Self-assembly mucoadhesive beads of κ-carrageenan/sericin for indomethacin oral extended release.

Oral drug administration, especially when composed of mucoadhesive delivery systems, has been a research trend due to increased residence time and contact with the mucosa, potentially increasing drug bioavailability and stability. In this context, this study aimed to develop self-assembly mucoadhesive beads composed of blends of κ-carrageenan and sericin (κ-Car/Ser) loaded with the anti-inflammatory drug indomethacin (IND). We investigated the swelling, adhesion behaviour, and mechanical/physical properties of the beads, assessing their effects on cell viability, safety and permeation characteristics in both 2D and triple-culture model. The swelling ratio of the beads indicated pH-responsiveness, with maximum water absorption at pH 6.8, and strong mucoadhesion, increasing primarily with higher polymer concentrations. The beads exhibited thermal stability and no chemical interaction with IND, showing improved mechanical properties. Furthermore, the beads remained stable during accelerated and long-term storage studies. The beads were found to be biocompatible, and IND encapsulation improved cell viability (>70 % in both models, 79 % in VN) and modified IND permeation through the models (6.3 % for F5 formulation (κ-Car 0.90 % w/v | Ser 1.2 % w/v| IND 3.0 g); 10.9 % for free IND, p < 0.05). Accordingly, κ-Car/Ser/IND beads were demonstrated to be a promising IND drug carrier to improve oral administration while mitigating the side effects of non-steroidal anti-inflammatories.

Thymosin beta 10 loaded ZIF-8/sericin hydrogel promoting angiogenesis and osteogenesis for bone regeneration.

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.

Effect of rheological behaviors of polyacrylonitrile grafted sericin solution on film structure and mechanical properties.

Sericin protein possesses excellent biocompatibility, antioxidation, and processability. Nevertheless, manufacturing large quantities of strong and tough pure regenerated sericin materials remains a significant challenge. Herein, we design a lightweight structural sericin film with high ductility by combining radical chain polymerization reaction and liquid-solid phase inversion method. The resulting polyacrylonitrile grafted sericin films exhibit the ability to switch between high strength and high toughness effortlessly, the maximum tensile strength and Young's modulus values are 21.92 ± 1.51 MPa and 8.14 ± 0.09 MPa, respectively, while the elongation at break and toughness reaches up to 344.10 ± 35.40 % and 10.84 ± 1.02 MJ·m-3, respectively. Our findings suggest that incorporating sericin into regenerated films contributes to the transformation of their mechanical properties through influencing the entanglement of molecular chains within polymerized solutions. Structural analyses conducted using infrared spectroscopy and X-ray diffraction confirm that sericin modulates the mechanical properties by affecting the transition of condensed matter conformation. This work presents a convenient yet effective strategy for simultaneously addressing the recycling of sericin as well as producing regenerated protein-based films that hold potential applications in biomedical, wearable, or food packaging.

Inclusion of reeling wastewater-derived sericin peptides in high-protein nutrition bars for antihardening and storage stability.

The utilization of agroindustrial wastes to enrich food protein resources and the exploration of their broader applications are crucial for addressing the food crisis and achieving sustainable development goals. In this study, reeling wastewater-derived sericin was hydrolyzed using papain and trypsin to prepare sericin peptide (SRP) and was used as an antihardening ingredient of high-protein nutrition bars (HPNBs). The mechanism of the antihardening effect of SRP was elucidated by investigating the content of advanced glycation end products and protein oxidation products (carbonyl and free sulfhydryl), and the molecular weight change of HPNBs during storage before and after the addition of SRP. Our results confirmed the fortification of HPNBs with SRP, which is beneficial for the promotion and expansion of sericin applications in the food industry, with positive implications for the rational utilization of protein resources and the enrichment of food protein sources.

DIFUCOSIN: DIclofenac sodium salt loaded FUCOidan-SericIN nanoparticles for the management of chronic inflammatory diseases.

