readily available material. Sericin increases cell union sites and promotes cell proliferation in fibroblasts and keratinocytes, thanks to its cytoprotective and mitogenic effects. Additionally, it stimulates macrophages to release more therapeutic cytokines, thus improving vascularization. This review focuses on the biological properties of sericin that contribute towards enhanced wound healing process and its mechanism of interaction with important biological targets involved in wound healing. Emphasis is placed on diverse wound dressing products that are sericin based and the utilisation of nanotechnology to design sericin nanoparticles that aid in chronic wound management., (© 2024 The Wound Healing Society.)

Gold nanorods (GNRs) are unique nanoparticles with easily functionalized surfaces, multiple synthesis methods, photothermal conversion, and surface plasmon resonance effects. These properties make GNRs suitable for various biological applications. However, a rapid synthesis of GNRs using less toxic chemicals is needed. The photochemical method is a viable option that can synthesize GNRs quickly while using fewer chemicals. A photochemical method is reported for the synthesis of GNRs using Irgacure-2959 as a reducing agent. This method could be used to synthesize GNRs with a rod-like shape within 30 min. Additionally, GNRs were coated with sericin (GNRs-SC) to further reduce their toxicity in human dermal fibroblast adult cells. Low-level near-infrared (NIR) light was applied to enhance the photothermal therapy of both GNRs and GNRs-SC. The results showed that GNRs and GNRs-SC under low-level NIR light have enhanced antibacterial activity against Staphylococcus aureus and Escherichia coli , as well as antibiofilm activity against S. aureus . Furthermore, GNRs-SC showed good biocompatibility with antibacterial and antibiofilm activities. These results indicate that GNRs-SC are good candidates for various biological applications.

Ethnopharmacological Relevance: Boiled silkworm cocoons have been used to treat 'Xiaoke disease' (diabetes mellitus) recorded in Chinese medicine for over 800 years. In recent years, it has been found that the active substance silk sericin (SS) has therapeutic benefits in treating type 2 diabetes mellitus (T2DM). SS promotes pancreatic islet signalling, the proliferation of pancreatic islet cells, and insulin secretion. It is inferred that SS enters the bloodstream after oral administration and plays a role in the body's circulation. As a natural protein, SS needs to resist digestion by proteases in the gastrointestinal tract and cross the gastrointestinal barrier after oral administration. It is currently unclear how SS crosses the gastrointestinal barrier and whether it exerts therapeutic effects on T2DM by entering the circulation., Aim of the Study: To study how SS crosses the gastrointestinal barrier and whether it enters the body circulation to exert a therapeutic effect on T2DM., Materials and Methods: SS was extracted from silkworm cocoons using an alkaline method with sodium carbonate. The antidigestive capacity of SS was detected using SDS-PAGE gel electrophoresis experiments. The mode of uptake and translocation of orally consumed SS in vivo was analysed using the AP-side to BL-side and BL-side-AP-side translocations, apparent Permeability coefficient (Papp), and Exocytosis rates (ER). The study compared the differences between the adSS group and the adSS + EDTA group by using Ethylenediaminetetraacetic acid (EDTA) to separate the tight junctions between Caco-2 cells. The aim was to analyze whether the transport mode of oral filaggrin proteins in vivo could be absorbed by bypass transport. By administering SS through oral and intraperitoneal injection to type 2 diabetic mice, we measured its concentration in the blood, as well as blood glucose and insulin levels, to determine its effectiveness in treating diabetes and its ability to enter the body's circulation for treatment., Results: The molecular weight of SS decreased from 10k∼25 kDa to 10k∼15 kDa after in vitro simulated gastrointestinal fluid digestion, indicating its good antidigestive properties. The apparent Papp was greater than 1 × 10 -6  cm·s -1 , and the ER was between 0.5 and 1.5, indicating that adSS was well-absorbed and mainly passively transported. The Caco-2 cell model showed that the addition of EDTA promoted the transport of adSS, resulting in significantly larger Papp and ER values, indicating that adSS was absorbed by bypass transport. After oral administration of SS, the concentration of SS in the blood was lower than after intraperitoneal injection, which is 60% of intraperitoneal administration. Mice with a T2DM model who were administered SS for 5 weeks showed significant improvement in insulin resistance and glucose tolerance. Additionally, the pancreatic tissue appeared more regular. In the treatment of T2DM, injections of SS have been shown to be more effective than oral administration. Both oral and intraperitoneal injections have been partially involved in the circulation., Conclusions: SS is enzymatically cleaved by proteolytic enzymes in the gastrointestinal tract. The smaller molecules are partially absorbed into the body's circulation through passive and paracrine transport, exerting a therapeutic effect on T2DM., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024. Published by Elsevier B.V.)

Despite the significant progress in wound healing, chronic skin wounds remain a challenge for today's medicine. Due to the growing popularity of natural materials, silk protein-based dressings are gaining more attention in this field. Most studies refer to silk fibroin because sericin has been considered a waste product for years. However, sericin is also worth noting. Sericin-based dressings are mainly studied in cell cultures or animals. Sericin is the dressings' main component or can be included in more complex, advanced biomaterials. Recent studies highlight sericin's important role, noting its biocompatibility, biodegradability, and beneficial effects in skin wound healing, such as antibacterial activity, antioxidant and anti-inflammatory effects, or angiogenic properties. Developing sericin-based biomaterials is often simple, free of toxic by-products, and inexpensive, requiring no highly sophisticated apparatus. As a result, sericin-based dressings can be widely used in wound healing and have low environmental impact. However, the literature in this area is further limited. The following review collects and describes recent studies showing silk sericin's influence on skin wound healing., (© 2024 Wiley‐VCH GmbH.)

The skin has a multilayered structure, and deep-seated injuries are exposed to external microbial invasion and in vivo microenvironmental destabilization. Here, a bilayer bionic skin scaffold (Bilayer SF) was developed based on methacrylated sericin protein to mimic the skin's multilayered structure and corresponding functions. The outer layer (SF@TA), which mimics the epidermal layer, was endowed with the function of resisting external bacterial and microbial invasion using a small pore structure and bio-crosslinking with tannic acid (TA). The inner layer (SF@DA@Gel), which mimics the dermal layer, was used to promote cellular growth using a large pore structure and introducing dopamine (DA) to regulate the wound microenvironment. This Bilayer SF showed good mechanical properties and structural stability, satisfactory antioxidant and promote cell proliferation and migration abilities. In vitro studies confirmed the antimicrobial properties of the outer layer and the pro-angiogenic ability of the inner layer. In vivo animal studies demonstrated that the bilayer scaffolds promoted collagen deposition, neovascularization, and marginal hair follicle formation, which might be a promising new bionic skin scaffold., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The objective of this study was to develop a bio-nanocomposite coating (CQSC) by combining chitosan quaternary ammonium salt (CQAS) and sericin (SC) with biomass-derived carbon dots (CDs) to extend the shelf life of Chinese flowering cabbage (CFC). The effects of different concentrations of CDs (0.2, 0.4, 0.6, 0.8, and 1.0 mg/mL) on the physicochemical, structural, and functional activity of nanocomposite particles were evaluated. CQAS exhibited strong inhibitory effects against Escherichia coli and Bacillus subtilis. Moreover, the application of CQSC on CFC significantly reduced mass losses, slowed the increase in lignin content, maintained ascorbic acid and chlorophyll levels, inhibited the growth of microorganisms, and preserved the unique texture and aroma of CFC during storage at 10 °C compared with uncoated CFC. The results will contribute to the further development of CDs coatings to improve the postharvest preservation effect of fruits and vegetables., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Hydrogels based on poly(vinyl alcohol), silk sericin, and gelatin containing Camellia oleifera oil (CO)-loaded chitosan nanoparticles (CSNPs) were fabricated. The loading of CO into CSNPs was achieved by a two-step procedure, which included an oil-in-water emulsion and an ionic gelation method. SEM images of CO-loaded CSNPs illustrated the spherical shape with aggregation of the nanoparticles. The particle size and polydispersity index were 541-1089 nm and 0.39-0.65, respectively. The encapsulation efficiency and loading capacity were 3-16 % and 4-6 %, respectively. The gelatin/poly(vinyl alcohol)/sericin hydrogels were fabricated and incorporated with CO or CO-loaded CSNPs with different concentrations of CO-loaded CSNPs. All hydrogels demonstrated a porous structure. Besides, the hydrogels containing CO-loaded CSNPs showed a more controlled and sustained release profile than the hydrogels containing CO. Moreover, the hydrogels showed tyrosinase inhibition (9-13 %) and antioxidant activity (37-60 %). Finally, the hydrogels containing CO-loaded CSNPs were non-toxic to the Normal Human Dermal Fibroblasts and NCTC clone 929 cells, even at a high dosage of 50 mg/mL. As a result, these hydrogels exhibited excellent potential for use in cosmeceutical industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Silk sericin (SS) has a long history as a by-product of the textile industry. SS has emerged as a sustainable material for biomedical engineering due to its material properties including water solubility, diverse impact on biological activities including antibacterial and antioxidant properties, and ability to promote cell adhesion and proliferation. This review addresses the origin, structure, properties, extraction, and underlying functions of this protein. An overview of the growing research studies and market evolution is presented, along with highlights of the most common fabrication matrices (hydrogels, bioinks, porous and fibrous scaffolds) and tissue engineering applications. Finally, the future trends with this protein as a multifaceted toolbox for bioengineering are explored, along with the challenges with SS. Overall, the present review can serve as a foundation for the creation of innovative biomaterials utilizing SS as a fundamental building block that hold market potential.

