Multifunctional integrally-medicalized hydrogel system with internal synergy for efficient tissue regeneration

Hydrogel has been used in drug delivery systems because of its excellent porosity, biocompatibility, and water retention. However, it remains challenging to medicalize hydrogels and construct an integrated therapeutic system to significantly boost efficiency. Using bovine serum albumin (BSA) and gelatin crosslinked via copper sulfate (Cu2+) with a thiol group (-SH), we developed [email protected]2+-REG, a multifunctional integrally-medicalized hydrogel, as an injectable scaffold loading the functional peptide REGRT (REG), which considerably accelerated vascularization and tissue regeneration. Additionally, Cu2+ ions were used as cross-linkers providing antibacterial activity, while the hypoxia-inducible factor (HIF)-1α conferred protection from Cu2+ ions and assisted REG in upregulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP2) for angiogenesis and wound healing. Furthermore, the easily biodegradable BSA and gelatin provide an appropriate drug release rate and promote cell adhesion. We determined that [email protected]2+-REG possessed internal synergy and acted as a thruster for rapid angiogenesis and tissue regeneration, a desired feature in the prognosis of flap transplantation as well as in other surgeries associated with trauma treatment.