Posted January 8, 2013
Elizabeth A. Olmsted-Davis, Ph.D., Baylor College of Medicine, Houston, Texas
Spinal conditions that lead to spine instability and bone degeneration are treated with spine fusion that requires invasive, painful surgery that involves stripping of the musculature, autologous bone grafts, and insertion of metal at the site of injury. Spinal fusion from these procedures can take as long as a year to achieve. Moreover, approximately 30% of the surgeries fail to produce spinal fusion due to inability of the fusion mass to adequately form and integrate with the pre-existing skeletal bone, which leads to significant pain.
Previous studies of human genetic disease have demonstrated that bone morphogenetic protein 2 (BMP2), a protein that plays an important role in the development of bone and cartilage, has the potential to rapidly form bone that can fuse into the skeleton. With support from a Fiscal Year 2006 Peer Reviewed Medical Research Program Advanced Technology: Product/Technology Down-Selection or Optimization Award, Dr. Elizabeth Olmsted-Davis and her colleagues Dr. Alan Davis and Dr. Jennifer West sought to test the hypothesis that sustained delivery of endogenously produced BMP2 at a target site could lead to rapid bone formation that would be capable of fusing with skeletal bone. This would provide a safe, efficacious system for inducing spine fusion that will eliminate the need of invasive surgery.
Dr. Olmsted-Davis and her team injected BMP2-producing cells encapsulated in a polyethylene diacrylate hydrogel (PEGDA) into the desired site in rodents, which led to rapid spinal fusions within 2 weeks. This non-surgical procedure is unique in several ways: (1) the BMP2 is endogenously produced in human cells at the specific location to mimic normal physiological levels, thus avoiding many of the adverse effects associated with high-dose delivery; (2) the BMP2-producing cells are encapsulated in hydrogels that permit free diffusion of BMP2, but prevents the cells from migrating away from the target location; (3) the encapsulation prevents immune detection and clearance of the cells and thus does not require cells from individual patients to be harvested and generated, but rather a single (allogenic) cell line can be used for manufacturing; (4) the microspheres can be injected multiple times to "tune" bone formation and spine fusion; (5) the materials can be specifically degraded during normal bone remodeling; (6) the cell line carries a "safety switch" that will allow physicians to instantly turn off bone formation, if needed, by delivery of a Food and Drug Administration (FDA)-approved small molecule; and (7) the osteoinductive microspheres can be cryopreserved and maintain efficacy, so that the system can be easily distributed for clinical use. Moreover, the system has significant versatility and has the potential to be useful in limb salvage and regeneration. Based on these promising results, Dr. Olmsted-Davis and her colleagues plan to refine this technique and generate preclinical data for FDA approval for use in humans.
Olabisi RM, Lazard Z, Heggeness M, Moran KM, Hipp JA, Dewan A, Davis AR, West JL, and Olmsted-Davis EA. 2011. An injectable method for spine fusion. Spine J 11(6):545-546.
Hsu CW, Olabisi RM, Olmsted-Davis EA, Davis AR, and West JL. 2011. Cathepsin K-sensitive poly(ethylene glycol) hydrogels for degradation in response to bone resorption. J Biomed Mater Res A 98(1):53-62.
Olabisi RM, Lazard ZW, Hall MA, Kwon SK, Sevick-Muraca EM, Hipp JA, Davis AR, Olmsted-Davis EA, and West JL. 2010. Hydrogel microsphere encapsulation of a cell-based gene therapy system increases cell survival of injected cells, transgene expression, and bone volume in a model of heterotopic ossification. Tissue Eng Part A 16(12):3727-3736.