Oxy133, A Novel Osteogenic Agent, Promotes Bone Regeneration In The Rat Alveolar Cleft Model
Reena Bakshi, MD1, Akishige Hokugo, DDS, PhD1, Situo Zhou, MD1, Frank Stappenbeck, PhD2, Farhad Parhami, PhD2, Reza Jarrahy, MD1.
1UCLA, Los Angeles, CA, USA, 2MAX BioPharma, Los Angeles, CA, USA.
Bone morphogenetic proteins (BMPs) play a central role in the development of bone regeneration therapies in cleft surgery. However, the high cost and side effect profile, including significant inflammation, limits its broad application. Osteogenic oxysterols--naturally occurring products of cholesterol oxidation with osteogenic properties--are a promising alternative. In this study, we studied the impact of Oxy133, a specific oxysterol isoform, on in vivo bone regeneration in a rodent rat cleft model.
Critical-sized alveolar defects were generated in Sprague-Dawley rats. Defects were reconstructed with either no treatment, a collagen sponge without additive, a collagen sponge containing BMP-2, or a collagen sponge containing 1, 10, or 20 mg of Oxy133. Alveolar segments were harvested after 8 weeks for histologic and radiographic analyses. Peripheral blood was collected at the various time points before euthanasia to assess inflammatory markers.
Defects treated with BMP-2 and 20mg of Oxy133 showed the greatest amount of new bone formation. Treatment with the lower doses Oxy 133 demonstrated significant increases in bone formation compared with untreated defects. Histologically, bone regeneration was characterized by architecturally mature bone and near complete bridging of the alveolar defect. Animals treated with Oxy133 showed no evidence of upregulation of local or systemic inflammatory responses.
Oxy 133 is able to promote bone regeneration in an alveolar cleft model. It has the capacity to heal alveolar defects without a severe immune response. These observations demonstrate that Oxy133 has strong clinical potential as a viable alternative to BMP-2 in bone tissue engineering.
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