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The prospective applications of chitosan-based hydrogels (CBHs), a category of biocompatible and biodegradable materials, in biomedical disciplines such as tissue engineering, wound healing, drug delivery, and biosensing have garnered great interest. The synthesis and characterization processes used to create CBHs play a significant role in determining their characteristics and effectiveness. The qualities of CBHs might be greatly influenced by tailoring the manufacturing method to get certain traits, including porosity, swelling, mechanical strength, and bioactivity. Additionally, characterization methods aid in gaining access to the microstructures and properties of CBHs. Herein, this review provides a comprehensive assessment of the state-of-the-art with a focus on the affiliation between particular properties and domains in biomedicine. Moreover, this review highlights the beneficial properties and wide application of stimuli-responsive CBHs. The main obstacles and prospects for the future of CBH development for biomedical applications are also covered in this review.

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.

Bombyx mori nuclear polyhedrosis virus (BmNPV) is the most damaging virus for the production of silkworm cocoons. Antivirus research continues to be an important aspect of the silkworm industry. Two-dimensional electrophoresis and mass spectrometry have been applied for analyzing the midgut proteome of BmNPV-infected silkworms. In recent years, the isobaric tags for relative and absolute quantitation (iTRAQ) method has frequently been used when studying interaction between BmNPV and Bombyx mori, and useful information has been obtained. In this study, midgut proteins of BmNPV-infected silkworms were extracted from silkworm variety NIL·LVR with anti-BmNPV activity at 48 h, and proteome analysis was carried out using the label-free method. 2196 proteins were identified. Among them, there were 85 differentially expressed proteins, 45 upregulated proteins (immune-activated proteins), 28 downregulated proteins, and six proteins were specific for the BmNPV group and another six specific for control group. Many of the immune-activated proteins have been reported to have innate immune functions, and the downregulated proteins are involved in apoptosis or abnormal cell viability. In conclusion, this study provides evidence for host defense against BmNPV infection by both innate immunity and apoptosis, revealing the potential function of the midgut after oral infection of BmNPV in Bombyx mori. Significance Bombyx mori nuclear polyhedrosis virus (BmNPV) has a great impact on the sericulture industry. However, the mechanism of resistance to BmNPV has not been fully elucidated. The silkworm midgut is not only the major organ for food digestion and nutrient absorption but also an immune organ serving as the first line of defense against microbial invasion and proliferation. Here we combined label-free quantitative proteomic, bioinformatics, quantitative real-time PCR and SDS-PAGE analyses and found that BmNPV invasion causes complex protein alterations in the larval midgut of NIL·LVR with anti-BmNPV activity. The results showed that many upregulated differentially expressed proteins have been reported to have innate immune functions and the downregulation proteins are involved in apoptosis or abnormal cell viability. These findings provide evidence for host defense against BmNPV infection by both innate immunity and apoptosis, and reveals the potential function of the midgut after infection of BmNPV in Bombyx mori.

Sericin, a bioactive protein forming the outer layer of silk, promotes cell proliferation and cell adhesion, inhibits inflammation, and provides nutrition. Here, we obtain endotoxin-free sericin and explore its potential property in antiviral activity towards infectious diseases. In vesicular stomatitis virus (VSV) infection model, pre-treatment with sericin obviously inhibits VSV replication and reduces organ injury in infected mice. Further studies reveal that pre-incubating cells with sericin results in suppressing the infections of VSV and Enterovirus 71 (EV71) in infected cells. More evidences show that upon virus infection, the levels of interferons (IFNs) are significantly elevated in the cells pre-incubated with sericin as compared to untreated cells, indicating that sericin promotes virus-induced antiviral immune responses. Mechanistically, sericin attenuates cell glycolysis rate and reduces lactate production. Low level of lactate benefitting from sericin treatment facilitates the RIG-I-MAVS signaling pathway to initiate interferon activation. Notably, like sericin, a sericin-derived peptide F5-SP shares the same functions to exert antiviral activity both in vitro and in vivo. Therefore, we report that sericin and sericin-derived peptide F5-SP enhance antiviral innate immune response through inhibiting lactate production, which discovers a promising biomedical application of sericin in the prevention and treatment of viral infectious diseases.

