A Cultured Autologous Dermo-epidermal Skin Substitute for Full-Thickness Skin Defects: A Phase I, Open, Prospective Clinical Trial in Children

Plast Reconstr Surg. 2019 Jul;144(1):188-198. doi: 10.1097/PRS.0000000000005746.

Abstract

Background: The management of deep partial-thickness and full-thickness skin defects remains a significant challenge. Particularly with massive defects, the current standard treatment, split-thickness skin grafting, is fraught with donor-site limitations and unsatisfactory long-term outcomes. A novel, autologous, bioengineered skin substitute was developed to address this problem.

Methods: To determine whether this skin substitute could safely provide permanent defect coverage, a phase I clinical trial was performed at the University Children's Hospital Zurich. Ten pediatric patients with acute or elective deep partial- or full-thickness skin defects were included. Skin grafts of 49 cm were bioengineered using autologous keratinocytes and fibroblasts isolated from a patient's small skin biopsy specimen (4 cm), incorporated in a collagen hydrogel.

Results: Graft take, epithelialization, infection, adverse events, skin quality, and histology were analyzed. Median graft take at 21 days postoperatively was 78 percent (range, 0 to 100 percent). Healed skin substitutes were stable and skin quality was nearly normal. There were four cases of hematoma leading to partial graft loss. Histology at 3 months revealed a well-stratified epidermis and a dermal compartment comparable to native skin. Mean follow-up duration was 15 months.

Conclusions: In the first clinical application of this novel skin substitute, safe coverage of skin defects was achieved. Safety and efficacy phase II trials comparing the novel skin substitute to split-thickness skin grafts are ongoing.

Clinical question/level of evidence: Therapeutic, IV.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adolescent
  • Bioengineering
  • Burns / surgery*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Dermis / cytology
  • Dermis / transplantation
  • Epidermal Cells / transplantation
  • Epidermis / transplantation
  • Female
  • Fibroblasts / transplantation
  • Humans
  • Infant
  • Keratinocytes / transplantation
  • Male
  • Prospective Studies
  • Skin / injuries*
  • Skin Transplantation / methods*
  • Skin, Artificial*
  • Transplantation, Autologous