VEGF Does Not Improve BMP-2-Mediated Bone Regeneration of Complicated Calvarial Defects in Rabbits
Liliana Camison, MD1, Michael R. Bykowski, MD1, Jack E. Brooker, MD1, Sai G. Yerneni, PhD2, Phil M. Campbell, PhD2, Greg M. Cooper, PhD1, Joseph E. Losee, MD1.
1University of Pittsburgh, Pittsburgh, PA, USA, 2Carnegie Mellon University, Pittsburgh, PA, USA.
BACKGROUND: Complex craniofacial wounds resulting in calvarial defects pose a reconstructive challenge. Bacterial contamination is common and often results in infection, limiting options for primary salvage and secondary reconstruction by inhibiting bone healing and inducing significant scarring. This project aimed to improve bone repair in these complicated calvarial defects through the delivery of low-dose BMP-2 and VEGF in a biologic matrix, using inkjet bio-printing.
METHODS: 15 x 15mm calvarial defects were created in 14 adult NZW rabbits. The bone graft was inoculated with S. aureus and replaced in situ. After a 2-week period of infection, animals underwent debridement and a 10-day course of antibiotics. Six weeks later, the defect was exposed, debrided 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. Histology was performed after euthanasia.
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 BMP-2+VEGF (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 were able to increase bone regeneration by 50% above no therapy in complicated, scarred calvarial defects in rabbits at 6 weeks. However, VEGF did not improve bone healing any further, either alone or combined with BMP-2. Further research along this line is warranted. Longer time-points or increased doses might translate into improved outcomes.
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