Objective: This study investigated the effects of sericin on inflammation, oxidative stress, and lipid metabolism in female rats with experimental knee osteoarthritis (KOA), focusing on evaluating its effectiveness via the sterol regulatory protein (SREBP)-1C and SREBP-2 pathways., Methods: The rats were randomly assigned to three experimental groups: the C group (control), the KOA group (KOA control), and the sericin group (KOA + sericin). The KOA model was created by injecting monosodium iodoacetate (MIA) into the knee joint. Sericin was administered intra-articularly to rats on days 1, 7, 14, and 21 (0.8 g/kg/mL, 50 µL). After 21 days, the rats were sacrificed, and serum samples were analyzed using an ELISA to measure tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-10, SREBP-1c, SREBP-2, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), cholesterol, triglyceride, and total oxidant-antioxidant status (TOS-TAS) levels., Results: The KOA group exhibited higher serum TNF-α, IL-1β, TOS, SREBP-1C, ACC, FAS, triglyceride, SREBP-2, and cholesterol levels than the C group (P < 0.05). However, the levels of these cytokines, except cholesterol, were significantly lower in the sericin group than in the KOA group. The KOA group exhibited significantly lower serum TAS and IL-10 levels than the C group (P < 0.05). In the sericin group, there was a statistically significant increase (P < 0.05)., Conclusion: Sericin shows promising potential for reducing inflammation, oxidative stress, and lipid metabolism in experimental models of KOA in rats. However, further clinical research is necessary to validate the potential of sericin as a therapeutic agent for treating KOA. Key Points • Sericin can reduce knee osteoarthritis (KOA) symptoms in an experimental rat model. • In particular, in the serum of an experimental KOA rat model, sericin specifically reduces the levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), and increases the levels of anti-inflammatory cytokines, such as IL-10. • Sericin reduced lipid metabolism via the sterol regulatory protein (SREBP)-1C and SREBP-2 pathways and oxidative stress in the serum of the experimental KOA rat model. • The intra-articular administration of sericin has been shown to significantly reduce lipid metabolism, oxidative stress, and inflammation, as supported by biochemical analysis. These findings suggest its promising potential as an alternative treatment option for KOA., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Inspired by the timely emergence of silkworm pupae from their cocoons, silkworm chrysalis-like probiotic composites (SCPCs) are developed for the comprehensive therapy of inflammatory bowel disease (IBD), in which probiotics are enveloped as the "pupa" in a sequential layering of silk sericin (SS), tannic acid (TA), and polydopamine, akin to the protective "cocoon". Compared to unwrapped probiotics, these composites not only demonstrate exceptional resistance to the harsh gastrointestinal environment and exhibit over 200 times greater intestinal colonization but also safeguard probiotics from the damage of IBD environment while enabling probiotics sustained release. The probiotics, in synergy with SS and TA, provide a multi-crossed comprehensive therapy for IBD that simultaneously addresses various pathological features of IBD, including intestinal barrier disruption, elevated pro-inflammatory cytokines, heightened oxidative stress, and disturbances in the intestinal microbiota. SCPCs exhibit remarkable outcomes, including a 9.7-fold reduction in intestinal permeability, an 8.9-fold decrease in IL-6 levels, and a 2.9-fold reduction in TNF-α levels compared to uncoated probiotics. Furthermore, SCPCs demonstrate an impressive 92.25% reactive oxygen species clearance rate, significantly enhance the richness of beneficial intestinal probiotics, and effectively diminish the abundance of pathogenic bacteria, indicating a substantial improvement in the overall therapeutic effect of IBD., (© 2024 Wiley‐VCH GmbH.)

Objective: The current review is designed to elaborate and reveal the underlying mechanism of sericin and its conjugates of drug delivery during wounds and wound-related issues., Significance: Wound healing is a combination of different humoral, molecular, and cellular mechanisms. Various natural products exhibit potential in wound healing but among them, sericin, catches much attention of researchers due to its bio-functional properties such as being biodegradable, biocompatible, anti-oxidant, anti-bacterial, photo-protector, anti-inflammatory and moisturizing agent., Methods and Results: Sericin triggers the activity of anti-inflammatory cytokines which decrease cell adhesion and promote epithelial cell formation. Moreover, sericin enhances the anti-oxidant enzymes in the wounded area which scavenge the toxic consequences of reactive species (ROS)., Conclusions: This article highlights the mechanisms of how topical administration of sericin formulations along with 4-hexylresorcinol,\Chitosan\Ag@MOF-GO, polyvinyl alcohol (PVA), platelet lysate and UV photo cross-linked hydrogel sericin methacrylate which recruits a large number of cytokines on wounded area that stimulate fibroblasts and keratinocyte production as well as collagen deposition that led to early wound contraction. It also reviews the different sericin-based nanoparticles that play a significant role in rapid wound healing.

Wound infections may disrupt the normal wound-healing process. Large amounts of antibiotics are frequently used to prevent pathogenic infections; however, this can lead to resistance development. Biomaterials possessing antimicrobial properties have promising applications for reducing antibiotic usage and promoting wound healing. Silk sericin (SS) has been increasingly explored for skin wound healing applications owing to its excellent biocompatibility and antioxidant, antimicrobial, and ultraviolet-resistant properties. In recent years, SS-based composite biomaterials with a broader antimicrobial spectrum have been extensively investigated and demonstrated favorable efficacy in promoting wound healing. This review summarizes various antimicrobial agents, including metal nanoparticles, natural extracts, and antibiotics, that have been incorporated into SS composites for wound healing and elucidates their mechanisms of action. It has been revealed that SS-based biomaterials can achieve sustained antimicrobial activity by slow-release-loaded antimicrobial agents. The antimicrobial-loaded SS composites may promote wound healing through anti-infection, anti-inflammation, hemostasis, angiogenesis, and collagen deposition. The manufacturing methods, benefits, and limitations of antimicrobial-loaded SS materials are briefly discussed. This review aims to enhance the understanding of new advances and directions in SS-based antimicrobial composites and guide future biomedical research.

Knee osteoarthritis is a chronic joint disease mainly characterized by cartilage degeneration. The treatment is challenging due to the lack of blood vessels and nerve supplies in cartilaginous tissue, causing a prominent limitation of regenerative capacity. Hence, we investigated the cellular promotional and anti-inflammatory effects of sericin, Bombyx mori-derived protein, on three-dimensional chondrogenic ATDC5 cell models. The results revealed that a high concentration of sericin promoted chondrogenic proliferation and differentiation and enhanced matrix production through the increment of glycosaminoglycans, COL2A1, COL X, and ALP expressions. SOX-9 and COL2A1 gene expressions were notably elevated in sericin treatment. The proteomic analysis demonstrated the upregulation of phosphoglycerate mutase 1 and triosephosphate isomerase, a glycolytic enzyme member, reflecting the proliferative enhancement of sericin. The differentiation capacity of sericin was indicated by the increased expressions of procollagen12a1, collagen10a1, rab1A, periostin, galectin-1, and collagen6a3 proteins. Sericin influenced the differentiation capacity via the TGF-β signaling pathway by upregulating Smad2 and Smad3 while downregulating Smad1, BMP2, and BMP4. Importantly, sericin exhibited an anti-inflammatory effect by reducing IL-1β, TNF-α, and MMP-1 expressions and accelerating COL2A1 production in the early inflammatory stage. In conclusion, sericin demonstrates potential in promoting chondrogenic proliferation and differentiation, enhancing cartilaginous matrix synthesis through glycolysis and TGF-β signaling pathways, and exhibiting anti-inflammatory properties., (© 2024. The Author(s).)

