Porcine plasma protein cold-set hydrogel crosslinked by genipin and the immunomodulatory, proliferation promoting and scar-remodeling in wound healing.

Addressing the critical need for biocompatible and multifunctional wound dressings for chronic and non-healing wounds, cold-set hydrogel using natural biomacromolecules are potential candidates. This study developed a novel cold-set hydrogel of porcine plasma protein (PPP) through genipin (GP) as crosslinker and glucono delta-lactone (GDL) as acidifier. GP promoted hardness, springiness, water holding capacity (WHC) and modulus in a dose-dependent manner in the presence of GDL, and significantly enhanced microstructural density, integrity and anti-degradation, critical as wound dressing, achieving the optimal performance at 0.15 % GP and 0.2 % GDL. Subsequently, biocompatibility assessments revealed that the optimum PPP gel was low cytotoxicity and could support cell migration and proliferation, reduce apoptosis with dose-effect relationship of the filler PPP. Meanwhile, in vivo skin wound healing model indicated the efficacy in accelerating wound healing, reducing inflammation, and promoting tissue remodeling without excessive scar formation. These effects are attributed to the ability of PPP in the hydrogel to modulate local inflammatory responses, enhance angiogenesis, and balance extracellular matrix remodeling processes. In conclusion, this pioneering work establishes PPP cold-set hydrogels as promising candidates for advanced wound care solutions, combining the benefits of natural protein-based biomaterials with innovative crosslinking strategies to meet urgent clinical needs in regenerative medicine.