A novel porous hydrogel based on hybrid gelation for injectable and tough scaffold implantation and tissue engineering applications

Although there have been many advances in injectable hydrogels as scaffolds for tissue engineering or as payload-containing vehicles, the lack of adequate microporosity for the desired cell behavior, tissue integration, and successful tissue generation remains an important drawback. Herein, we describe an effective porous injectable system that allows in vivo formation of pores through conventional syringe injection at room temperature. This system is based on the differential melting profiles of photocrosslinkable salmon gelatin and physically crosslinked porogens of porcine gelatin, in which porcine gelatin porogens are solid beads, while salmon methacrylamide gelatin remains liquid during the injection procedure. After injection and photocrosslinking, the porogens were degraded in response to the physiological temperature, enabling the generation of a homogeneous porous structure within the hydrogel. The resultant porous formulations exhibited controlled gelation kinetics within a broad temperature window (18.5 ± 0.5 - 28.8 ± 0.8 °C), low viscosity (133 ± 1.4 - 188 ± 16 cP ), low force requirements for injectability (17 ± 0.3 - 39 ± 1 N), robust mechanical properties (100.9 ± 3.4 - 332 ± 13.2 kPa), and favorable cytocompatibility (>70 % cell viability). Remarkably, in vivo subcutaneous injection demonstrated the suitability of the system with appropriate viscosity and swift crosslinking to generate porous hydrogels. The resulting injected porous constructs showed favorable biocompatibility and facilitated cell infiltration for desirable tissue remodeling. Finally, the porous formulations exhibited favorable handling, easy deposition, and good shape fidelity when used as bioinks in 3D bioprinting technology. This injectable porous system serves as a platform for various biomedical applications, thereby inspiring future advances in cell therapy and tissue engineering.