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StrataGraft Skin Substitute Is Well-tolerated and Is Not Acutely Immunogenic in Patients With Traumatic Wounds: Results From a Prospective, Randomized, Controlled Dose Escalation Trial

Centanni, John M. MS*; Straseski, Joely A. PhD; Wicks, April BS*; Hank, Jacquelyn A. PhD; Rasmussen, Cathy A. PhD*,†; Lokuta, Mary A. PhD*; Schurr, Michael J. MD§; Foster, Kevin N. MD; Faucher, Lee D. MD§; Caruso, Daniel M. MD; Comer, Allen R. PhD*; Allen-Hoffmann, B. Lynn PhD*,†

doi: 10.1097/SLA.0b013e318210f3bd
Randomized Controlled Trial

Objective: The goal of this study was to assess the immunogenicity and antigenicity of StrataGraft skin tissue in a randomized phase I/II clinical trial for the temporary management of full-thickness skin loss.

Background: StrataGraft skin tissue consists of a dermal equivalent containing human dermal fibroblasts and a fully stratified, biologically active epidermis derived from Near-diploid Immortalized Keratinocyte S (NIKS) cells, a pathogen-free, long-lived, consistent, human keratinocyte progenitor.

Methods: Traumatic skin wounds often require temporary allograft coverage to stabilize the wound bed until autografting is possible. StrataGraft and cadaveric allograft were placed side by side on 15 patients with full-thickness skin defects for 1 week before autografting. Allografts were removed from the wound bed and examined for allogeneic immune responses. Immunohistochemistry and indirect immunofluorescence were used to assess tissue structure and cellular composition of allografts. In vitro lymphocyte proliferation assays, chromium-release assays, and development of antibodies were used to examine allogeneic responses.

Results: One week after patient exposure to allografts, there were no differences in the numbers of T or B lymphocytes or Langerhans cells present in StrataGraft skin substitute compared to cadaver allograft, the standard of care. Importantly, exposure to StrataGraft skin substitute did not induce the proliferation of patient peripheral blood mononuclear cells to NIKS keratinocytes or enhance cell-mediated lysis of NIKS keratinocytes in vitro. Similarly, no evidence of antibody generation targeted to the NIKS keratinocytes was seen.

Conclusions: These findings indicate that StrataGraft tissue is well-tolerated and not acutely immunogenic in patients with traumatic skin wounds. Notably, exposure to StrataGraft did not increase patient sensitivity toward or elicit immune responses against the NIKS keratinocytes. We envision that this novel skin tissue technology will be widely used to facilitate the healing of traumatic cutaneous wounds.

This study was registered at www.clinicaltrials.gov (NCT00618839).

Supplemental digital content is available in the text.StrataGraft skin substitute was evaluated in a randomized phase I/II clinical trial that included assessments of the immunological responses of patients to this novel biological skin substitute. There was neither acute inflammatory infiltrate nor any evidence of increased patient sensitivity to the cellular components of the skin substitute. These findings indicate that StrataGraft tissue is well-tolerated and not acutely immunogenic in patients with traumatic skin wounds.

*Stratatech Corporation, Madison, WI.

Departments of Pathology and Laboratory Medicine.

Human Oncology.

§Surgery, University of Wisconsin-Madison, Madison.

Arizona Burn Center at Maricopa Medical Center, Phoenix.

Reprints: B. Lynn Allen-Hoffmann, PhD, University of Wisconsin–Madison, 5605 Medical Sciences Center, 1300 University Avenue, Madison, WI 53706. E-mail: blallenh@wisc.edu.

All authors contributed to the manuscript preparation and gave final approval of the manuscript. Additional responsibilities included the following: J.M.C. contributed to the trial design and was responsible for its oversight, functioned as the clinical liaison, assisted with sample collection, data compilation, and data interpretation. J.A.S. was responsible for the experimental design, conduct, and interpretation of the in vitro data. A.W. was responsible for the management and capture of clinical data. J.A.H. was responsible for the design, conduct and analysis of the in vitro proliferation and cytotoxicity data. C.A.R. was responsible for the conduct and capture of the clinical immunofluorescent data and contributed to the manuscript preparation. M.A.L. was responsible for data analysis and interpretation and manuscript preparation. M.J.S. was the lead clinical investigator who contributed to the trial design, patient enrollment, patient treatment, sample collection, and data interpretation. K.N.F. was responsible for enrolling and treating patients, sample collection, and data acquisition. L.D.F. was responsible for enrolling and treating patients, sample collection and data acquisition. D.M.C. was responsible for enrolling and treating patients, sample collection and data acquisition. A.R.C. was Principal Investigator on the NIH SBIR project that partially funded the clinical trial. As such, Dr Comer was involved in the design of the clinical study, and analysis and interpretation of clinical data from the study. Dr Comer was responsible for interactions with the data and safety monitoring board for this study. B.L.A.-H. was responsible for the overall design and management of the clinical study.

Supported by the following grants: Howard Hughes Medical Institute (M.J.S. and L.A.H.), Stratatech Corporation University of Wisconsin Department of Surgery (M.J.S.), NIH/NIAMS R43-AR47499 (A.R.C.), NIH/NHLBI R01-HL74284 (L.A.H.), NIH/NIAMS R41-AR050349 (L.A.H.), NIH/NIAMS R42-AR050349 (L.A.H.), NIH/NIAMS R44-AR47499 translational clinical grant (A.R.C.).

The studies described within this article were sponsored by Stratatech Corporation, Madison, WI. Please note this research was also funded in part by Howard Hughes Medical Institute, University of Wisconsin Department of Surgery, National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and National Heart, Lung, and Blood Institute (NHLBI).

The authors J.M.C. and J.A.S. contributed equally to the manuscript.

Joely A. Straseski, Jacquelyn A. Hank, Michael J. Schurr, Kevin N. Foster, Lee D. Faucher, and Daniel M. Caruso have no commercial associations that might pose a conflict of interest.

Cathy A. Rasmussen and Mary A. Lokuta are employees of Stratatech Corporation, Madison, WI. John M. Centanni and April Wicks were employed by Stratatech Corporation, Madison, WI, during their contribution to this work.

B. Lynn Allen-Hoffmann, PhD, is the founder of Stratatech Corporation, Madison, WI.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.annalsofsurgery.com).

© 2011 Lippincott Williams & Wilkins, Inc.