Editors' ChoiceTissue Engineering

Skin Substitutes: Already Done, or Just the Beginning?

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Science Translational Medicine  03 Apr 2013:
Vol. 5, Issue 179, pp. 179ec54
DOI: 10.1126/scitranslmed.3006202

It has been almost 30 years since the first cell-based skin substitute became commercially available. This was a paradigm-shifting moment and an excellent example of translation, moving from a vision to a product that became available to many patients. Reminiscent of that early success story, today one may think that skin substitutes are something of the past—a solved problem. Michael and colleagues exemplify a new era of skin tissue engineering by using laser-assisted bioprinting to create skin constructs consisting of 40 layers of human cells on a collagen matrix.

Major burns require large grafts that are able to reproduce the native skin’s protective, storage, and temperature-control functions. The authors reasoned that achieving such properties would entail three-dimensional (3D) patterning of the different cell types and extracellular matrix (ECM) components that form skin in a 3D configuration that closely mimics the skin’s morphology. Michael et al. used a laser to print 20 layers of fibroblasts and 20 layers of keratinocytes on a collagen (ECM) matrix. These constructs were implanted by using a dorsal skin-fold chamber in nude mice. After 11 days, the grafts integrated with the neighboring tissue. Analysis of the excised grafts revealed a dense, stratified, skin-like tissue that was rich in keratinocytes (epidermis) topping layers of elongated fibroblasts. These fibroblasts were also able to produce collagen (dermis). Small blood vessels could be found in the skin constructs as well.

The skin substitute was grafted into mice, so it is currently limited by its small size (6-mm disc). This would need to be scaled up to accommodate major burn injuries in humans. The authors also did not see any large blood vessels or differentiation of most keratinocytes within the graft, suggesting that longer implantation times may be needed in future studies. Still, the study by Michael et al. demonstrates that bioprinting techniques show great potential in easing the path to the manufacture of large, but precise, 3D living structures such as skin. For decades, this has been one of the bottlenecks of turning early lab-scale successes in tissue engineering into products for masses.

S. Michael et al., Tissue engineered skin substitutes created by laser-assisted bioprinting form skin-like structures in the dorsal skin fold chamber in mice. PLoS One 8, e57741 (2013). [Full Text]

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