The current investigation emphasizes the use of fucoidan and sericin as dual-role biomaterials for obtaining novel nanohybrid systems for the delivery of diclofenac sodium (DS) and the potential treatment of chronic inflammatory diseases. The innovative formulations containing 4 mg/ml of fucoidan and 3 mg/ml of sericin showed an average diameter of about 200 nm, a low polydispersity index (0.17) and a negative surface charge. The hybrid nanosystems demonstrated high stability at various pHs and temperatures, as well as in both saline and glucose solutions. The Rose Bengal assay evidenced that fucoidan is the primary modulator of relative surface hydrophobicity with a two-fold increase of this parameter when compared to sericin nanoparticles. The interaction between the drug and the nanohybrids was confirmed through FT-IR analysis. Moreover, the release profile of DS from the colloidal systems showed a prolonged and constant drug leakage over time both at pH 5 and 7. The DS-loaded nanohybrids (DIFUCOSIN) induced a significant decrease of IL-6 and IL-1ß with respect to the active compound in human chondrocytes evidencing a synergistic action of the individual components of nanosystems and the drug and demonstrating the potential application of the proposed nanomedicine for the treatment of inflammation.

Development and Application of an Advanced Biomedical Material-Silk Sericin.

Sericin, a protein derived from silkworm cocoons, is considered a waste product derived from the silk industry for thousands of years due to a lack of understanding of its properties. However, in recent decades, a range of exciting properties of sericin are studied and uncovered, including cytocompatibility, low-immunogenicity, photo-luminescence, antioxidant properties, as well as cell-function regulating activities. These properties make sericin-based biomaterials promising candidates for biomedical applications. This review summarizes the properties and bioactivities of silk sericin and highlights the latest developments in sericin in tissue engineering and regenerative medicine. Furthermore, the extended application of sericin in developing flexible electronic devices and 3D bioprinting is also discussed. It is believed that sericin-based biomaterials have great potential of being developed into novel tissue engineering products and smart implantable devices for various medical applications toward improving clinical outcomes.

The ratio of fibroin to sericin in the middle silk gland of Bombyx mori and its correlation with the extensional behavior of the silk dope.

Understanding how native silk spinning occurs is crucial for designing artificial spinning systems. One often overlooked factor in Bombyx mori is the secretion of sericin proteins. Herein, we investigate the variation in amino acid content at different locations in the middle silk gland (MSG) of B. mori. This variation corresponds to an increase in sericin content when moving towards the anterior region of the MSG, while the posterior region predominantly contains fibroin. We estimate the mass ratio of sericin to fibroin to be ~25/75 wt% in the anterior MSG, depending on the fitting method. Then, we demonstrate that the improvement in the extensional behavior of the silk dope in the MSG correlates with the increase in sericin content. The addition of sericin may decrease the viscosity of the silk dope, a factor associated with an increase in the spinnability of silk. We further discuss whether this effect could also result from other known physicochemical changes within the MSG.

Bioactive self-assembling silk fibroin-sericin films for skin tissue engineering.

The quest for an ideal wound dressing material has been a strong motivation for researchers to explore novel biomaterials for this purpose. Such explorations have led to the extensive use of silk fibroin (SF) as a suitable polymer for several applications over the years. Unfortunately, another major silk protein-sericin has not received its due attention yet in spite of having favorable biological properties. In this study, we report an approach of blending SF and silk sericin (SS) without the usage of chemical crosslinkers is made possible by the usage of formic acid which evaporates to induceß-sheets formation to form cytocompatible films. Raman spectroscopy confirms the presence of SF/SS components in blend and formation ofß-sheet in films.In situ, gelation kinetics studies were conducted to understand the change in gelation properties with addition of sericin into SF. Methyl thiazolyl tetrazolium and live/dead assays were performed to study cellular attachment, viability and proliferation on SF/SS films. The antibacterial properties of SF/SS films were tested using Gram-negative and Gram-positive bacteria. The re-structured SF/SS films were stable, transparent, show good mechanical properties, antibacterial activity and cytocompatibility, therefore can serve as suitable biomaterial candidates for skin regeneration applications.

