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Reconstruction of a Calvarial Wound Complicated by Infection

Comparing the Effects of Biopatterned Bone Morphogenetic Protein 2 and Vascular Endothelial Growth Factor

Brooker, Jack E., MB, BChir*; Camison, Liliana B., MD*,†; Bykowski, Michael R., MD*,†; Hurley, Ethan T., BA*; Yerneni, Saigopalakrishna S., BS; Campbell, Phil G., PhD‡,§; Weiss, Lee E., PhD‡,||; Mooney, Mark P., PhD*,¶; Cray, James, PhD#; Gilbert, James R., PhD*; Cooper, Gregory M., PhD*; Losee, Joseph E., MD*,†,**

doi: 10.1097/SCS.0000000000004779
Scientific Foundations

Bone morphogenetic protein 2 (BMP2) bioprinted on biological matrix induces osseous regeneration in large calvarial defects in rabbits, both uncomplicated and scarred. Healing in unfavorable defects scarred from previous infection is decreased due in part to the lack of vascularity. This impedes the access of mesenchymal stem cells, key to osseous regeneration and the efficacy of BMP2, to the wound bed. The authors hypothesized that bioprinted vascular endothelial growth factor (VEGF) would augment the osseous regeneration achieved with low dose biopatterned BMP2 alone. Thirteen New Zealand white rabbits underwent subtotal calvariectomy using a dental cutting burr. Care was taken to preserve the underlying dura. A 15 mm × 15 mm flap of bone was cut away and incubated in a 1 × 108 cfu/mL planktonic solution of S aureus before reimplantation. After 2 weeks of subsequent infection the flap was removed and the surgical wound debrided followed by 10 days of antibiotic treatment. On postoperative day 42 the calvarial defects were treated with acellular dermal matrix bioprinted with nothing (control), VEGF, BMP2, BMP2/VEGF combined. Bone growth was analyzed with serial CT and postmortem histology. Defects treated with BMP2 (BMP2 alone and BMP2/VEGF combination) showed significantly greater healing than control and VEGF treated defect (P < 0.5). Vascular endothelial growth factor treated defect demonstrated less healing than control and VEGF/BMP2 combination treatments achieved less healing than BMP2 alone though these differences were nonsignificant. Low dose BMP2-patterned acellular dermal matrix improves healing of scarred calvarial defects. Vascular endothelial growth factor at the doses applied in this study failed to increase healing.

*Department of Plastic Surgery, University of Pittsburgh

University of Pittsburgh Medical Center

Department of Biomedical Engineering

§Engineering Research Accelerator

||The Robotics Institute, Carnegie Mellon University

Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA

#College of Dental Medicine, Medical University of South Carolina, Charleston, SC

**Pediatric Plastic Surgery, Childrens Hospital of Pittsburgh of UMPC, Pittsburgh, PA.

Address correspondence and reprint requests to Joseph E. Losee, MD, 4401 Penn Avenue, Faculty Pavilion, 7th Floor, Suite 7104, Pittsburgh, PA 15224; E-mail: joseph.losee@chp.edu

Received 25 January, 2018

Accepted 15 May, 2018

This project was funded in full through the Armed Forces Institute of Regenerative Medicine (AFIRM) of the United States Department of Defense. Award number: W81XWH-14–2-0004

The authors report no conflicts of interest.

© 2019 by Mutaz B. Habal, MD.