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

Year: 2025

Type: article

Abstract: A reliable, clinically meaningful engineered skin for permanent wound closure does not currently exist. Previously, we showed that a hydrogel formed from human platelets (platelet gel - PG) and populated with fibroblasts, can provide a niche for interfollicular stem and progenitor keratinocytes in vitro. The so-called platelet-derived Human Skin Equivalent (PG-HSE) was developed as a semi-mature bilaminar engineered skin with both neo-dermis and neo-epidermis.In this study, PG-HSE graftability to permanently close full thickness wound was tested in a NUDE mouse model. This was compared to the graftability of an engineered skin using a synthetic scaffold, NovoSorb® polyurethane biodegradable temporising matrix (BTM-HSE). Full thickness wounds on the dorsum of Nude mice were grafted with either PG-HSE, BTM HSE or native skin. Grafts were analysed macroscopically, histologically and at the molecular level, two weeks post-grafting.Two weeks post grafting, inflammatory markers CXCl1, CXCl2, IL1β, IL-6 had dropped in PG-HSE grafts, to similar levels seen in autologous native skin grafts. This allowed PG-HSE grafts to progress effectively to the next phase of wound repair. Immunofluorescence using a human-specific involucrin antibody showed complete wound closure and near native epidermal maturation pattern in PG-HSE grafts in two weeks. This coincided with higher collagen synthesis, particularly Col I and Col III in the PG-HSE grafted wound bed, compared to BTM-HSE grafts. Importantly, the antimicrobial effect of PG may improve its clinical suitability.In this study, we demonstrated engineered PG-HSE as a reliable and sustainable solution for full thickness wound closure in a preclinical mouse model, which warrants its testing in clinics where skin donor site availability is limited.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26209988