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Anti-VEGF antibody delivered locally reduces bony bar formation following physeal injury in rats.

Christopher B EricksonJake P NewsomNathan A FletcherYangyi YuFrancisco Rodriguez FontanShane A WeatherfordNancy Hadley MillerMelissa D KrebsKarin A Payne
Published in: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (2020)
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 (α-VEGF; 7.5 μg) 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 α-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 + α-VEGF (Quick Release + α-VEGF); (3) 50:50 (Slow Release); (4) 50:50 +  α-VEGF (Slow Release +  α-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 + α-VEGF reduced bony bar and vessel formation, while also increasing cartilage repair tissue. Further, the quick release of α-VEGF neither affected limb lengthening nor caused deleterious side-effects in the adjacent, uninjured physis. This α-VEGF treatment, which inhibits bony bar formation without interfering with normal bone elongation, could have positive implications for children suffering from physeal injuries.
Keyphrases
  • vascular endothelial growth factor
  • endothelial cells
  • drug delivery
  • wound healing
  • young adults
  • clinical trial
  • randomized controlled trial
  • mouse model
  • human health
  • replacement therapy
  • preterm birth
  • gestational age