RESUMO
Silk, a natural biopolymer, has been used clinically as suture material over thousands of years and has received much impetus for a plethora of biomedical applications in the last two decades. Silk protein isolated from both mulberry and nonmulberry silkworm varieties gained recognition as a potential biomaterial owing to its affordability and remarkable physicochemical properties. Molecular studies on the amino acid composition and conformation of silk proteins interpreted in the present review provide a critical understanding of the difference in crystallinity, hydrophobicity, and tensile strength among silkworm silk proteins. Meticulous silk fibroin (SF) isolation procedures and innovative processing techniques to fabricate gamut of two-dimensional (2D) and three-dimensional (3D) matrices including the latest 3D printed scaffolds have led SF for diverse biomedical applications. Crucial factors for clinical success of any biomaterial, including biocompatibility, immune response, and biodegradability, are discussed with particular emphasis on the lesser-known endemic nonmulberry silk varieties, which in recent years have gained considerable attention. The tunable biodegradation and bioresorbable attributes of SF enabled its use in drug delivery systems, thus proving it as an efficient and specific vehicle for controlled drug release and targeted drug delivery. Advancements in fabrication methodologies inspired biomedical researchers to develop SF-based in vitro tissue models mimicking the spatiotemporal arrangement and cellular distribution of native tissue. In vitro tissue models own a unique demand for studying tissue biology, cellular crosstalks, disease modeling, drug designing, and high throughput drug screening applications. Significant progress in silk biomaterial research has evolved into several silk-based healthcare products in the market. Insights of silk-based products assessed in the human clinical trials are presented in this review. Overall, the current review explores the paradigm of the silk structure-function relationship driving silk-based biomaterials toward tissue engineering, drug delivery systems, and in vitro tissue models.
RESUMO
Islet transplantation is considered the most promising treatment for type 1 diabetes. However, the clinical success is limited by islet dysfunction in long-term culture. In this study, we have utilized the rapid self-gelation and injectability offered by blending of mulberry silk (Bombyx mori) with non-mulberry (Antheraea assama) silk, resulting in a biomimetic hydrogel. Unlike the previously reported silk gelation techniques, the differences in amino acid sequences of the two silk varieties result in accelerated gelation without requiring any external stimulus. Gelation study and rheological assessment depicts tuneable gelation as a function of protein concentration and blending ratio with minimum gelation time. In vitro biological results reveal that the blended hydrogels provide an ideal 3D matrix for primary rat islets. Also, A. assama fibroin with inherent Arg-Gly-Asp (RGD) shows significant influence on islet viability, insulin secretion and endothelial cell maintenance. Furthermore, utility of these hydrogels demonstrate sustained release of Interleukin-4 (IL-4) and Dexamethasone with effective M2 macrophage polarization while preserving islet physiology. The immuno-informed hydrogel demonstrates local modulation of inflammatory responses in vivo. Altogether, the results exhibit promising attributes of injectable silk hydrogel and the utility of non-mulberry silk fibroin as an alternative biomaterial for islet encapsulation.