Silks fibroin can be chemically modified through amino acid side chains to obtain methacrylated silk (Sil-MA). Sil-MA could be processed into a variety of scaffold forms and combine synergistically with other biomaterials to form composites vehicle. The advent of Sil-MA material has enabled impressive progress in the development of various scaffolds based on Sil-MA type to imitate the structural and functional characteristics of natural tissues. This review highlights the reasonable design and bio-fabrication strategies of diverse Sil-MA-based tissue constructs for regenerative medicine. First, we elucidate modification methodology and characteristics of Sil-MA. Next, we describe characteristics of Sil-MA hydrogels, and focus on the design approaches and formation of different types of Sil-MA-based hydrogels. Thereafter, we present an overview of the recent advances in the application of Sil-MA based scaffolds for regenerative medicine, including detailed strategies for the engineering methods and materials used. Finally, we summarize the current research progress and future directions of Sil-MA in regenerative medicine. This review not only delineates the representative design strategies and their application in regenerative medicine, but also provides new direction in the fabrication of biomaterial constructs for the clinical translation in order to stimulate the future development of implants.

The last decade has witnessed significant progress in the development of photosensitive polymers for in situ polymerization and 3D printing applications. Light-mediated sol-gel transitions have immense potential for tissue engineering applications as cell-laden materials can be crosslinked within minutes under mild environmental conditions. Silk fibroin (SF) is extensively explored in regenerative medicine applications due to its ease of modification and exceptional mechanical properties along with cytocompatibility. To efficiently design SF materials, the in vivo assembly of SF proteins must be considered. During SF biosynthesis, changes in pH, water content, and metal ion concentrations throughout the silkworm gland divisions drive the transition from liquid silk to its fiber form. Herein, we study the effect of the glycidyl-methacrylate-modified SF (SilkMA) solution pH on the properties and secondary structure of SilkMA hydrogels by testing formulations prepared at pH 5, 7, and 8. Our results demonstrate an influence of the prepolymer solution pH on the hydrogel rheological properties, compressive modulus, optical transmittance, and network swellability. The hydrogel pH did not affect the in vitro viability and morphology of human dermal fibroblasts. This work demonstrates the utility of the solution pH to tailor the SilkMA conformational structure development toward utility and function and shows the need to strictly control the pH to reduce batch-to-batch variability and ensure reproducibility.