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VEGF Does Not Improve BMP-2-Mediated Bone Regeneration in the Complicated Calvarial Defect in Rabbits

Liliana Camison, MD; Michael R. Bykowski, MD; Jack Brooker, MD; Lee Weiss, MD; Phil M. Campbell, PhD; Gregory M. Cooper, PhD; Joseph E. Losee, MD
University of Pittsburgh
2017-02-15

Presenter: Liliana Camison

Affidavit:
Liliana Camison (research fellow) contributed over 50% of the work for this abstract. The abstract co-authors all made significant contributions.

Director Name: Vu Nguyen

Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Craniomaxillofacial

Background: Calvarial defects pose a reconstructive challenge, especially in the setting of infection and subsequent scarring. This hostile environment inhibits bone healing, complicating reconstructive efforts. We aimed to improve bone healing in complicated calvarial defects using inkjet bio-printing of low-dose growth factors (5.5ug BMP-2 and 2.75ug VEGF) in a biologic matrix.

Methods: 15x15mm calvarial defects were created in 14 adult NZW rabbits. The bone graft was inoculated with Staphylococcus aureus and replaced in situ. After a 2-week infection, animals underwent debridement and a 10-day course of antibiotics. Six weeks later, the defect was exposed and treated with an acellular dermal matrix (ADM) construct bio-printed with either: a) BMP-2; b) VEGF; c) BMP-2+VEGF; or d) ADM alone/control. After reconstruction, rabbits underwent CT scans at days 0,14,28 and 42 for evaluation of bone regeneration.

Results: Bone regeneration was significantly higher in the BMP-2 group (10.6%) than controls (0.5%) at day 14. By day 42, bone regeneration in the BMP-2 group (25.6%) was significantly higher than the VEGF only group (9.2%), and higher than in the control (13.1%) and combination (17.48%) groups. There was a trend for lower bone regeneration in the BMP-2+VEGF group compared to BMP-2 alone at all time points, although this did not reach significance.

Conclusions: Microdoses of bio-printed BMP-2 increase bone regeneration 50% above no therapy in scarred calvarial defects. VEGF did not improve bone healing, either alone or combined with BMP-2. Although this not sufficient to be considered a viable reconstruction, a longer time-point might show improved outcomes.

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