Bioengineered Skin from a Platelet-Derived Hydrogel Repairs Full Thickness Wounds in a Pre-Clinical Mouse Model

Despite advancement in skin engineering, native skin grafting remains the gold standard in clinical settings. We have previously demonstrated that a platelet-derived hydrogel (PG) can act as a scaffold to engineer a semi-mature bilaminar human skin equivalent (PG-HSE). In this study, PG-HSE was grafted on full thickness wounds in athymic mice. PG-HSE was compared with native skin autografts and a clinically proven bilaminar skin graft that utilises a single layer NovoSorb^® polyurethane biodegradable temporising matrix (plus plasma) as the scaffold (BTM-HSE). The graft analysis revealed PG-HSE-grafted wounds were fully epidermised in two weeks and the level of inflammatory markers, <i>CXCl1</i>, <i>CXCl2</i>, <i>IL1β</i>, and <i>IL-6</i> transcripts, in grafts were at similar levels to their levels in autografts. This coincided with higher expression of <i>COL1A2</i>, <i>COL3A1</i>, and <i>COL5A1</i> transcripts in PG-HSE grafts, compared to autografts and BTM-HSE grafts. Moreover, a higher deposition of both Col I and Col III was detected in the PG-HSE graft wound bed, when compared to the BTM-HSE graft wound bed. Conversely, BTM-HSE grafts showed a higher level of integrins, <i>ITGA2</i>, <i>ITGA3</i>, <i>ITGA5</i>, <i>ITGA6</i>, <i>ITGAV</i>, and <i>ITGB1</i>, at the RNA level, suggesting a stronger cell-scaffold interaction. In summary, we have shown although both PG and single layer BTM foam (plus plasma) are effective scaffolds for skin engineering, some key aspects of wound repair, including a reduction in inflammation and an increase in collagen deposition, are achieved with the platelet-derived hydrogel. The long-term effect of these scaffolds on wound scarring remains to be investigated.