pH responsive THPS crosslinked injectable hydrogel with Cu-metformin sustained-release for accelerating wound healing

The utilitarian capacity of hydrogels in fostering a conducive milieu for cellular viability renders them a compelling alternative to conventional wound dressings. Nonetheless, the uncontrolled drug release exhibited by numerous drug-loaded hydrogel dressings often undermines their capacity for sustaining therapeutic efficacy over prolonged periods, while certain hydrogel formulations prove inadequate for addressing deep-seated wounds with low pH caused by chronic bacterial infections. Within the scope of this investigation, a novel pH-responsive injectable sustained-release hydrogel is developed through the crosslinking of tetrakis (hydroxymethyl) phosphonium sulfate (THPS) with carboxymethyl chitosan (CMCS) and Ɛ-poly-L-lysine (EPL). This innovative hydrogel manifests rapid gelation within a span of 30 s sans the requirement of a catalyst, alongside demonstrating commendable antibacterial attributes facilitated by the incorporation of a Cu-metformin complex (CuMet). Furthermore, the lyophilized hydrogel exhibits exceptional water absorbency and hemostatic qualities, effectively addressing exudative concerns and mitigating blood loss. In vitro assessments ascertain the higher drug release under acidic conditions and sustained drug release potential of CMCS/EPL/CuMet for up to 120 h, concomitantly expediting wound healing processes through the attenuation of bacterial colonization and inflammatory responses. In summation, this investigation furnishes novel insights into the viability of the developed formulation as a sustained-release injectable wound dressing.