κ-Carrageenan/sericin polymer matrix modified with different crosslinking agents and thermal crosslinking: Improved release profile of mefenamic acid.

The crosslinking of the polymer matrix with compatible macromolecules results in a three-dimensional network structure that offers an enhancement in the controlled release properties of the material. In this sense, this work aimed to improve the release profile of mefenamic acid (MAC) through crosslinking strategies. κ-Carrageenan/sericin crosslinked blend was obtained by covalent and thermal crosslinking and the different formulations were characterized. The gastroresistant potential and release profile were evaluated in the dissolution assay. The effect and characterization of the particles were investigated. Multiple units presented high entrapment efficiency (94.11-104.25), high drug loading (36.50-47.50 %) and adequate particle size (1.34-1.57 mm) with rough surface and visually spherical shape. The Weibull model showed that drug release occurred by relaxation, erosion and Fickian diffusion. Material stability and absence of MAC -polymer interactions were demonstrated by FTIR and thermogravimetric analysis. DSC showed a stable character of MAC in the drug-loaded beads. Moreover, the application studies of κ-Car/Ser/carboxymethylcellulose in the in vitro intestine mode showed that the crosslinked blend increased cell viability (>85 %), while free MAC exhibited a cytotoxic effect. Finally, the crosslinked k-Car/Ser blend MAC -loaded showed promising properties of a sustained release form of anti-inflammatory drug.

A novel injectable sericin hydrogel with strong fluorescence for tracing.

Hydrogel systems with strong fluorescence, as convenient tracers or bio-probes, have attracted much attention in biomedical engineering. Currently, most hydrogels endowed fluorescent properties due to modifying additional fluorophores. However, these fluorophores owing to photobleaching and toxicity limit the practical applications of hydrogels. Herein, we prepared a novel self-luminescence hydrogel through double crosslinking glutaraldehyde and hydrogen peroxide/horseradish peroxidase (H2O2/HRP) with sericin protein. The double cross-linked sericin hydrogel exhibits strong green and red intrinsic fluorescence which can be excited over a wide range of wavelengths. Moreover, this hydrogel with strong intrinsic fluorescence could penetrate thick pigskin tissue, which has potential application in implantable bio-tracer areas. In addition to the above unique properties, this sericin hydrogel possesses two types of micropore structures with high porosity, swelling properties, pH-responsive degradability, super elasticity, injectability, viscosity, and excellent biocompatibility. The investigation could significantly expand the scope of protein hydrogels in biomedical applications.

Fabrication, Structural Characteristics, and Properties of Sericin-Coated Wool Nonwoven Fabrics.

Recently, nonwoven fabrics from natural silk have attracted considerable attention for biomedical and cosmetic applications because of their good mechanical properties and cytocompatibility. Although these fabrics can be easily fabricated using the binding character of sericin, the high cost of silk material may restrict its industrial use in certain areas. In this study, sericin was added as a binder to a cheaper material (wool) to prepare wool-based nonwoven fabrics and investigate the effect of the amount of sericin added on the structural characteristics and properties of the wool nonwoven fabric. It was found using SEM that sericin coated the surface of wool fibers and filled the space between them. With an increase in sericin addition, the porosity, moisture regain, and the contact angle of the sericin-coated wool nonwoven fabric decreased. The maximum stress and initial Young's modulus of the nonwoven fabric increased with the increase in sericin amount up to 32.5%, and decreased with a further increase in the amount of sericin. Elongation at the end steadily decreased with the increase in sericin addition. All of the nonwoven fabrics showed good cytocompatibility, which increased with the amount of sericin added. These results indicate that sericin-coated wool-based nonwoven fabrics may be successfully prepared by adding sericin to wool fibers, and that the properties of these fabrics may be diversely controlled by altering the amount of sericin added, making them promising candidates for biomedical and cosmetic applications.

Codelivery of resveratrol melatonin utilizing pH responsive sericin based nanocarriers inhibits the proliferation of breast cancer cell line at the different pH.

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.

Fabrication, Structure, and Properties of Nonwoven Silk Fabrics Prepared with Different Cocoon Layers.

