Pre-vascularized dermis model for fast and functional anastomosis with host vasculature

Biomaterials. 2019 Feb:192:159-170. doi: 10.1016/j.biomaterials.2018.11.018. Epub 2018 Nov 14.

Abstract

Skin engineering for clinical applications has gained numerous advances, however, most of the available dermis substitutes are exogenous matrices acting for a limited time. Indeed, after implantation these matrices need to be colonized by host cells such as fibroblast and endothelial cells which respectively produce their own extracellular matrix and set a vascular network within the construct. These steps are essential to guarantee implant efficacy, but they may require a long time depending on tissue dimension and lesion severity. Here we show the pre-vascularization process of a dermis equivalent featured by an endogenous matrix produced by human dermal fibroblasts. In this environment, endothelial cells were able to develop mature capillary-like-structures (CLS) as demonstrated by both the inner lumen and the positivity for alpha-SMA, laminin and collagen. The pre-vascularized dermis model (PVD) so obtained had a human matrix populated by fibroblasts as well as a complex capillary network making the construct ready to be implanted. These features make the graft very easy to handle during the surgery. In vivo results showed that 7 days after implantation CLS effectively anastomosed with host vessels. Therefore we argue that the proposed PVD may represent a new class of dermis substitute of strong clinical interest.

Keywords: Anastomosis; Capillary like structures; Dermis substitutes; Endogenous matrix; Skin engineering; Vascularization.

MeSH terms

  • Animals
  • Cells, Cultured
  • Dermis / blood supply*
  • Endothelial Cells / cytology
  • Extracellular Matrix / chemistry
  • Fibroblasts / cytology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Neovascularization, Physiologic*
  • Skin, Artificial*
  • Tissue Engineering* / methods
  • Wound Healing