Injectable Ultrasonication-Induced Silk Fibroin Hydrogel for Cartilage Repair and Regeneration

Abstract

Articular cartilage lacks both a nutrient supply and progenitor cells. Once damaged, it has limited self-repair capability. Cartilage tissue engineering provides a promising strategy for regeneration, and the use of injectable hydrogels as scaffolds has recently attracted much attention. Silk fibroin (SF) is an advanced natural material used to construct injectable hydrogels that are nontoxic and can be used efficiently in crosslinking applications. The objective of the present work was to develop an injectable hydrogel using SF in a novel one-step ultrasonication crosslinking method. Gelation kinetics and the characteristics of ultrasonication-induced SF (US-SF) hydrogels were systematically evaluated. The cytocompatibility of US-SF hydrogels was evaluated using rabbit chondrocytes, the Cell Counting Kit-8 testing, and immunofluorescence staining. Furthermore, the <i>in vivo</i> cartilage regenerative ability of US-SF hydrogels was confirmed following subcutaneous administration in nude mice and <i>in situ</i> injections in rabbit osteochondral defect models. These results suggest that US-SF hydrogels could be potential candidates for cartilage repair and regeneration. Impact statement Injectable silk fibroin hydrogel is a promising strategy for cartilage tissue engineering. The transition from solution state to gel state can be fabricated by both physical and chemical methods. However, the complexing protocol and toxicity of these methods remain hindrances to further application. In this study, a one-step ultrasonication method was developed. The novel ultrasonication-induced silk fibroin hydrogel showed satisfactory physicochemical and biomechanical properties. <i>In vitro</i> and <i>in vivo</i> experiments proved that it could promote cartilage regeneration, indicating that it may be a potential solution for cartilage repair and regeneration.