Porcine Wound Healing in Full-Thickness Skin Defects Using Integra™ with and Without Fibrin Glue with Keratinocytes

Abstract

It appears there is an acceleration of early phase (day 7 to day 21) dermal incorporation with fibrin glue application to the wound bed, perhaps secondary to increased cellular migration. Day 21 appears to be too early to apply cultured keratinocytes either as sheets or aerosolized suspension.

Dermal matrix scaffold engineered with adult mesenchymal stem cells and platelet-rich plasma as a potential tool for tissue repair and regeneration

“…adhesion, ingrowth and survival of the local microenvironment and vascular cells (Stock and Vacanti, 2001; Traphagen and Yelick, 2009; Carnio et al , 2010). Along this line, Integra ® , an artificial dermal matrix that has been shown to provide a suitable wound bed template for vascular and fibrocyte ingrowth as well as for collagen remodelling, has been successfully used to assist the healing of acute and chronic skin defects in several animal models (Ophof et al , 2007; Melendez et al , 2008; Shaterian et al , 2009) as well as in patients with ulcers or burn injuries (Campitiello et al , 2005; Moiemen et al , 2006). The beneficial effects of this substrate have been shown to be dependent on the peculiar microarchitectural (scaffold surface, pore size and interconnectivity) features of the dermal matrix, which are able to guide cell migration and infiltration to new tissue formation.…”

Potentials and limitations of Integra® flowable wound matrix seeded with adipose tissue-derived microvascular fragments

“…The observation window of the dorsal skinfold chamber allowed a continuous access to the implants and, T Später et al Vascularisation of Integra ® Young et al, 1998;Melendez et al, 2008;Danner et al, 2012;Meruane et al, 2012;Killat et al, 2013;Zonari et al, 2015). Recently, we could demonstrate that the seeding of dermal skin substitutes with ad-MVF, which already represent fully functional vessel segments, may be even more effective (Frueh et al, 2017).…”

Can host reaction animal models be used to predict and modulate skin regeneration?

“…In fact, swine full‐thickness skin excisional models have proved useful and reliable tools to evaluate skin regeneration after the grafting of skin tissue‐engineering constructs. In fact, results concerning the involvement of transplanted cells (mostly autologous keratinocytes), acellular matrices and host cells and molecules (Butler and Orgill, ; Druecke et al , ; Jones et al , ; Melendez et al , ; Wood et al , ) obtained with this model were translated to the clinic. Therefore, these and the similarities between porcine and human skin healing counterbalances the high costs and demanding logistics of using this model, and support controversy about the relevance of the results obtained with the different acute skin wound healing rodent models.…”

“…After 6 weeks of implantation in full‐thickness porcine wounds, mononuclear cells (M Φ s and lymphocytes) and giant cells were found in direct contact with the collagen scaffold fibres of Integra. Although no signs of phagocytosis were observed, the number of giant cells was significantly higher than in healthy tissue (Druecke et al , ; Melendez et al , ). This decodes an activation of M Φ s, inducing them to fuse without achieving the phagocytosis step.…”

“…The improvement of scarless skin healing was also associated with beneficial crosstalk between the transplanted keratinocytes and host fibroblasts (Melendez et al , ). In fact, autologous keratinocytes in combination with Integra (R) were shown to enhance the epithelialization of porcine full‐thickness wounds (Jones et al , ; Melendez et al , ; Wood et al , ) and seemed to influence the progression of the inflammatory reaction towards a more remodelling‐prone response.…”