Creation Of A Bioengineered, Porcine, Full-thickness Skin Graft With A Perfusable Vascular Pedicle
Bernhard J. Jank, MD1, Jeremy Goverman, MD, FACS1, Jacques P. Guyette, PhD1, Jon M. Charest, MS1, Mark Randolph, MAS1, Joshua R. Gershlak, MS2, Glenn R. Gaudette, PhD2, Martin Purschke, PhD1, Emilia Javorsku, MD, MPH1, David A. Leonard, MD1, Curtis L. Cetrulo, Jr., MD, FACS, FAAP1, William G. Austen, Jr., MD, FACS1, Harald C. Ott, MD1.
1Massachusetts General Hospital, Boston, MA, USA, 2Worcester Polytechnic Institute, Worcester, MA, USA.
Current treatments for skin loss result in contracture, scar, and poor function; therefore the creation of an autologous full thickness skin analogue remains of paramount importance. The purpose of this project was to create a full thickness skin analogue by perfusion decellularization of a porcine fasciocutaneous flap.
Fasciocutaneous porcine flaps were harvested and perfusion decellularization performed via vascular pedicle. The resulting matrix was characterized, in-vitro biocompatibility and mechanical testing was performed and regenerative potential was evaluated. Imunological response, biocompatibility, and regenerative potential was assessed using in-vivo models.
Perfusion decellularization removed all cellular components with preservation of ECM proteins in similar composition to native skin (Figure 1). Biaxial testing revealed preserved elastic properties. Immunologic response and biocompatibility assessed via implantation and compared with native xenogenic skin and commercially available dermal substitutes revealed neovascularization and tissue integration was most optimal for our flap. Composition of infiltrating immune cells was similar to sham and resembled inflammatory phase of healing. Implantation into full-thickness skin defects demonstrated optimal tissue integration and skin regeneration without cicatrization.
We have developed a protocol for the generation of a full thickness skin matrix of clinically relevant size, containing a vascular pedicle which can be utilized for perfusion decellularization and ultimately, anastomosis to recipient vascular system after pre-cellularization. We demonstrate formidable regenerative potential and favorable immunological response resulting in optimal tissue integration.
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