Anti-Vegf Antibody Delivered Locally Reduces Bony Bar Formation Following Physeal Injury In Rats

Physeal injuries can result in the formation of a "bony bar" which can lead to bone growth arrest and deformities in children. Vascular endothelial growth factor (VEGF) has been shown to play a role in bony bar formation, making it a potential target to inhibit bony repair tissue after physeal injury. The goal of this study was to investigate whether the local delivery of anti-VEGF antibody (alpha-VEGF; 7.5 mu g) from alginate:chitosan hydrogels to the tibial physeal injury site in rats prevents bony bar formation. We tested the effects of quick or delayed delivery of alpha-VEGF using both 90:10 and 50:50 ratio alginate:chitosan hydrogels, respectively. Male and female 6-week-old Sprague-Dawley rats received a tibial physeal injury and the injured site injected with alginate-chitosan hydrogels: (1) 90:10 (Quick Release); (2) 90:10 + alpha-VEGF (Quick Release + alpha-VEGF); (3) 50:50 (Slow Release); (4) 50:50 + alpha-VEGF (Slow Release + alpha-VEGF); or (5) Untreated. At 2, 4, and 24 weeks postinjury, animals were euthanized and tibiae assessed for bony bar and vessel formation, repair tissue type, and limb lengthening. Our results indicate that Quick Release + alpha-VEGF reduced bony bar and vessel formation, while also increasing cartilage repair tissue. Further, the quick release of alpha-VEGF neither affected limb lengthening nor caused deleterious side-effects in the adjacent, uninjured physis. This alpha-VEGF treatment, which inhibits bony bar formation without interfering with normal bone elongation, could have positive implications for children suffering from physeal injuries.