Angiogenesis is pivotal for osteogenesis during bone regeneration. A hydrogel that promotes both angiogenesis and osteogenesis is essential in bone tissue engineering. However, creating scaffolds with the ideal balance of biodegradability, osteogenic, and angiogenic properties poses a challenge. Thymosin beta 10 (TMSB10), known for its dual role in angiogenesis and osteogenesis differentiation, faces limitations due to protein activity preservation. To tackle this issue, ZIF-8 was engineered as a carrier for TMSB10 (TMSB10@ZIF-8), and subsequently integrated into the self-assembled sericin hydrogel. The efficacy of the composite hydrogel in bone repair was assessed using a rat cranial defect model. Characterization of the nanocomposites confirmed the successful synthesis of TMSB10@ZIF-8, with a TMSB10 encapsulation efficiency of 88.21 %. The sustained release of TMSB10 from TMSB10@ZIF-8 has significantly enhanced tube formation in human umbilical vein endothelial cells (HUVECs) in vitro and promoted angiogenesis in the chicken chorioallantoic membrane (CAM) model in vivo. It has markedly improved the osteogenic differentiation ability of MC 3 T3-E1 cells in vitro. 8 weeks post-implantation, the TMSB10@ZIF-8/ Sericin hydrogel group exhibited significant bone healing (86.77 ± 8.91 %), outperforming controls. Thus, the TMSB10@ZIF-8/Sericin hydrogel, leveraging ZIF-8 for TMSB10 delivery, emerges as a promising bone regeneration scaffold with substantial clinical application potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Melatonin and sericin exhibit antioxidant properties and may be useful in topical wound healing patches by maintaining redox balance, cell integrity, and regulating the inflammatory response. In human skin, melatonin suppresses damage caused by ultraviolet radiation (UVR) which involves numerous mechanisms associated with reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and enhancing apoptosis. Sericin is a protein mainly composed of glycine, serine, aspartic acid, and threonine amino acids removed from the silkworm cocoon (particularly Bombyx mori and other species). It is of interest because of its biodegradability, anti-oxidative, and anti-bacterial properties. Sericin inhibits tyrosinase activity and promotes cell proliferation that can be supportive and useful in melanoma treatment. In recent years, wound healing patches containing sericin and melatonin individually have attracted significant attention by the scientific community. In this review, we summarize the state of innovation of such patches during 2021-2023. To date, melatonin/sericin-polymer patches for application in post-operational wound healing treatment has been only sparingly investigated and it is an imperative to consider these materials as a promising approach targeting for skin tissue engineering or regenerative dermatology.

The aim of this study was to assess the effectiveness of combining sericin with swimming exercise as a treatment for type-I collagenase-induced Achilles tendinopathy (AT) in rats, with a focus on inflammatory cytokines. An experimental AT model was established using type-I collagenase in male Sprague-Dawley rats, categorized into five groups: Group 1 (Control + Saline), Group 2 (AT), Group 3 (AT + exercise), Group 4 (AT + sericin), and Group 5 (AT + sericin + exercise). Intratendinous sericin administration (0.8 g/kg/mL) took place from days 3 to 6, coupled with 30 min daily swimming exercise sessions (5 days/week, 4 weeks). Serum samples were analyzed using ELISA for tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), and total antioxidant-oxidant status (TAS-TOS), alongside histopathological and immunohistochemical assessments of Achilles tendon samples. Elevated TNF-α and IL-1β and decreased IL-10 levels were evident in Group 2; Of these, TNF-α and IL-1β were effectively reduced and IL-10 increased across all treatment groups, particularly groups 4 and 5. Serum TAS was notably lower in Group 2 and significantly increased in Group 5 compared to Group 2. Histopathologically, Group 2 displayed severe degeneration, irregular fibers, and round cell nuclei, while Group 5 exhibited decreased degeneration and spindle-shaped fibers. The Bonar score increased in Group 2 and decreased in groups 4 and 5. Collagen type-I alpha-1 (Col1A1) expression was notably lower in Group 2 ( P  = 0.001) and significantly increased in groups 4 and 5 compared to Group 2 ( P  = 0.011 and 0.028, respectively). This study underscores the potential of sericin and swimming exercises in mitigating inflammation and oxidative stress linked to AT pathogenesis, presenting a promising combined therapeutic strategy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

Sericin derived from the white cocoon of Bombyx mori has been attracting more attention for its utilization in food, cosmetics, and biomedicine. The potential health benefits of natural carotenoids for humans have also been well-established. Some rare strains of Bombyx mori ( B. mori ) produce yellow-red cocoons, which endow a potential of natural carotenoid-containing sericin. We hypothesized that natural carotenoid-containing sericin from yellow-red cocoons would exhibit better properties compared with white cocoon sericin. To investigate the physicochemical attributes of natural carotenoid-containing sericin, we bred two silkworm strains from one common ancestor, namely XS7 and XS8, which exhibited different cocoon colors as a result of the inconsistent distribution of lutein and β-carotene. Compared with white cocoon sericin, the interaction between carotenoids and sericin molecules in carotenoid-containing sericin resulted in a unique fluorescence emission at 530, 564 nm. The incorporation of carotenoids enhanced the antibacterial effect, anti-cancer ability, cytocompatibility, and antioxidant of sericin, suggesting potential wide-ranging applications of natural carotenoid-containing sericin as a biomass material. We also found differences in fluorescence characteristics, antimicrobial effects, anti-cancer ability, and antioxidants between XS7 and XS8 sericin. Our work for the first time suggested a better application potential of natural carotenoid-containing sericin as a biomass material than frequently used white cocoon sericin.

Objective: To evaluate the efficacy of a modified sericin hydrogel scaffold loaded with dexamethasone (SMH-CD/DEX) scaffold for promoting bone defect healing by stimulating anti-inflammatory macrophage polarization., Methods: The light-curable SMH-CD/DEX scaffold was prepared using dexamethasone-loaded NH2-β-cyclodextrin (NH2-β-CD) and sericin hydrogel and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), biocompatibility assessment and drug release test. THP-1 macrophages incubated with the scaffold were examined for protein expressions of iNOS and Arg-1, mRNA expressions of IL-6, Il-10, Arg-1 and iNOS, and surface markers CD86 and CD206 using Western blotting, RT-qPCR, and flow cytometry. In a co-culture system of human periodontal ligament stem cells (HPDLSCs) and THP-1 macrophages, the osteogenic ability of the stem cells incubated with the scaffold was evaluated by detecting protein expressions of COL1A1 and Runx2 and expressions of ALP, Runx2, OCN and BMP2 mRNA, ALP staining, and alizarin red staining. In a rat model of mandibular bone defect, the osteogenic effect of the scaffold was assessed by observing bone regeneration using micro-CT and histopathological staining., Results: In THP-1 macrophages, incubation with SMH-CD/DEX scaffold significantly enhanced protein expressions of Arg-1 and mRNA expressions of IL-10 and Arg-1 and lowered iNOS protein expression and IL-6 and iNOS mRNA expressions. In the co-culture system, SMH-CD/DEX effectively increased the protein expressions of COL1A1 and Runx2 and mRNA expressions of ALP and BMP2 in HPDLSCs and promoted their osteogenic differentiation. In the rat models, implantation of SMH-CD/DEX scaffold significantly promoted bone repair and bone regeneration in the bone defect., Conclusion: The SMH-CD/DEX scaffold capable of sustained dexamethasone release promotes osteogenic differentiation of stem cells and bone defect repair in rats by regulating M2 polarization.

