Bioengineered smart trilayer skin tissue substitute for efficient deep wound healing

Skin substitutes for deep wound healing require meticulous designing and fabrication to ensure proper structural and functional regeneration of the tissue. Range of physical and mechanical properties conducive for regeneration of different layers of skin is a prerequisite of an ideal scaffold. However, single or bilayer substitutes, lacking this feature, fail to heal full thickness wound. Complete scar free regeneration of skin is still a big challenge. This study reports fabrication of a trilayer scaffold, from biodegradable polymers that can provide the right ambience for simultaneous regeneration of all the three layers of skin. The scaffold was developed through optimization of different fabrication techniques, namely, casting, electrospinning and lyophilisation, for obtaining a tailored trilayer structure. It has mechanical strength similar to skin layers, can maintain a porosity-gradient and provides microenvironments suitable for simultaneous regeneration of epidermis, dermis and hypodermis. A co-culture model, of keratinocytes and dermal fibroblasts, confirms the efficiency of the scaffold in supporting proliferation and differentiation of different types of cells, into organized tissue. The scaffold showed improved and expedited wound healing in-vivo. Taken together, these compelling evidences successfully established the engineered trilayer scaffold as a promising template for skin tissue regeneration in case of deep wound.