Skin tissue engineering requires a multidisciplinary effort, reflecting the
complexity of the organ that it attempts to replace after loss due to injury, trauma or as
a consequence of diseases. Skin substitution aims to achieve complete closure of the
existing defect and restoration of the normal function of the tissue. The major challenge
faced whilst attempting to achieve such outcomes is successfully recapitulating the
complex biology, chemistry and mechanical environments within native skin. Although
major advances have been made to include biological entities (cells, biomolecules,
small molecules) into engineered substrates to promote biological responses, the role
that the substrate itself provides is often overlooked. In this chapter, we consider what
might be required so that successful skin substitution post-trauma can be routinely
achieved. This will require that researchers from different disciplines collaborate to
ensure that not only should the cell types and matrices be carefully chosen, but in
parallel, the resultant mechanical parameters need to be considered in the design
process. We postulate that an engineering approach is required to recapitulate the skin
by driving native healing pathways, ultimately creating a system where the synergistic
effects are greater than simply the sum of its parts; where each partial component
reflects various aspects of the human biology (cells, annexal structures, etc.), chemistry
(materials, gradients, etc.) and physics (mechanics, etc.).
Keywords: Regeneration, Skin, Skin substitutes, Tissue engineering, Wound repair