Wound healing in diabetics is often impaired or delayed due to the presence of high reactive oxygen species and low antioxidant levels. Here, a sericin-honey semi-interpenetrating network hydrogel with excellent antioxidant activity was prepared. Besides, the sericin-honey hydrogel is transparent, injectable, sticky, highly porous, and has good swelling properties, antibacterial activity, and cell compatibility. Based on its good performance in vitro , sericin-honey hydrogel achieved effective in vivo treatment on a mouse diabetic wound model, significantly accelerating the wound healing process. Furthermore, the combined effect of feeding sericin solution played a positive role in strengthening the effect of diabetic wound repair., (© 2024 IOP Publishing Ltd.)

Sericin, a natural protein derived from Bombyx mori, is known to ameliorate liver tissue damage; however, its molecular mechanism remains unclear. Herein, we aimed to identify the possible novel targets of sericin in hepatocytes and related cellular pathways. RNA sequencing analysis indicated that a low dose of sericin resulted in 18 differentially expressed genes (DEGs) being upregulated and 68 DEGs being downregulated, while 61 DEGs were upregulated and 265 DEGs were downregulated in response to a high dose of sericin (FDR ≤ 0.05, fold change > 1.50). Functional analysis revealed that a low dose of sericin regulated pathways associated with the complement and coagulation cascade, metallothionine, and histone demethylate (HDMs), whereas a high dose of sericin was associated with pathways involved in lipid metabolism, mitogen-activated protein kinase (MAPK) signaling and autophagy. The gene network analysis highlighted twelve genes, A2M, SERPINA5, MT2A, MT1G, MT1E, ARID5B, POU2F1, APOB, TRAF6, HSPA8, FGFR1, and OGT, as novel targets of sericin. Network analysis of transcription factor activity revealed that sericin affects NFE2L2, TFAP2C, STAT1, GATA3, CREB1 and CEBPA. Additionally, the protective effects of sericin depended on the counterregulation of APOB, POU2F1, OGT, TRAF6, and HSPA5. These findings suggest that sericin exerts hepatoprotective effects through diverse pathways at different doses, providing novel potential targets for the treatment of liver diseases., (© 2024. The Author(s).)

Radiation therapy used in the treatment of cancer causes skin damage, and no method of care has been established thus far. Recently, it has become clear that sericin derived from silkworm cocoons has moisturizing and antioxidant functions. In addition, green cocoon-derived sericin, which is rich in flavonoids, may have enhanced functions. However, whether this green cocoon-derived sericin can reduce radiotherapy-induced skin damage is unclear. In the present study, we aimed at establishing care methods to reduce skin cell damage caused by X-irradiation using green cocoon-derived sericin. We investigated its effect on human keratinocytes using lactate dehydrogenase activity to indicate damage reduction. Our results showed that green cocoon-derived sericin reduced cell damage caused by X-irradiation. However, this effect was not observed when cells were treated before X-irradiation or with a sericin derived from white cocoons. In addition, green cocoon-derived sericin decreased the levels of reactive oxygen species and lipid peroxidation. Our results suggest that green cocoon sericin mitigates the damaging effect of X-irradiation on cells, hence presenting potential usefulness in reducing skin damage from radiation therapy and opening new avenues in the care of cancer patients., (© 2024. The Author(s).)

Antioxidants are free radical scavengers that increase oocyte quality and improve female fertility by suppressing oxidative stress. However, the related mechanisms remain unclear. The present study was designed to examine whether a reduction of oxidative stress from using the antioxidant sericin led to expanded cumulus cell (CC)-oocyte communication and oocyte developmental acquisition in a bovine model. We found that cumulus-oocyte complexes (COCs) matured in the presence of sericin showed a significantly increased oocyte meiotic maturation rate (P < 0.01) and accelerated subsequent blastocyst formation, as more blastocysts were found at the hatched stage (P < 0.05) compared to that in the control group. In contrast to the control group, sericin suppressed H2O2 levels in COCs, resulting in a markedly enhanced CC-oocyte gap junction communication index and number of transzonal projections, which were preserved until 18 h of oocyte maturation. These findings indicate that sericin reduces disruption of oocyte-follicular cell communication induced by oxidative stress. Sericin consistently increased intra-oocyte glutathione (GSH) levels and reduced oocyte H2O2 levels (P < 0.05), both of which were ablated when GSH synthesis was inhibited by buthionine sulfoximide (an inhibitor of GSH synthesis). Furthermore, the inhibition of GSH synthesis counteracted the positive effects of sericin on subsequent embryo developmental competence (P < 0.01). Intra-oocyte GSH levels were positively associated with blastocyst development and quality. These outcomes demonstrate new perspectives for the improvement of oocyte quality in assisted reproductive technology and may contribute to developing treatment strategies for infertility and cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The present work aimed to assess the potential effect of sericin/propolis/fluorouracil nanoformula against colorectal cancer (CRC) (the fourth most common cause of cancer-related mortalities). A novel anti-cancerous formula of the synthesized sericin/propolis nanoparticles was developed and tested both in vitro (using Caco-2 cell line) and in vivo (in experimentally induced colorectal cancer animal models). The combination index of the prepared nanoformula proved that the combination between sericin/propolis nanoparticles and 5-fluorouracil demonstrated the highest synergistic effect (0.86), with dose reduction index (DRI) of the chemotherapeutic drug reaching 1.49. The mechanism of action of the prepared nanoformula revealed that it acts through the inhibition of the PI3K/AKT/mTOR signaling pathway and consequently inhibiting cancerous cells proliferation. Treatment and prophylactic studies of both sericin and propolis showed increased TBARS (Thiobarbituric Acid Reactive Substance) formation, downregulated BCL2 (B-cell lymphoma 2) and activated BAX, Caspase 9 and Caspase 3 expression. The prepared nanoformula decreased the ROS (Reactive Oxygen Species) production in vivo owing to PI3K/AKT/mTOR pathway inhibition and FOXO-1 (Forkhead Box O1) activation that resulted in autophagy/apoptosis processes stimulation. The potent anticancer effect of the prepared nanoformula was further emphasized through the in vivo histopathological studies of experimentally induced tumors. The newly formulated sericin/propolis/fluorouracil nanoparticles exhibited clear-cut cytotoxic effects toward tumor cells with provided evidence for the prophylactic effect., (© 2024. The Author(s).)