In this study, five different nonwoven silk fabrics were fabricated with silk fibers from different cocoon layers, and the effect of the cocoon layer on the structural characteristics and properties of the nonwoven silk fabric was examined. The diameter of the silk fiber and thickness of the nonwoven silk fabric decreased from the outer to the inner cocoon layer. More amino acids with higher hydrophilicity (serine, aspartic acid, and glutamic acid) and lower hydrophilicity (glycine and alanine) were observed in the outer layers. From the outer to the inner layer, the overall crystallinity and contact angle of the nonwoven silk fabric increased, whereas its yellowness index, moisture retention, and mechanical properties decreased. Regardless of the cocoon layer at which the fiber was sourced, the thermal stability of fibroin and sericin and good cell viability remained unchanged. The results of this study indicate that the properties of nonwoven silk fabric can be controlled by choosing silk fibers from the appropriate cocoon layers. Moreover, the findings in this study will increase the applicability of nonwoven silk fabric in the biomedical and cosmetic fields, which require specific properties for industrialization.

Evaluation of Antibacterial Mechanism of Action, Tyrosinase Inhibition, and Photocatalytic Degradation Potential of Sericin-Based Gold Nanoparticles.

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.

A high molecular weight silk fibroin scaffold that resists degradation and promotes cell proliferation.

The regulation of the biodegradation rate of 3D-regenerated silk fibroin scaffolds and the avoidance of premature collapse are important concerns for their effective applications in tissue engineering. In this study, bromelain, which is specific to sericin, was used to remove sericin from silk, and high molecular weight silk fibroin was obtained after the fibroin fibers were dissolved. Afterwards, a 3D scaffold was prepared via freeze-drying. The Sodium dodecyl sulfate-polyacrylamide gel electrophoresis results showed that the average molecular weight of the regenerated silk fibroin prepared by using the bromelain-degumming method was approximately 142.2 kDa, which was significantly higher than that of the control groups prepared by using the urea- and Na2 CO3 -degumming methods. The results of enzyme degradation in vitro showed that the biodegradation rate and internal three-dimensional structure collapse of the bromelain-degumming fibroin scaffolds were significantly slower than those of the two control scaffolds. The proliferation activity of human umbilical vein vascular endothelial cells inoculated in bromelain-degumming fibroin scaffolds was significantly higher than that of the control scaffolds. This study provides a novel preparation method for 3D-regenerated silk fibroin scaffolds that can effectively resist biodegradation, continuously guide cell growth, have good biocompatibility, and have the potential to be used for the regeneration of various connective tissues.

Resveratrol loaded native silk fiber-sericin hydrogel double interpenetrating bioactive wound dressing facilitates full-thickness skin wound healing.

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 activitiesin 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 SPDin vitro, effectivein vivotreatment 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.

Switchable hepatic organelles aberrations in DEN-induced mice under the influence of chemically characterized silk sericin.

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.

A native sericin wound dressing spun directly from silkworms enhances wound healing.

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.

Enhanced biocompatibility of silk sericin/caffeic acid nanoparticles by red blood cell membranes cloaking.

Caffeic acid (CA) is an antioxidant phenolic compound that enriched in coffee beans, however, its administration often restrains by the instability and low solubility. Nanoparticle encapsulation is an effective approach to improve the therapeutic activity of CA. For example, silk sericin (SS), a natural biomaterial finds applications in food, cosmetics and biomedical fields, is proved here to be an appropriate encapsulation agent for CA, and a SS/CA composite nanoparticle has been fabricated. To further improve the biocompatibility of SS/CA, a red blood cell membranes (RM) cloaking strategy is adopted. The as-formed SS/CA/RM preserves the antioxidant activity of CA, and shows satisfactory biocompatibility especially under high concentration. Hope this can provide a potential appropriative strategy to adjust the chemical stability of insoluble drugs and to improve their biocompatibility.

Silk Fibroin and Sericin Differentially Potentiate the Paracrine and Regenerative Functions of Stem Cells Through Multiomics Analysis.

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.