Tissue-Specific Hydrogels for Three-Dimensional Printing and Potential Application in Peripheral Nerve Regeneration

Decellularized extracellular matrix hydrogel (dECM-G) has demonstrated its significant tissue-specificity, high biocompatibility, and versatile utilities in tissue engineering. However, the low mechanical stability and fast degradation are major drawbacks for its application in three-dimensional (3D) printing. Herein, we report a hybrid hydrogel system consisting of dECM-Gs and photocrosslinkable gelatin methacrylate (GelMA), which resulted in significantly improved printability and structural fidelity. These premixed hydrogels retained high bioactivity and tissue-specificity due to their containing dECM-Gs. More specifically, it was realized that the hydrogel containing dECM-G derived from porcine peripheral nerves (GelMA/pDNM-G) effectively facilitated neurite growth and Schwann cell migration from two-dimensional cultured dorsal root ganglion explants. The nerve cells were also encapsulated in the GelMA/pDNM-G hydrogel for 3D culture or underwent cell-laden bioprinting with high cell viability. The preparation of such GelMA/dECM-G hydrogels enabled the recapitulation of functional tissues through extrusion-based bioprinting, which holds great potential for applications in regenerative medicine.