Bioactive and degradable hydrogel based on human platelet-rich plasma fibrin matrix combined with oxidized alginate in a diabetic mice wound healing model

Abstract

In the present study we developed an injectable, bioactive and degradable hydrogel composed of alginate at 2.5% oxidation degree and calcium-activated platelet rich plasma (PRP) for wound healing applications (PRP-HG-2.5%). The alginate gives mechanical support to the hydrogel while the activated PRP provides growth factors that enhance wound healing and fibrin which creates an adequate microenvironment for cell migration and proliferation. The rheological and mechanical properties of the hydrogel were characterized. Further characterization revealed that PRP-HG-2.5% showed a faster hydrolitic degradation rate than unmodified alginate and a similar platelet derived growth factor (PDGF-BB) release profile. In vitro efficacy studies, carried out in human fibroblasts and keratinocytes, showed that PRP-HG-2.5% was not cytotoxic and that it was able to promote cell adhesion and proliferation. Thereafter, in an in vivo full thickness wound healing study conducted in diabetic mice, no differences were found among PRP-HG-2.5% and its counterpart without PRP, likely due to the xenogeneic origin of the PRP. This hypothesis was validated in vitro, since a cytotoxic effect was observed after human PRP application to mouse fibroblasts. Therefore, PRP-HG-2.5% might be a promising strategy for chronic woundstreatment, although its effectiveness should be evaluated in a more reliable preclinical model.

Keywords: Chronic wound; Hydrogel; Platelet Rich Plasma.