Background: In spite of much progress in cancer, the global cancer burden is still significant and increasing. Sericin, an adhesive protein of silk cocoons, has been shown to be a potential protein in various biomedical applications, including cancer therapeutics. The present study evaluates the anticancer property of sericin from cocoons of Antheraea proylei J (SAP) against human lung cancer (A549) and cervical cancer (HeLa) cell lines. This is the first report of anti-cancer activity of the non-mulberry silkworm A. proylei J., Objective: Establish the antiproliferative potential of SAP. 2. Identify the molecular mechanism of cell death induced by SAP on two different cell lines., Aims: To investigate the anticancer activity of sericin preparation from cocoons of A. proylei ., Methods: SAP was prepared from cocoons of A. proylei J. by the process of the degumming method. Cytotoxic activity was assessed by MTT assay, and genotoxicity was assessed by comet assay. Cleavage of caspase and PARP proteins and phosphorylation of MAPK pathway members were analysed by Western blotting. Cell cycle analysis was done by flow cytometer., Results: SAP causes cytotoxicity to A549 and HeLa cell lines with the IC 50 values 3.8 and 3.9 μg/μl respectively. SAP induces apoptosis in a dose-dependent manner through caspase-3 and p38, MAPK pathways in A549 and HeLa cells. Moreover, in A549 and HeLa cells, SAP induces cell cycle arrest at the S phase in a dose-dependent manner., Conclusion: The difference in the molecular mechanisms of apoptosis induced by SAP in A549 and HeLa cell lines may be due to the difference in the genotypes of the cancer cell lines. However, further investigation is warranted. The overall results of the present study envisage the possibility of using SAP as an anti-tumorigenic agent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: This study aimed to investigate the therapeutic influence of combination therapy with sericin and melatonin on attenuating diethylnitrosamine (DEN)-instigated testicular dysfunction in mice and defining the molecular mechanisms involved in orchestrating redox signaling pathways and restoring spermatogenesis and steroidogenesis., Materials and Methods: Different groups of male Swiss albino mice were established and injected with respective drugs intraperitoneally. Semen analysis, hormonal assays, and oxidative stress biomarkers were evaluated. Additionally, melatonin and its receptors, WT1, SF-1, vimentin, Nrf2, and ANXA1 expressions were assessed. Histopathological and ultrastructural features of the testes were investigated by semithin, SEM, and TEM analyses., Key Findings: Exposure to DEN exhibited pathophysiological consequences, including a remarkable increase in lipid peroxidation associated with substantial diminutions in SOD, CAT, GPx, GSH, GSH:GSSG, and GST. Furthermore, it disrupted spermatozoa integrity, testosterone, FSH, LH, melatonin, and its receptors (MT1 and MT2) levels, implying spermatogenesis dysfunction. By contrast, treatment with sericin and melatonin significantly restored these disturbances. Interestingly, the combination therapy of sericin and melatonin noticeably augmented the Nrf2, WT1, and SF-1 expressions compared to DEN-treated mice, deciphering the amelioration perceived in antioxidant defense and spermatogenesis inside cells. Furthermore, immunohistochemical detection of ANXA1 alongside histopathological and ultrastructural analyses revealed evident maintenance of testicular structures without discernible inflammation or anomalies in mice administered with sericin and melatonin compared to the DEN-treated group., Significance: Our findings highlighted that treatment with sericin and melatonin alleviated the testicular tissues in mice from oxidative stress and dysregulated spermatogenesis and steroidogenesis engendered by DEN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study investigated the efficacy of sericin in treating experimental Achilles tendinopathy (AT) in rats via the transforming growth factor-beta (TGF-β)/mothers against decapentaplegic (Smad) pathway compared with diclofenac sodium (DS)., Method: An AT model was induced in rats using collagenase enzyme type I and divided into 5 groups: C (control), AT (diseased control), ATS (AT treated with sericin), ATN (AT treated with DS), and ATSN (AT treated with sericin and DS). Sericin injection was given on the 3 rd and 6 th days by intratendinous injection (0.8 g/kg/mL), and DS was administered for 14 days by oral gavage (1.1 mg/kg/day). Serum concentrations of total oxidant-antioxidant status (TOS-TAS), TGF-β1, decorin, Smad2, and connective tissue growth factor (CTGF) were measured. Histopathologic and immunohistochemical (IHC) studies were conducted on Achilles tendon samples., Results: The TOS, oxidative stress index (OSI), TGF-β1, Smad2, CTGF, and decorin serum concentrations were significantly higher in AT than in C and significantly lower in ATS than in AT (P<0.05). Histopathological examination revealed that irregular fibers, degeneration, and round cell nuclei were significantly elevated in AT. Spindle-shaped fibers were similar to those in C, and degeneration was reduced in ATS. TGF-β1 and Smad2/3 expression was increased, and collagen type I alpha-1 (Col1A1) expression was decreased in AT vs. C (P=0.001). In the ATS, TGF-β1 and Smad2/3 expression decreased, and Col1A1 expression increased. The Bonar score significantly increased in the AT group (P =0.001) and significantly decreased in the ATS group (P =0.027)., Conclusion: Sericin shows potential efficacy in reducing oxidative stress and modulating the TGF-β/Smad pathway in experimental AT models in rats. It may be a promising therapeutic agent for AT, warranting further clinical studies for validation. Key Points • This study revealed that sericin mitigates AT-induced damage through the TGF-β/Smad pathway in an AT rat model. • ELISA and IHC investigations corroborated the effectiveness of sericin via the pivotal TGF-β/Smad pathway in tissue repair. • Evidence indicates that sericin enhances collagen synthesis,shapes tendon fiber structure, and diminishes histopathological degeneration. • Sericin's antioxidant properties were reaffirmed in its AT treatment application., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Periodontitis is a chronic inflammation caused by dental plaque. It is characterized by the accumulation of excessive reactive oxygen species (ROS) and inflammatory mediators in the periodontal area. This affects the function of host cells, activates osteoclasts, and destroys periodontal tissue. Treatments such as local debridement or antibiotic therapy for ameliorating the overactive inflammatory microenvironment and repairing periodontal tissues are challenging. This paper reports multifunctional nanoplatforms (Se-CuSrHA@EGCG) based on sericin with ROS-scavenging, immunomodulatory, angiogenic, and osteogenic capabilities. The natural protein sericin, derived from silk cocoons, is used in water/oil emulsification and cross-linking processes to create sericin nanoparticles (Se NPs). Numerous binding sites are present on the surface of Se NPs. Ion-doped hydroxyapatite nanoparticles (Se-CuSrHA NPs) can be constructed using the force between positive and negative charges. After mineralization, an antioxidant coating is formed on the surface using polyethyleneimine (PEI)/epigallocatechin gallate (EGCG). Research conducted both in vitro and in vivo demonstrates that Se-CuSrHA@EGCG NPs can efficiently scavenge ROS, regulate macrophage polarization, increase the secretion of anti-inflammatory cytokines, and balance the immune microenvironment. In addition, Se-CuSrHA@EGCG stimulates angiogenesis, inhibits osteoclasts, and accelerates periodontal tissue repair. Therefore, this is a preferable strategy to accelerate bone regeneration in patients with periodontitis., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Excessive oxidative stress, bacterial infections, and inflammation are the primary factors impeding the healing of skin wounds. Bioactive hydrogels are commonly employed in the treatment of skin injuries. However, the limited solubility of many drugs and active agents in water significantly hampers their effectiveness in hydrogel dressings. In this research, prior to incorporation into the silk fibroin (SF) hydrogel matrix, two active agents curcumin and silver nanoparticles (Ag NPs) were decorated by silk sericin to improve their dispersibility and stability in water. The resultant SF/Ag/C hydrogels combined the biological safety and nontoxicity of SF, the antioxidant and anti-inflammatory efficacy of curcumin, and the antibacterial effect of Ag NPs. These properties effectively enhanced wound repair by reducing bacterial infections, mitigating oxidative stress, suppressing the expression of pro-inflammatory factors, and promoting angiogenesis. This study presented a straightforward approach for constructing bioactive hydrogels for the promotion of the wound healing process.

Fabrication, characterization and evaluation of the larvicidal potential of novel silk protein (sericin)-based silver nanoparticles (Se-AgNPs) were the prime motives of the designed study. Furthermore, investigation of the sericin as natural reducing or stabilizing agent was another objective behind this study. Se-AgNPs were synthesized using sonication and heat. Fabricated Se-AgNPs were characterized using particle size analyzer, UV spectrophotometry, FTIR and SEM which confirmed the fabrication of the Se-AgNPs. Size of sonication-mediated Se-AgNPs was smaller (7.49 nm) than heat-assisted Se-AgNPs (53.6 nm). Being smallest in size, sonication-assisted Se-AgNPs revealed the significantly highest (F 4,10  = 39.20, p = .00) larvicidal activity against fourth instar lab and field larvae (F 4,10  = 1864, p = .00) of dengue vector (Aedes aegypti) followed by heat-assisted Se-AgNPs and positive control (temephos). Non-significant larvicidal activity was showed by silver (without sericin) which made the temperature stability of silver, debatable. Furthermore, findings of biochemical assays (glutathione-S transferase, esterase, and acetylcholinesterase) showed the levels of resistance in field strain larvae. Aforementioned findings of the study suggests the sonication as the best method for synthesis of Se-AgNPs while the larvicidal activity is inversely proportional to the size of Se-AgNPs, i.e., smallest the size, highest the larvicidal activity. Conclusively, status of the sericin as a natural reducing/stabilizing agent has been endorsed by the findings of this study. RESEARCH HIGHLIGHTS: Incorporation of biocompatible and inexpensive sericin as a capping/reducing agent for synthesis of Se-AgNPs. A novel sonication method was used for the fabrication of Se-AgNPs which were thoroughly characterized by particle size analyzer, UV-visible spectrophotometry, SEM and FTIR. Analysis of enzymatic (GSTs, ESTs) levels in field and lab strains of Aedes aegypti larvae for evaluation of insecticides resistance., (© 2023 Wiley Periodicals LLC.)

