Abstract: A Novel Oxysterol Analogue Promotes in Vitro and in Vivo Bone Regeneration (Plastic Surgery 2014)

Saturday, October 11, 2014: 10:20 AM

Reza Jarrahy, MD , UCLA Health, Los Angeles, CA

Akishige Hokugo, DDS PhD , Plastic and Reconstructive Surgery, University of California, Los Angeles, Los Angeles, CA

Andrew Li, MD , Plastic and Reconstructive Surgery, University of California, Los Angeles, Los Angeles, CA

Luis ANDRES Segovia, MD , Plastic Surgery, UCLA, Los Angeles, CA

Introduction

The repair of complex craniofacial defects poses significant reconstructive challenges. Current methods employing autologous bone grafts or alloplastic implants are fraught with complications. Tissue engineering approaches using bone morphogenetic proteins (BMPs) are associated with adverse side effects and exorbitant costs. Here we investigate a novel molecule with significant osteogenic potential. We examined the impact of Oxy133, a novel oxysterol analogue, on in vitro and in vivo osteogenic differentiation of rabbit bone marrow stromal cells (BMSCs).

Methods

Rabbit BMSCs were isolated, cultured, and treated with control media or varying concentrations of Oxy133 or BMP-2. In vitro osteogenic differentiation was assessed via alkaline phosphatase (ALP) assay, quantitative real-time PCR of osteogenic genes, and mineralization assays. In vivo activity was measured by healing of critical-sized rabbit calvarial defects that were treated with collagen sponge/inert control vehicle, collagen sponge/Oxy133, collagen sponge/BMP-2, or no treatment. The calvarium was harvested after seven weeks for histologic and radiographic analysis.

Results

Rabbit BMSCs treated with Oxy133 demonstrated increased ALP activity, up-regulation of osteogenic gene expression, and increased mineralization of cultures compared to controls. Oxy133-treated cells demonstrated osteogenic differentiation with an efficacy similar to that of cells treated with BMP-2 in vitro. Similar to animals treated with BMP-2, critical-sized rabbit calvarial defects showed complete bone regeneration when treated with collagen sponges combined with Oxy133.

Conclusions

Oxy133 induces osteogenic differentiation in rabbit BMSCs as effectively as BMP-2 in both in vitro and in vivo models. Oxysterols may therefore represent a viable alternative to BMP-2 in bone tissue engineering paradigms. Its application to the design of a clinically viable, safe, and cost effective bone graft substitute warrants further study.

25311 A Novel Oxysterol Analogue Promotes in Vitro and in Vivo Bone Regeneration