Electrospun poly(hydroxybutyrate) scaffolds promote engraftment of human skin equivalents via macrophage M2 polarization and angiogenesis

J Tissue Eng Regen Med. 2018 Feb;12(2):e983-e994. doi: 10.1002/term.2420. Epub 2017 Jun 4.

Abstract

Human dermo-epidermal skin equivalents (DE) comprising in vitro expanded autologous keratinocytes and fibroblasts are a good option for massive burn treatment. However, the lengthy expansion time required to obtain sufficient surface to cover an extensive burn together with the challenging surgical procedure limits their clinical use. The integration of DE and biodegradable scaffolds has been proposed in an effort to enhance their mechanical properties. Here, it is shown that poly(hydroxybutyrate) electrospun scaffolds (PHB) present good biocompatibility both in vitro and in vivo and are superior to poly-ε-caprolactone electrospun scaffolds as a substrate for skin reconstruction. Implantation of PHB scaffolds in healthy rats polarized macrophages to an M2-type that promoted constructive in vivo remodelling. Moreover, implantation of DE-PHB composites in a NOD/SCID mouse xenograft model resulted in engraftment accompanied by an increase in angiogenesis that favoured the survival of the human graft. Thus, PHB scaffolds are an attractive substrate for further exploration in skin reconstruction procedures, probably due in part to their greater angiogenic and M2 macrophage polarization properties. Copyright © 2017 John Wiley & Sons, Ltd.

Keywords: electrospinning; human skin xenograft; poly(hydroxybutyrate); skin equivalents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Cell Differentiation / drug effects
  • Cell Polarity* / drug effects
  • Cell Proliferation / drug effects
  • Dermis / cytology
  • Dermis / ultrastructure
  • Epidermis / ultrastructure
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Hydroxybutyrates / pharmacology*
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice, Inbred NOD
  • Mice, SCID
  • Neovascularization, Physiologic* / drug effects
  • Polymers / chemistry
  • Prohibitins
  • Rats, Wistar
  • Skin Transplantation
  • Skin, Artificial*
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry*

Substances

  • Biocompatible Materials
  • Hydroxybutyrates
  • PHB protein, human
  • Phb protein, rat
  • Polymers
  • Prohibitins