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

Meuli, Martin M.D.; Hartmann-Fritsch, Fabienne Ph.D.; Hüging, Martina M.D.; Marino, Daniela Ph.D.; Saglini, Monia M.Sc.; Hynes, Sally M.D.; Neuhaus, Kathrin M.D.; Manuel, Edith; Middelkoop, Esther Ph.D.; Reichmann, Ernst Ph.D.; Schiestl, Clemens M.D.

Plastic and Reconstructive Surgery: July 2019 - Volume 144 - Issue 1 - p 188-198
doi: 10.1097/PRS.0000000000005746
Pediatric/Craniofacial: Original Articles
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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 cm2 were bioengineered using autologous keratinocytes and fibroblasts isolated from a patient’s small skin biopsy specimen (4 cm2), 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.

Zurich, Switzerland; and Amsterdam, The Netherlands

From the Pediatric Burn Center, Plastic and Reconstructive Surgery, Children’s Skin Center, the Tissue Biology Research Unit, Department of Surgery, and the Children’s Research Center, University Children’s Hospital Zurich; and the Department of Plastic, Reconstructive and Hand Surgery, VU University Medical Center, Amsterdam Movement Sciences.

Received for publication March 20, 2018; accepted November 16, 2018.

The last two authors contributed equally to this study.

This trial is registered under the name “Phase I Study for Autologous Dermal Substitutes and Dermo-epidermal Skin Substitutes for Treatment of Skin Defects,” ClinicalTrials.gov identification number (https://clinicaltrials.gov/ct2/show/NCT02145130).

Disclosure:M.M., C.S., E.R., D.M., and F.H.-F. are founding members of CUTISS AG, a biotech start up developing the here described cultured autologous dermo-epidermal skin substitute toward manufacturing scale up and commercialization. The other authors have no financial interest to declare in relation to the content of this article.

Ernst Reichmann, Ph.D., Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, August Forel Strasse 7, 8008 Zurich, Switzerland, ernst.reichmann@kispi.uzh.ch

Copyright © 2019 by the American Society of Plastic Surgeons