Applications of cyanidin-3-O-glucoside (C3G) are limited due to the poor stabilities. In this work, we proposed using silk fibroin peptide (SFP) to bind with C3G and form nanocomposites (134.73 ± 4.51 nm) for stabilization. When interacted with C3G, the fluorescence of SFP contributed by tyrosine and phenylalanine amino acids was quenched, which was proved a static quenching with the β-sheet structure of SFP unchanged. With the further exploration of the physicochemical stabilities of C3G in the nanocomposites, we demonstrated that the tolerance of C3G to the alkaline environment and the retention ratio of C3G in various concentrations of metallic ion Cu2+ were significantly improved. In addition, the heat resistance of C3G in SFP at 80 °C was also enhanced with up to an increase of 2.5 times for the average half-life of C3G. Our results shed light on SFP could enhance physicochemical stabilities of C3G with maintaining its antioxidant activity.

High transparent and biocompatible hydrogel dressing with bioactivity is attractive for clinical skin repair. Here we report a high optically transparent interpenetrating network (IPN) hydrogel that was fabricated by sericin and polyacrylamide. The hydrogels possess pH-dependent degradation as well as high porosity and porous structures with different sized diameters and distribution. Moreover, the swelling behaviors, degradation dynamics, and mechanical strength can be flexibly regulated by adjusting the content of sericin. In addition, the hydrogel system is compatible with hosting cells owing to its excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival. Together, our study demonstrates that the sericin-polyacrylamide interpenetrating network hydrogel may serve as a visualized dressing material for real-time monitoring of wounds.

A wafer‐scale high resolution patterning of bio‐microstructures is achieved using precise protein photolithography. In article number 1700191, the application of these micropatterned structures as cellular substrate for the successful spatial guidance of fetal neural stems cells using well‐defined silk fibroin light chain as the resist material is demonstrated by Tiger H. Tao and co‐workers.

Precise patterning of biomaterials has widespread applications, including drug release, degradable implants, tissue engineering, and regenerative medicine. Patterning of protein‐based microstructures using UV‐photolithography has been demonstrated using protein as the resist material. The Achilles heel of existing protein‐based biophotoresists is the inevitable wide molecular weight distribution during the protein extraction/regeneration process, hindering their practical uses in the semiconductor industry where reliability and repeatability are paramount. A wafer‐scale high resolution patterning of bio‐microstructures using well‐defined silk fibroin light chain as the resist material is presented showing unprecedent performances. The lithographic and etching performance of silk fibroin light chain resists are evaluated systematically and the underlying mechanisms are thoroughly discussed. The micropatterned silk structures are tested as cellular substrates for the successful spatial guidance of fetal neural stems cells seeded on the patterned substrates. The enhanced patterning resolution, the improved etch resistance, and the inherent biocompatibility of such protein‐based photoresist provide new opportunities in fabricating large scale biocompatible functional microstructures.

In materials science and engineering, designed and well-ordered self-assembled hydrogel with excellent biocompatibility and nontoxic properties is an inviting issue. In this study, a novel self-assembled sericin hydrogel was prepared by a simple-two-step process containing milling and high temperature and high pressure. It is worthwhile pointing out that the sericin with high extraction rate (95%) for fabricating sericin hydrogel was isolated from fibroin-deficient mutant silk cocoons. The hydrogel was formed under a mild condition without introducing any other toxic or harmful substances and its gelling time could be controlled by sericin concentration, temperature or pH values. Moreover, as long as the sericin solution is kept in a bioclean circumstance, the sterile sericin hydrogel can be achieved and no need to sterilize. Furthermore, this hydrogel possesses high porosity, degradation. In addition, the hydrogel system is suitable as a carrier of cells or bioactive molecules contribute from its excellent cell-adhesive capability, effectively promoting cell attachment, proliferation, and a sustained manner for drug release. In summary, our study indicates that the self-assembly sericin hydrogel could be promising candidates in soft tissue engineering applications.

A high optically transparent pure sericin hydrogel without any harmful or toxic ingredients is attractive for cell culture system and drug delivery. Here we report a novel 3D pure sericin hydrogel fabricated using ultrasonication method. Gelation time of the hydrogel could be controlled from minutes to days by regulated sonication parameters, including power output and time, as well as sericin concentration. This hydrogel possesses high optically transparence, injectability, eximious elasticity, pH-dependent degradation as well as high porosity. In addition, the hydrogel system is compatible for hosting cell and bioactive molecules owing to its excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival, along with delivering bioactive reagent in a sustained manner. Together, our study demonstrates that the sericin hydrogel may serve as a multifunctional platform for cell culture and drug delivery.

