Advances in electrospun skin substitutes

In recent years, nanotechnology has received much attention in regenerative medicine, partly owing to the production of nanoscale structures that mimic the collagen fibrils of the native extracellular matrix. Electrospinning is a widely used technique to produce micro-nanofibers due its versatility, low cost and easy use that has been assuming an increasingly prominent position in the tissue engineering field. Electrospun systems have been especially investigated for wound dressings in skin regeneration given the intrinsic suitability of fibrous structures for that purpose. Several efforts have been made to combine distinct design strategies, synthetic and/or natural materials, fiber orientations and incorporation of substances (e.g. drugs, peptides, growth factors or other biomolecules) to develop an optimized electrospun wound dressing mimicking the native skin. This paper presents a comprehensive review on current and advanced electrospinning strategies for skin regeneration. Recent advances have been mainly focused on the materials used rather than on sophisticated fabrication strategies to generate biomimetic and complex constructs that resemble the mechanical and structural properties of the skin. The technological limitations of conventional strategies, such as random, aligned and core-shell technologies, and their poor mimicking of the native tissue are discussed. Advanced strategies, such as hybrid structures, cell and in situ electrospinning, are highlighted in the way they may contribute to circumvent the limitations of conventional strategies, through the combination of different technologies and approaches. The main research challenges and future trends of electrospinning for skin regeneration are discussed in the light of in vitro but mainly in vivo evidence.