Mesenchymal stem cells (MSCs) are excellent seed cells for cartilage tissue engineering and regenerative medicine. Though the condensation of MSCs is the first step of their differentiation into chondrocytes in skeletal development, the process is a challenge in cartilage repairing by MSCs. The pericellular matrix (PCM), a distinct region surrounding the chondrocytes, acts as an extracellular linker among cells and forms the microenvironment of chondrocytes. Inspired by this, sericin nano-gel soft-agglomerates were prepared and used as linkers to induce MSCs to assemble into micro-spheres and differentiate into cartilage-like micro-tissues without exogenous stimulation of growth factors. These sericin nano-gel soft-agglomerates are composed of sericin nano-gels prepared by the chelation of metal ions and sericin protein. The MSCs cultured on 2D culture plates self-assembled into cell-microspheres centered by sericin nano-gel agglomerates. The self-assembly progress of MSCs is superior to the traditional centrifugation to achieve MSC condensation due to its facility, friendliness to MSCs and avoidance of the side-effects of growth factors. The analysis of transcriptomic results suggested that sericin nano-gel agglomerates offered a soft mechanical stimulation to MSCs similar to that of the PCM to chondrocytes and triggered some signaling pathways as associated with MSC chondrogenesis. The strategy of utilizing biomaterials to mimic the PCM as a linker and as a mechanical micro-environment and to induce cell aggregation and trigger the differentiation of MSCs can be employed to drive 3D cellular organization and micro-tissue fabrication in vitro . These cartilage micro-masses reported in this study can be potential candidates for cartilage repairing, cellular building blocks for 3D bio-printing and a model for cartilage development and drug screening.

The effect of sericin in high glucose (HG)-induced podocyte injury and the mechanisms involving Snai1 and miR-30a-5p were investigated. Bioinformatics and dual-luciferase reporter assay evaluated the relationship of Snai1 with miR-31a-5p. Podocyte injury mouse induced by HG were randomly divided into control (5.5mmol/L D-glucose), HG (30mmol/L D-glucose), HG + Sericin (30mmol/L D-glucose+600μg/ml sericin), miR-30a-5p inhibitor NC (sericin+30mmol/L D-glucose+miR-30a-5p inhibitor negative control) and miR-30a-5p inhibitor groups (sericin+30mmol/L D-glucose+miR-30a-5p inhibitor). The migration ability of podocytes was detected by Transwell assay. The expressions of Snai1, podocin, E-cadherin, FSP-1, ZO-1, α-SMA, Desmin, and miR-30a-5p were assessed with RT-qPCR and Western blot. Snai1 was one direct target of miR-30a-5p. HG group had significantly larger number of migrated podocytes and higher levels of Snai1, FSP-1, α-SMA and Desmin, but significantly lower levels of podocin, ZO-1 and E-cadherin than control and HG + Sericin group. These effects of sericin were reversed by miR-30a-5p inhibitor, as evidenced by increased podocyte migration and increased expressions of Snai1, α-SMA, FSP-1 and Desmin, whereas decreased expressions of podocin, ZO-1 and E-cadherin. Sericin may protect podocytes from damage caused by HG via up-regulating epithelial phenotype markers, down-regulating mesenchymal phenotype markers, and reducing migration of podocytes. The mechanism may be through targeting miR-30a-5p and its target Snai1.

Thermoplastic polyurethane (TPU) membrane has super physical-mechanical properties and biocompatibility, but the surface is inert and lack of active groups which limit its application in cell culture. Silk sericin (SS) can improve cell adhesion, proliferation, growth and metabolism. In this paper, SS was grafted onto the surface of TPU membrane by -NH 2 bridge to build a high efficiency cell culture membrane. The FT-IR spectrum results indicated SS was grafted by chemical bond. According to the SEM and AFM results, we found that the grafting of SS reduced the water contact angle by 43.31% and increased the surface roughness by about four times. When TPU-SS was used for HepG2 cell culture, the cell adhesion rate of TPU-SS was significantly higher than that of the general TCPS cell culture plate, and the cell proliferation rate was close to that of TCPS. FDA/EB staining showed that HepG2 cells remained a better cellular growth behavior. HepG2 cells had higher cell vitality including the albumin secretion and the intracellular total protein synthesis. Grafting SS maintained the stability of cell and significantly decreased the cytotoxicity by decreased LDH release. In conclusion, SS grafting is beneficial to cell culture in vitro , and provides a key material for bioartificial liver culture system.

Diabetic wounds are serious complications caused by diabetes mellitus (DM), which are further exacerbated by angiogenesis disorders and prolonged inflammation. Injectable platelet-rich fibrin (i-PRF) is rich in growth factors (GFs) and has been used for the repair and regeneration of diabetic wounds; however, direct application of i-PRF has certain disadvantages, including the instability of the bioactive molecules. Sericin hydrogel, fabricated by silkworm-derived sericin, is a biocompatible material that has anti-inflammatory and healing-promoting properties. Therefore, in this study, we developed a novel hydrogel (named sericin/i-PRF hydrogel) using a simple one-step activation method. The in vitro studies showed that the rapid injectability of the sericin/i-PRF hydrogel allows it to adapt to the irregular shape of the wounds. Additionally, sericin hydrogel could prolong the release of i-PRF-derived bioactive GFs in the sericin/i-PRF hydrogel. Furthermore, sericin/i-PRF hydrogel effectively repaired diabetic wounds, promoted angiogenesis, and reduced inflammation levels in the diabetic wounds of nude mice. These results demonstrate that the sericin/i-PRF hydrogel is a promising agent for diabetic wound healing., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Limin Bai et al.)

Therapeutic treatment forms can play significant roles in resolving psoriatic plaques or promoting wound repair in psoriatic skin. Considering the biocompatibility, mechanical strength, flexibility, and adhesive properties of silk fibroin sheets/films, it is useful to combine them with anti-psoriatic agents and healing stimulants, notably silk sericin. Here, we evaluate the curative properties of sericin-coated thin polymeric films (ScF) fabricated from silk fibroin, using an imiquimod-induced psoriasis rat model. The film biocompatibility and psoriatic wound improvement capacity was assessed. A proteomics study was performed to understand the disease resolving mechanisms. Skin-implantation study exhibited the non-irritation property of ScF films, which alleviate eczema histopathology. Immunohistochemical and gene expression revealed the depletion of β-defensin, caspase-3 and -9, TNF-α, CCL-20, IL-1β, IL-17, TGF-β, and Wnt expressions and S100a14 mRNA level. The proteomics study suggested that ScF diminish keratinocyte proliferation via the mTOR pathway by downregulating mTOR protein, corresponding to the modulation of TNF-α, Wnt, and IL-1β levels, leading to the enhancement of anti-inflammatory environment by IL-17 downregulation. Hematology data demonstrated the safety of using these biomaterials, which provide a potential therapeutic-option for psoriasis treatment due to desirable effects, especially anti-proliferation and anti-inflammation, functioning via the mTOR pathway and control of IL-17 signaling., (© 2023. The Author(s).)

Lupeol, a pentacyclic triterpene, has demonstrated significant wound healing properties; however, its low water solubility has limited its clinical applicability. To overcome this limitation, we utilized Ag + -modified chitosan (CS-Ag) nanoparticles to deliver lupeol, resulting in the formation of CS-Ag-L-NPs. These nanoparticles were then encapsulated within a temperature-sensitive, self-assembled sericin hydrogel. Various analytical methods, including SEM, FTIR, XRD, HPLC, TGA assay, hemolysis and antibacterial activity tests, were employed to characterize the nanoparticles. Additionally, an infectious wound model was used to evaluate the therapeutic and antibacterial efficacy of the CS-Ag-L-NPs modified sericin hydrogel. Our results showed that the encapsulation efficiency of lupeol in CS-Ag-L-NPs reached 62.1 %, with good antibacterial activity against both gram-positive and gram-negative bacteria and a low hemolysis ratio (<5 %). The CS-Ag-L-NPs sericin gel exhibited multiple beneficial effects, including inhibiting bacterial proliferation in wound beds, promoting wound healing via accelerated re-epithelialization, reducing inflammation, and enhancing collagen fiber deposition. We conclude that the CS-Ag-L-NPs loaded sericin hydrogel has tremendous potential for development as a multifunctional therapeutic platform capable of accelerating wound healing and effectively suppressing bacterial infections in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Protein-based nanocarriers have demonstrated good potential for cancer drug delivery. Silk sericin nano-particle is arguably one of the best in this field. In this study, we developed a surface charge reversal sericin-based nanocarrier to co-deliver resveratrol and melatonin (MR-SNC) to MCF-7 breast cancer cells as combination therapy. MR-SNC was fabricated with various sericin concentrations via flash-nanoprecipitation as a simple and reproducible method without complicated equipment. The nanoparticles were subsequently characterized for their size, charge, morphology and shape by dynamic light scattering (DLS) and scanning electron microscope (SEM). Nanocarriers chemical and conformational analysis were done by fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) respectively. In vitro drug release was determined at different pH values (7.45, 6.5 and 6). The cellular uptake and cytotoxicity were studies using breast cancer MCF-7 cells. MR-SNC fabricated with the lowest sericin concentration (0.1%), showed a desirable 127 nm size, with a net negative charge at physiological pH. Sericin structure was preserved entirely in the form of nano-particles. Among the three pH values we applied, the maximum in vitro drug release was at pH 6, 6.5, and 7.4, respectively. This pH dependency showed the charge reversal property of our smart nanocarrier via changing the surface charge from negative to positive in mildly acidic pH, destructing the electrostatic interactions between sericin surface amino acids. Cell viability studies demonstrated the significant toxicity of MR-SNC in MCF-7 cells at all pH values after 48 h, suggesting a synergistic effect of combination therapy with the two antioxidants. The efficient cellular uptake of MR-SNC, DNA fragmentation and chromatin condensation was found at pH 6. Nutshell, our result indicated proficient release of the entrapped drug combination from MR-SNC in an acidic environment leading to cell apoptosis. This work introduces a smart pH-responsive nano-platform for anti-breast cancer drug delivery., (© 2023. The Author(s).)