In this study, we report a novel cellulase [β-1,4-endoglucanase (EGase), EC 3.2.1.4] cDNA (Bh-EGase II) belonging to the glycoside hydrolase family (GHF) 45 from the beetle Batocera horsfieldi. The Bh-EGase II gene spans 720 bp and consists of a single exon coding for 239 amino acid residues. Bh-EGase II showed 93.72% protein sequence identity to Ag-EGase II from the beetle Apriona germari. The GHF 45 catalytic site is conserved in Bh-EGase II. Bh-EGase II has three putative N-glycosylation sites at 56–58 (N–K–S), 99–101 (N–S–T), and 237–239 (N–Y–S), respectively. The cDNA encoding Bh-EGase II was expressed in baculovirus-infected insect BmN cells and Bombyx mori larvae. Recombinant Bh-EGase II from BmN cells and larval hemolymph had an enzymatic activity of approximately 928 U/mg. The enzymatic catalysis of recombinant Bh-EGase II showed the highest activity at 50 °C and pH 6.0.

Although alginate hydrogels have been extensively studied for tissue engineering applications, their utilization is limited by poor mechanical strength, rapid drug release and a lack of cell adhesive ability. Aiming to improve these properties, we employ the interpenetrating hydrogel design rationale. Using alginate and sericin (a natural protein with many unique properties and a major component of silkworm silk), we develop an interpenetrating polymer network (IPN) hydrogel comprising interwoven sericin and alginate double networks. By adjusting the sericin-to-alginate ratios, IPNs’ mechanical strength can be adjusted to meet stiffness requirements for various tissue repairs. The IPNs with high sericin content show increased stability during degradation, avoiding pure alginate’s early collapse. These IPNs have high swelling ratios, benefiting various applications such as drug delivery. The IPNs sustain controlled drug release with the adjustable rates. Furthermore, these IPNs are adhesive to cells, supporting cell proliferation, long-term survival and migration. Notably, the IPNs inherit sericin’s photoluminescent property, enabling bioimaging in vivo. Together, our study indicates that the sericin-alginate IPN hydrogels may serve as a versatile platform for delivering cells and drugs and suggests that sericin may be a building block broadly applicable for generating IPN networks with other biomaterials for diverse tissue engineering applications.

Cranial fixation should be safe, reliable, ideally degradable, and produce no hazardous residues and no artifacts on neuroimaging. Protein-based fixation devices offer an exciting opportunity for this application. Here, the preclinical development and in vivo efficacy verification of a silk cranial fixation system in functional models are reported by addressing key challenges toward clinical use. A comprehensive study on this fixation system in rodent and canine animal models for up to 12 months is carried out. The silk fixation system shows a superb performance on the long-term stability of the internal structural support for cranial flap fixation and bone reconnection and has good magnetic resonance imaging compatibility, and tolerability to high dose radiotherapy, underscoring the favorable clinical application of this system for neurosurgery compared to the current gold standard.

Precise patterning of biomaterials has widespread applications, including drug release, degradable implants, tissue engineering, and regenerative medicine. Patterning of protein-based microstructures using UV-photolithography has been demonstrated using protein as the resist material. The Achilles heel of existing protein-based biophotoresists is the inevitable wide molecular weight distribution during the protein extraction/regeneration process, hindering their practical uses in the semiconductor industry where reliability and repeatability are paramount. A wafer-scale high resolution patterning of bio-microstructures using well-defined silk fibroin light chain as the resist material is presented showing unprecedent performances. The lithographic and etching performance of silk fibroin light chain resists are evaluated systematically and the underlying mechanisms are thoroughly discussed. The micropatterned silk structures are tested as cellular substrates for the successful spatial guidance of fetal neural stems cells seeded on the patterned substrates. The enhanced patterning resolution, the improved etch resistance, and the inherent biocompatibility of such protein-based photoresist provide new opportunities in fabricating large scale biocompatible functional microstructures.

Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine.

White egg 2 is one of white egg mutants in silkworm, whose molecular mechanism remains unknown so far. In order to obtain an overall view on gene expression profiles at early embryo development stages, the white egg 2 near-isogenic line was constructed and the whole-genome of silkworm microarray system containing 21375 predicted genes from the silkworm whole genome sequence was employed to investigate gene expression profiles at 0, 24 and 48 h post oviposition between white egg 2 mutant and normal black egg strain. At 24 h post oviposition, 49 genes exhibited at least 2.0 fold differences at expression level, including 24 up-regulated genes and 25 down-regulated genes while at 48 h post oviposition, 52 genes, including 23 up-regulated genes and 29 down-regulated genes were expressed differentially over 2.0 change fold. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that nine differentially expression genes were involved in nine significant (p

A set of biocompatible, biodegradable, and biofunctionalizable diffractive optical elements (DOEs) using silk proteins as the building materials is reported. The diffraction pattern of a DOE is highly sensitive to the surrounding environment and the structural integrity, offering numerous opportunities for biosensing applications.