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Interleukin-10 Does Not Augment Osseous Regeneration in the Scarred Calvarial Defect Achieved with Low-Dose Biopatterned BMP2

Brooker, Jack E. M.D.; Bykowski, Michael R. M.D.; Camison, Liliana M.D.; Yerneni, Saigopalakrishna M.S.; Campbell, Phil G. Ph.D.; Weiss, Lee Ph.D.; Mooney, Mark P. Ph.D.; Cray, James J. Ph.D.; Cooper, Gregory M. Ph.D.; Losee, Joseph E. M.D.

Plastic and Reconstructive Surgery: June 2019 - Volume 143 - Issue 6 - p 1215e-1223e
doi: 10.1097/PRS.0000000000005640

Background: Large calvarial defects represent a major reconstructive challenge, as they do not heal spontaneously. Infection causes inflammation and scarring, further reducing the healing capacity of the calvaria. Bone morphogenetic protein-2 (BMP2) has been shown to stimulate osteogenesis but has significant side effects in high doses. BMP2 has not been tested in combination with antiinflammatory cytokines such as interleukin-10.

Methods: Sixteen New Zealand White rabbits underwent 15 × 15-mm flap calvarectomies. The flap was incubated in Staphylococcus aureus and replaced, and infection and scarring were allowed to develop. The flap was subsequently removed and the wound débrided. A 15 × 15-mm square of acellular dermal matrix biopatterned with low-dose BMP2, interleukin-10, or a combination was implanted. Computed tomographic scans were taken over 42 days. Rabbits were then killed and histology was performed.

Results: Defects treated with BMP2 showed significantly (p < 0.05) greater osseous regeneration than untreated controls. Interleukin-10 did not significantly augment the healing achieved with BMP2, and interleukin-10 alone did not significantly increase healing compared with controls. Histology showed evidence of bone formation in defects treated with BMP2. Untreated controls and defects treated with interleukin-10 alone showed only fibrous tissue in the defect site.

Conclusions: Low-dose BMP2 delivered directly to the scarred calvarial defect augments bony healing. Interleukin-10 at the dose applied did not significantly augment healing alone or in combination with BMP2. Healing had not finished at 42 days and analysis at later time points or the use of higher doses of BMP2 may yield greater healing.

Pittsburgh, Pa.; and Columbus, Ohio

From the Department of Plastic Surgery, University of Pittsburgh; Biomedical Engineering and Biological Sciences and The Robotics Institute, Carnegie Mellon University; and The Ohio State University College of Medicine.

Received for publication January 29, 2018; accepted October 19, 2018.

Presented at the 60th Annual Meeting of the Ohio Valley Society of Plastic Surgeons, in Pittsburgh, Pennsylvania, June 2 through 4, 2017; the 17th Biennial Congress of the International Society of Craniofacial Surgery, in Cancun, Mexico, October 24 through 28, 2017; the Armed Forces Institute for Regenerative Medicine Investigators Meeting, in Bethesda, Maryland, February 1, 2018.

Disclosure:The authors have no conflicts of interest. No funding was provided for the preparation of this article.

Joseph E. Losee, M.D., University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Faculty Pavilion, 7th Floor, Suite 7104, Pittsburgh, Pa. 15224,

Copyright © 2019 by the American Society of Plastic Surgeons