Nonmulberry silk fibroin-based biomaterials: Impact on cell behavior regulation and tissue regeneration

Silk fibroin (SF) is a promising biomaterial due to its good biocompatibility, easy availability, and high mechanical properties. Compared with mulberry silk fibroin (MSF), nonmulberry silk fibroin (NSF) isolated from typical nonmulberry silkworm silk exhibits unique arginine-glycine-aspartic acid (RGD) sequences with favorable cell adhesion enhancing effect. This inherent property probably makes the NSF more suitable for cell culture and tissue regeneration-related applications. Accordingly, various types of NSF-based biomaterials, such as particles, films, fiber mats, and 3D scaffolds, are constructed and their application potential in different biomedical fields is extensively investigated. Based on these promising NSF biomaterials, this review firstly makes a systematical comparison between the molecular structure and properties of MSF and typical NSF and highlights the unique properties of NSF. In addition, we summarize the effective fabrication strategies from degummed nonmulberry silk fibers to regenerated NSF-based biomaterials with controllable formats and their recent application progresses in cell behavior regulation and tissue regeneration. Finally, current challenges and future perspectives for the fabrication and application of NSF-based biomaterials are discussed. Related research and perspectives may provide valuable references for designing and modifying effective NSF-based and other natural biomaterials. STATEMENT OF SIGNIFICANCE: There exist many reviews about mulberry silk fibroin (MSF) biomaterials and their biomedical applications, while that about nonmulberry silk fibroin (NSF) biomaterials is scarce. Compared with MSF, NSF exhibits unique arginine-glycine-aspartic acid sequences with promising cell adhesion enhancing effect, which makes NSF more suitable for cell culture and tissue regeneration related applications. Focusing on these advanced NSF biomaterials, this review has systematically compared the structure and properties of MSF and NSF, and emphasized the unique properties of NSF. Following that, the effective construction strategies for NSF-based biomaterials are summarized, and their recent applications in cell behavior regulations and tissue regenerations are highlighted. Furthermore, current challenges and future perspectives for the fabrication and application of NSF-based biomaterials were discussed.