644 Advancements in Biofabrication of Human Skin and Its Microvascularity

Abstract Aim Bioengineered in-vitro human skin substitutes with reliable “take” has been the aspiration of clinicians and bioengineering researchers when tackling compromised skin in chronic wounds, burns, malignancy and trauma. Microvasculature of these artificial models is key for maintaining hold into the recipient site. The purpose of this review is to outline the current body of literature regarding skin substitutes and innovations in bioengineered vascularity. Method A narrative literature review using a systematic approach was performed by using a search strategy and MESH terms: "((3D Bioprinting) OR (Biofabrication) OR (tissue engineering)) AND ((skin tissue) OR (skin substitutes) OR (human skin))". MEDLINE (PubMed), Embase (OVID) and CENTRAL (cochrane library) databases were examined. Inclusion and exclusion criteria were applied. Results Previous developments in 3D bioprinting involved forming multilayered scaffolds, hydrogel/gelatine bioinks, preset moulds with tissue-engineered keratinocytes and fibroblasts. Artificial angiogenesis in-vitro models have included lining biofabricated microtubules or pores with human placental pericytes or endothelial cells. Extrusion-based bioprinting has been popular either in a "top-down" or "bottom-up" approach to construct scaffolds. Pore size diameters of these substitutes have adhered to 100µm. Autologous fat grafting has provided a viable microvascular option. Conclusions Only a few studies and clinical trials have managed to tackle the vascularity issue of human skin substitutes. Exploration into integration 3D bioprinted scaffolds, fat grafting with a bottom-up approach using micropores lined with endothelial cells provides promise for future research. Further studies must be undertaken to assess feasibility, cost and "take" of such grafts initially in human subjects with industry support.