The complications associated with diabetic wounds make their healing process prolonged. Hydrogels could be ideal wound dressings therefore present research was conducted to prepare silk sericin (an adhesive protein polymer) based hydrogels in combination with plant extracts and to evaluate its effectiveness against wound healing process in mice with alloxan induced diabetes. Excision wounds were formed via a biopsy puncture (6 mm). Experimental hydrogels were prepared and applied topically on the diabetic wounds. All the hydrogel treatment groups showed significantly higher (P < 0.001) percent wound contraction from day 3 to day 11 as compared to the negative diabetic control group. The serum level of anti-inflammatory cytokine (Interleukin-10) and tissue inhibitor metalloproteinase (TIMP) was significantly higher (P < 0.001), while the level of pro-inflammatory cytokines (tumor necrosis factor-α, Interleukin-6) and matrix metalloproteinases (MMP-2, MMP-9) was significantly lower (P < 0.001) in hydrogels treatment groups as compared to diabetic control group. Although all the hydrogels showed effective results, however the best results were shown by 4 % sericin+4 % banyan+4 % onion based hydrogel. It can be concluded that Sericin based hydrogel enriched with banyan and onion extracts can be used as an effective remedy for the treatment of diabetic wounds due to their high healing and regenerative properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Assessing the beneficial effects of silk sericin against hepatic injury induced by diethylnitrosamine (DEN)., Methods: Aiming at promoting sericin as a natural product able to counteract the hazards of toxic elements, HPLC profile was conducted on the extracted sericin sample versus the standard one to qualitatively identify it. Following sericin treatment on human HepG2 liver cancer cells, many parameters were analyzed in vitro including cell viability, cell cycle, and cell apoptosis. Hepatic pro-inflammatory cytokines as well as histopathological and ultrastructure changes were evaluated in vivo in the different experimental groups., Results: Sericin exhibited a dose-dependent cytotoxic effect on HepG2 cells with an IC50 of 14.12 + 0.75 μg/mL. The hepatotoxicity of DEN was manifested in mice by increased pro-inflammatory markers (IL-2, IL-6, and TNF-α), decreased IL-10, liver structure deterioration, and characteristic histopathological and ultrastructure changes. Sericin administration reversed most of the observed alterations inflected by DEN., Conclusions: Our results substantiate the sericin's powerful apoptotic impact in vitro. In experimental mice, combination treatment using sericin together with melatonin appears to be more potent in mitigating the adverse effects of DEN. However, further investigations are needed to identify the underlying mechanism of action and complement the knowledge about the expected medicinal values of sericin., Competing Interests: Competing interests The authors have declared no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Ovarian tissue cryopreservation is an effective fertility protective strategy for preadolescent female cancer patients, whose tumor treatment cannot be delayed. In the present study, the effects of sericin, as an antioxidant, on mice ovarian tissue freezing and thawing were investigated. Mice ovarian tissues were cryopreserved and thawed in medium containing 0.5% or 1%sericin (w/v), and 0.1 mM melatonin. Then, the follicular morphology was observed. The levels of antioxidant enzymes were determined, including glutathione (GSH), glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) and catalase (CAT). Moreover, the levels of nitric oxide (NO), malondialdehyde (MDA) and lactate dehydrogenase (LDH) were also tested. Besides, apoptosis-related proteins Bcl-2 and Bax were determined. Our results showed that 1% sericin maintained follicular morphology, inhibited apoptosis, decreased MDA and NO levels, and boosted endogenous antioxidant enzyme levels, while had no significant effect on LDH levels. Furthermore, these effects may be related with the activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of Rapamycin (mTOR) signaling pathway, as demonstrated by increased PI3K, p-AKT and mTOR levels. These findings demonstrate that 1% sericin may reduce oxidative stress and protect ovarian tissues during freezing and thawing via PI3K/AKT/mTOR signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In recent times, numerous natural materials have been used for the fabrication of gold nanoparticles (AuNPs). Natural resources used for the synthesis of AuNPs are more environment friendly than chemical resources. Sericin is a silk protein that is discarded during the degumming process for obtaining silk. The current research used sericin silk protein waste materials as the reducing agent for the manufacture of gold nanoparticles (SGNPs) by a one-pot green synthesis method. Further, the antibacterial effect and antibacterial mechanism of action, tyrosinase inhibition, and photocatalytic degradation potential of these SGNPs were evaluated. The SGNPs displayed positive antibacterial activity (8.45-9.58 mm zone of inhibition at 50 μg/disc) against all six tested foodborne pathogenic bacteria, namely, Enterococcus feacium DB01, Staphylococcus aureus ATCC 13565, Listeria monocytogenes ATCC 33090, Escherichia coli O157:H7 ATCC 23514, Aeromonas hydrophila ATCC 7966, and Pseudomonas aeruginosa ATCC 27583. The SGNPs also exhibited promising tyrosinase inhibition potential, with 32.83% inhibition at 100 μg/mL concentration as compared to 52.4% by Kojic acid, taken as a reference standard compound. The SGNPs also displayed significant photocatalytic degradation effects, with 44.87% methylene blue dye degradation after 5 h of incubation. Moreover, the antibacterial mode of action of the SGNPs was also investigated against E. coli and E. feacium , and the results show that due to the small size of the nanomaterials, they could have adhered to the surface of the bacterial pathogens, and could have released more ions and dispersed in the bacterial cell wall surrounding environment, thereby disrupting the cell membrane and ROS production, and subsequently penetrating the bacterial cells, resulting in lysis or damage to the cell by the process of structural damage to the membrane, oxidative stress, and damage to the DNA and bacterial proteins. The overall outcome of the current investigation concludes the positive effects of the obtained SGNPs and their prospective applications as a natural antibacterial agent in cosmetics, environmental, and foodstuff industries, and for the management of environmental contagion.

With the demand for more efficient and safer therapeutic drugs, targeted therapeutic peptides are well received due to their advantages of high targeting (specificity), low immunogenicity, and minimal side effects. However, the conventional methods of screening targeted therapeutic peptides in natural proteins are tedious, time-consuming, less efficient, and require too many validation experiments, which seriously restricts the innovation and clinical development of peptide drugs. In this study, we established a novel method of screening targeted therapeutic peptides in natural proteins. We also provide details for library construction, transcription assays, receptor selection, therapeutic peptide screening, and biological activity analysis of our proposed method. This method allows us to screen the therapeutic peptides TS263 and TS1000, which have the ability to specifically promote the synthesis of the extracellular matrix. We believe that this method provides a reference for screening other drugs in natural resources, including proteins, peptides, fats, nucleic acids, and small molecules.

