From secondary intent to accelerated regenerative healing: emergence of the bio-intelligent scaffold vasculogenic strategy for skin reconstruction

This chapter introduces the concept of bio-intelligent scaffolds and discusses the development of smart matrix, a pro-angiogenic porous fibrin-alginate synthetic skin replacement scaffold. This was developed through a biological-led series of assays to optimise endothelial cell ingress. Fibrin was identified as a pro-migratory material. To fabricate scaffold structures, a formulation incorporating alginate as a bulking agent and a compatible surfactant mix was developed for foam formation. Stabilisation was achieved with glutaraldehyde-borohydride cross-linking. Smart matrix prototypes supported conduction of endothelial cells, fibroblasts and MSC over 48 h in vitro. Extended fibroblast culture within the scaffold did not induce a myofibroblast phenotype. In a porcine full thickness wound model, smart matrix prototypes integrated over 7 days, with rapid vascularisation, partly due to vasculogenesis deep within the scaffold structure. Single stage skin reconstruction with a split-thickness overgraft was achieved, with a non-scarring outcome. In a novel delayed porcine wound model both Matriderm and Smart Matrix activated healing but only Smart Matrix produced a normal histological neodermis. This bio-intelligent biomaterial scaffold can promote integrative vasculogenesis, leading to a rapid regenerative-type healing. This could offer important clinical benefit and enhance the quality of patient’s lives