Influence of fibrin matrices and their released factors on epidermal substitute phenotype and engraftment

J Tissue Eng Regen Med. 2019 Aug;13(8):1362-1374. doi: 10.1002/term.2879. Epub 2019 Jun 14.

Abstract

Cultured epithelial autografts (CEAs) represent a life-saving surgical technique for full-thickness skin burns covering more than 60% total body surface area. However, CEAs present numerous drawbacks leading to heavy cosmetic and functional sequelae. In our previous study, we showed that human plasma-based fibrin matrices (hPBM) could improve the reparative potential of CEAs. Therefore, in the present work, we sought to investigate the role of hPBM compared with fibrin from purified fibrinogen (FPF) or plastic support on epidermal substitute formation and engraftment. The use of hPBM for epidermal substitute culture improved keratinocyte migration, proliferation, and epidermal substitute organization to a better extent than FPF in vitro. Both fibrin matrices favored greater dermal-epidermal junction protein deposition and prevented their degradation. Keratinocyte differentiation was also decreased using both fibrin matrices. Basement membrane protein deposition was mainly influenced by matrix whereas growth factors released from fibrin especially by hPBM were shown to enhance in vitro keratinocyte migration, proliferation, and epidermal substitute organization. Ultimately, epidermal substitutes grown on hPBM displayed better engraftment rates than those cultured on FPF or on plastic support in a NOD-SCID model of acute wound with the formation of a functional dermal-epidermal junction. Together, these results show the positive impact of fibrin matrices and their released growth factor on epidermal substitute phenotype and grafting efficiency. Fibrin matrices, and especially hPBM, may therefore be of interest to favor the treatment of full-thickness burn patients.

Keywords: cultured epidermal autograft; fibrin matrices; growth factors; severe burn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Basement Membrane / drug effects
  • Basement Membrane / metabolism
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Epidermis / drug effects*
  • Epidermis / ultrastructure
  • Female
  • Fibrin / pharmacology*
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Membrane Proteins / metabolism
  • Mice, Inbred NOD
  • Mice, SCID
  • Phenotype
  • Skin Transplantation*
  • Skin, Artificial*
  • Tissue Engineering

Substances

  • Membrane Proteins
  • Fibrin