A well defect-suitable and high-strength biomimetic squid type II gelatin hydrogel promoted in situ costal cartilage regeneration via dynamic immunomodulation and direct induction manners.

Reconstructing segmental costal cartilage defects resulting from autologous cartilage grafts in plastic surgery remains a challenge. The present study focused on a biomimetic strategy for in situ costal cartilage regeneration that did not rely on an autogenous/xenogenous tissue graft. A multifunctional biomimetic SGII/HA-DN hydrogel based on a "chemical-curing, shaping, and light-curing" gelation system was developed and evaluated for its mechanical properties, clinical applications and biological functions. This hydrogel showed good suitability to repair defects and a high mechanical support strength (11 MPa, which is close to the natural strength of costal cartilage). Biologically, the hydrogel exhibited dual-immunomodulatory effects on the pro-inflammatory/anti-inflammatory phenotypes of neutrophils and M1/M2 macrophage polarization and subsequently promoted the chondrogenesis of cartilage stem/progenitor cells through both direct induction and indirect stimulation by the M2 macrophage-mediated TGF-β/Smad pathway. Furthermore, this SGII/HA-DN hydrogel could regulate the local microenvironment, inducing new costal cartilage regeneration in vivo. Our findings demonstrate that the newly developed multifunctional SGII/HA-DN hydrogel provides a strategy with high prospect for the biomimetic repair of segmental costal cartilage defects in clinical practice.