Wound repair is challenging for traditional wound dressings. New bioactive dressings need to be developed urgently. Herein, we reported a highly bioactive silk protein wound dressing (SPD) with natural silk fiber-sericin hydrogel interpenetrating double network structure, which combines the dual characteristics of natural silk and sericin hydrogel. Silk fiber scaffolds were secreted directly from silkworms bred by regulating their spinning behaviors. Sericin in SPD is obtained by dissolving silkworm cocoons at high temperature and high pressure, while it remains intact activities to self-assemble a hydrogel. To explore the effect of SPD, we first systematically evaluated its physicochemical properties and biological activities in vitro . The SPD exhibits high porosity, prominent mechanical strength, pH-responsive degradability, and excellent anti-oxidation and cell compatibility. Besides, SPD can load and maintain long-term drug release. Based on the satisfactory performance of SPD in vitro , effective in vivo treatment was achieved in a mouse full-thickness wound model, as demonstrated by a significantly accelerated wound healing process, promote the regeneration of hair follicles and sebaceous glands, increased expression of vascular endothelial growth factor, and reduced inflammation. Further, resveratrol was loaded into SPD to enhance the effects of anti-oxidation and anti-inflammation for wound healing. Our investigation shows that SPD with excellent physicochemical and biological properties applied in a murine full-thickness skin wound model resulted in remarkable and efficient acceleration of healing process, which may inspire the design of new, effective, and safer medical materials for tissue regeneration., (© 2023 IOP Publishing Ltd.)

It is attractive and challenging to develop a bioactive dressing based on native nondestructive sericin. Here, a native sericin wound dressing was secreted directly by silkworms bred through regulating their spinning behaviors. To be excited, our first reported wound dressing possesses original unique features of natural sericin, including natural structures and bioactivities. Besides, it has a porous fibrous network structure with a porosity of 75 %, thus achieving excellent air permeability. Moreover, the wound dressing exhibits pH-responsive degradability, softness, and super absorbency properties whose equilibrium water contents are no less than 75 % in various pH conditions. Furthermore, the sericin wound dressing demonstrates high mechanical strength, reaching 2.5 MPa tensile strength. Importantly, we confirmed good cell compatibility of sericin wound dressing that can support cell viability, proliferation, and migration for a long time. When tested in a mouse full-thickness skin wound model, the wound dressing efficiently accelerated the healing process. Our findings suggest that the sericin wound dressing has promising application and commercial value in wound repair., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Silk fibroin (SF) and sericin (SS), the two major proteins of silk, are attractive biomaterials with great potential in tissue engineering and regenerative medicine. However, their biochemical interactions with stem cells remain unclear. In this study, multiomics are employed to obtain a global view of the cellular processes and pathways of mesenchymal stem cells (MSCs) triggered by SF and SS to discern cell-biomaterial interactions at an in-depth, high-throughput molecular level. Integrated RNA sequencing and proteomic analysis confirm that SF and SS initiate widespread but distinct cellular responses and potentiate the paracrine functions of MSCs that regulate extracellular matrix deposition, angiogenesis, and immunomodulation through differentially activating the integrin/PI3K/Akt and glycolysis signaling pathways. These paracrine signals of MSCs stimulated by SF and SS effectively improve skin regeneration by regulating the behavior of multiple resident cells (fibroblasts, endothelial cells, and macrophages) in the skin wound microenvironment. Compared to SS, SF exhibits better immunomodulatory effects in vitro and in vivo, indicating its greater potential as a carrier material of MSCs for skin regeneration. This study provides comprehensive and reliable insights into the cellular interactions with SF and SS, enabling the future development of silk-based therapeutics for tissue engineering and stem cell therapy., (© 2023 Wiley-VCH GmbH.)

Oxidative stress caused by environmental exposures results in numerous skin diseases. Phloretin (PHL) is often used to relieve various skin symptoms, however, precipitation or crystallization of PHL in aqueous systems limits its ability to diffuse through the stratum corneum, making it difficult to exert effect at the target. To address this challenge, we herein report a method for the generation of core-shell nanostructure (G-LSS) via the growth of sericin crust around gliadin nanoparticle as a topical nanocarrier of PHL to improve its cutaneous bioavailability. Physicochemical performance, morphology, stability, and antioxidant activity of the nanoparticles were characterized. G-LSS-PHL exhibited uniformed spherical nanostructures with the robust encapsulation on PHL (∼90 %). This strategy protected PHL from UV-induced degradation, facilitating to inhibit erythrocyte hemolysis and quench free radicals in a dose-dependent manner. Transdermal delivery experiments and porcine skin fluorescence imaging indicated that G-LSS facilitated the penetration of PHL across the epidermis layer of skin to reach deep-seated sites, and promoted cumulative turnover of PHL with a 2.0-fold increase. Cell cytotoxicity and uptake assay confirmed that as-prepared nanostructure was nontoxic to HSFs, and promoted cellular absorption of PHL. Therefore, this work opened up new promising avenues for developing robust antioxidant nanostructure for topical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The development of wound dressings with hemostatic and antibacterial properties has attracted great attention. In this study, we prepared a multi-functional natural substance sponge (CMC/Ser-Ag/HNT) composed of carboxymethyl chitosan (CMC), sericin-silver nanoparticle (Ser-Ag), and halloysite (HNT). CMC/Ser-Ag/HNT sponge was demonstrated to bear desired hygroscopicity, porosity, compressive strength and compressive stability, cytocompatibility, and hemocompatibility. The mechanical properties (compressive strength of 100 kPa) and hemostatic capacity (hemostasis time of 15 ± 3 s in the liver injury model and 12 ± 3 s in the caudal injury model) were enhanced by introducing HNT into the CMC sponge. Ser-Ag was synthesized in situ via the redox nature of tyrosine residues in sericin in a "one-step, green" way to enhance the antibacterial activity of the hybrid sponge against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In addition, the rat full-thickness skin defect model experiments demonstrated that the CMC/Ser-Ag/HNT4 sponge significantly promoted epithelialization and collagen formation. Immunofluorescence staining assays revealed that the composite sponge reduced inflammation by downregulating the expression of IL-6 and enhanced angiogenesis by upregulating VEGF expression. All the findings demonstrated the great potential of CMC/Ser-Ag/HNT sponge as versatile clinical wound dressing, especially for hemorrhagic and infected wounds., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Immune responses and osteogenesis differentiation induced by implants are crucial for bone tissue regeneration. Consideration of only one of those properties is not sufficient. To investigate the synergistic actions, we designed alginate/graphene oxide/sericin/nanohydroxyapatite (Alg/GO/Ser/nHAP) nanocomposite hydrogels with both osteoimmunomodulatory and osteoinductive activities. This study aimed to explore the effect of hydrogel with osteoimmunomodulatory properties on promoting osteogenesis of bone marrow stem cells (BMSCs)., Methods: Alg/GO/Ser/nHAP nanocomposite hydrogel was fabricated and was characterized by SEM, FTIR, XRD, stress-strain, rheology, swelling and degradation. After the impact of sericin on M2 macrophage polarization was identified, the BMSCs viability and adhesion were evaluated by CCK8 assay, live/dead staining, cytoskeleton staining. The cell osteogenic differentiation was observed by ALP/ARS staining, immunofluorescence staining, RT-PCR, and Western blotting, respectively. Rat cranial defect model was used to assess osteoimmunomodulatory effects of scaffolds in vivo by micro‑computed tomographic, histological, and immunohistochemical analyses after 8 weeks of healing., Results: In vitro experiments revealed that the hydrogel presented desirable mechanical strength, stability, porosity, and biocompatibility. Significantly, sericin and nHAP appeared to exert synergistic effects on bone regeneration. Sericin was observed to inhibit the immune response by inducing macrophage M2-type polarization to create a positive osteoimmune microenvironment, contributing to improving osseointegration at the bone-implant interface to promote osteogenesis. However, the osteogenic differentiation in rat BMSCs was further enhanced by combining nHAP and sericin in the nanocomposite hydrogel. Eventually, the hydrogel was implanted into the rat cranial defect model, assisting in the reduction of local inflammation and efficient bone regeneration., Conclusion: The nanocomposite hydrogel stimulated bone formation by the synergistic effects of immunomodulation of macrophage polarization by sericin and direct osteogenic induction by nHAP, demonstrating that such a scaffold that modulates the osteoimmune microenvironment to promote osteogenesis is a promising approach for the development of bone tissue engineering implants in the future., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Fu et al.)