Abstract
Autologous split-thickness skin grafts are the preferred treatment for excised burn wounds, but donor sites for autografting are often limited in patients with extensive burns. A number of alternative treatments are already in use to treat large burns and ulcers. Despite intense efforts to develop tissue-engineered skin, delayed or absent vascularization is one of the major reasons for tissue-engineered skin engraftment failure. To overcome these problems, we developed a scaffold-free 3-dimensional (3D) skin substitute containing vascular networks that combine dermal fibroblasts, endothelial cells, and epidermal keratinocytes based on our layer-by-layer cell coating technique. We transplanted the pre-vascularized 3D skin substitutes onto full-thickness skin defects on severe combined immunodeficiency mice to assess their integration with the host tissue and effects on wound healing. We used non-vascularized 3D skin substitutes as a control. Vessels containing red blood cells were evident in the non-vascularized control by day 14. However, blood perfusion of the human-derived vasculature could be detected within 7 days of grafting. Moreover, the pre-vascularized 3D skin substitutes had high graft survival and their epidermal layers were progressively replaced by mouse epidermis. We propose that a novel dermo-epidermal 3D skin substitute containing blood vessels can promote efficient reconstruction of full-thickness skin defects.
Highlights
Skin defects caused by severe burns, trauma, or non-healing chronic wounds are common and cause clinical problems
Our group recently developed a method for the rapid construction of multicellular stratified 3D tissues by cell surface coating with a nanometer-scale extracellular matrix (ECM) film composed of fibronectin and gelatin (FN-G) using layer-by-layer (LbL) assembly[11,12]
Cells were cocultured at high density (>1 × 107 cells/cm2) to construct scaffold-free 3D skin substitutes
Summary
Skin defects caused by severe burns, trauma, or non-healing chronic wounds are common and cause clinical problems. Sufficient oxygen and nutrition supply and wound infection prevention are critical to the healing process These factors rely on vascularization, which is a key process in skin tissue engineering that determines the biological function of artificial skin grafts. Our group recently developed a method for the rapid construction of multicellular stratified 3D tissues by cell surface coating with a nanometer-scale extracellular matrix (ECM) film composed of fibronectin and gelatin (FN-G) using layer-by-layer (LbL) assembly[11,12]. This technique enables the creation of 3D constructs without exogenous scaffolds or biomaterials because the ECM film, similar to the natural ECM, promotes cell-to-cell interaction and adhesion. Our study provides that pre-vascularized LbL 3D skin be a promising substitute for the clinical applications in the future
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