Insight into Silk-Based Biomaterials: From Physicochemical Attributes to Recent Biomedical Applications

Abstract

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.

Emerging Silk Material Trends: Repurposing, Phase Separation and Solution-Based Designs

“…While the biomedical use of silk has spanned several millennia, silk did fall out of fashion with the advent of synthetic manmade fibers, in the erroneous belief that we are able to “beat” nature. However, over the past 20 years, interest has been renewed both in our fundamental understanding of silk and in its biomedical applications [ 12 , 13 ]. Today, more than 13,000 publications on this subject are at our fingertips, and the number continues to grow (PubMed accessed January 2021).…”

Bioinspired Materials for Wound Healing Application: The Potential of Silk Fibroin

“…Indeed, compared to other fibrous proteins such as collagen, fibroin offers multiple options for sterilization, such as ethylene oxide, γ-radiation and 70% ethanol. Autoclaving of fibroin scaffolds does not affect their structure and properties, while collagen denatures at these temperatures [ 133 , 134 ]. Moreover, compared to biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA), which can increase local pH and affect cellular processes due to the degradation products of aliphatic polyester, the protein biopolymers have degradation products mostly consisting of amino acids that can be resorbed by cells [ 134 ].…”

“…Autoclaving of fibroin scaffolds does not affect their structure and properties, while collagen denatures at these temperatures [ 133 , 134 ]. Moreover, compared to biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA), which can increase local pH and affect cellular processes due to the degradation products of aliphatic polyester, the protein biopolymers have degradation products mostly consisting of amino acids that can be resorbed by cells [ 134 ]. Moreover, the degradation of silk can be controlled in function of processing parameters and crystallinity [ 132 ].…”

Spider Silk for Tissue Engineering Applications

“…A suitable substrate and scaffold for tissue engineering must support cell activities, such as adhesion, migration, proliferation, and differentiation [31,32]. Nowadays, in vitro cell culture studies, such as two-dimensional (2D), as well as three-dimensional (3D) scaffolds, have been evaluated.…”