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bioRxiv · 10.1101/2020.06.15.152140

Demonstration of re-epithelialization in a bioprinted human skin equivalent wound model

Poblete Jara, C.·Catarino, C. M.·Lei, Y.·Velloso, L. A.·Karande, P.·Velander, W. H.·P Araujo, E.
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Abstract

ObjectiveThe development of an in vitro platform for modeling human skin injury and the re-epithelization process. ApproachA fibrin provisional matrix (FPM) was installed into a wound facsimile of a bioprinted human skin equivalent (HSE). A mixture of plasma-derived fibrinogen-containing factor XIII, fibronectin, thrombin, and macrophages (an FPM "bioink") was extruded into the wound site. The surrounding in vitro tissue culture became a source of keratinocytes to achieve wound closure by a re-epithelialization process signaled by the FPM. ResultsAn in vitro analog of wound closure and re-epithelialization by keratinocytes occurred over the FPM after a normal migration initiation at 3 days. InnovationA physiologic mixture of macrophage/fibrinogen/fibronectin that supports macrophage differentiation was applied to a mechanically wounded, bioprinted dermal tissue. We developed a transitional culture medium to mimic the changing microenvironment during the initial phases of wound healing. As a reference, we temporally compared our in vitro model with a murine skin wound healing. ConclusionThis co-culture model was shown to temporally synchronize a re-epithelization process for initiation of keratinocyte migration from a surrounding tissue and the migration process over the top of an FPM. A future study of the analogous subepithelial healing pathway is envisioned using the same in vitro bioprinted tissue study platform for co-culture of keratinocytes, melanocytes, fibroblasts, endothelial cells, and macrophages using more specialized FPMs.

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Poblete Jara, C., Catarino, C. M., Lei, Y., Velloso, L. A., Karande, P., Velander, W. H., P Araujo, E.. 2020-06-16. Demonstration of re-epithelialization in a bioprinted human skin equivalent wound model. https://doi.org/10.1101/2020.06.15.152140

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