Injectable self-crosslinking hyaluronic acid/silk fibroin blend hydrogel based on disulfide bond

Injectable hyaluronic acid (HA) hydrogels show significant potential for applications in soft tissue filling in vivo through minimally invasive interventions. However, HA hydrogels have several shortcomings, including weak bio-mechanical, rapid degradation, and poor cell affinity. In this study, sulfhydrylated HA (SH) and sulfhydrylated silk fibroin (SS) were self-crosslinked to form injectable SH/SS blend hydrogels with adjustable architecture and properties. The gelation time could be programmed from 0.4 to 32 h by varying the SH/SS mass ratio. FTIR analysis revealed that disulfide bonds mediated the formation of the blend hydrogels, in which SS was predominantly structured with β-sheet and significantly improved the mechanical robustness, and enzymatic degradation resistance of the blend hydrogels. The SH/SS hydrogels exhibited a Young's modulus of 1.2–10.9 kPa, showing a highly matched flexibility for various human soft tissues. The SH-containing hydrogels exerted low extrusion forces ranging from 2.3 to 4.6 N, which fall within the clinically acceptable range for injection. In vitro cell culture results demonstrated that the incorporation of SS significantly promoted the viability, migration and proliferation of encapsulated human umbilical vein endothelial cells (HUVECs). These appealing characteristics enable the SH/SS blend hydrogels as promising candidates for applications in soft tissue filling and regeneration.