Tethered Recombinant Human BMP2 Delivered with Beta-Tricalcium Phosphate Nanoparticles for the Treatment of Open Tibial Fracture
Abstract
Our proposal directly addresses the two most common injuries that Service members suffer during both combat and peacetime operations, namely, traumatic bone injuries from explosive devices and back pain due to spinal disc degeneration from years of physical stress. The ultimate goal of our work is to maximize the ability of Service members to return to duty following traumatic bone injury or spinal disc degeneration. Orthopedic device companies are not motivated to address military injury because of competing civilian markets, which focus on disease and not trauma. In contrast, our work specifically targets these types of traumatic and stress-related injuries, and we propose to develop the first orthopedic product that is specifically targeted at military injury. By far the most common combat injury is to the extremities, accounting for over 70% all injuries. Ten to fifteen percent of these injuries result in non-union or delayed union. Compared with patients with a healed tibial fracture, those with a non-union have poorer physical and mental function and more post-traumatic psychological distress. Currently there are no therapies available to effectively treat non-union tibial fractures. Often, limbs with untreatable non-healing in the bone must be amputated. Our approach may save limbs from amputation by allowing bone to regrow over longer distances. This is a key goal of our proposal. Bone morphogenetic protein-2 (BMP2) is the most potent bone-inducing agent identified to date. However, its use has suffered setbacks due to serious safety concerns. With the support of a 2011 Peer Reviewed Orthopedic Research Program grant and our ongoing 2015 Joint Warfighter Medical Research Program contract, we developed a proprietary variant of bone morphogenetic protein 2 (BMP2) called tBMP2 that binds very tightly to ceramic materials. Using this technology, we have created porous ceramic implants that are surface coated with tBMP2 that retains the potent bone-forming protein at the implant site. We used this technology to develop our lead product called Osteo-Adapt BVF, which is a fully synthetic bone graft material composed of tBMP2 loaded at very tunable doses on Vitoss®, a U.S. Food and Drug Administration (FDA) 510(K) cleared device used for bone defects. We validated our tBMP2 therapeutic in models of long-bone defects in Investigational New Device (IND)-enabling rodent, rabbit, and goat models. In our IND-enabling rat large defect study, we demonstrated superior safety and efficacy of Osteo-Adapt BVF to heal bone fractures compared to InFuse, the current leading commercially available rhBMP2 product made by Medtronic. Osteo-Adapt BVF beat Medtronic’s InFuse on all measures of bone healing. Because the protein (tBMP2) used for long bone repair is the same as is used for the spinal fusion product, this Peer Reviewed Medical Research Program proposal will have a far-reaching impact in another area of great concern for the Department of Veterans Affairs (VA) and the Department of Defense (DoD). The most common injury during peacetime is back pain associated with degenerative disc disease (DDD). More Service members are medically separated for back pain than for any other condition. This non-combat injury accounted for 28% of all medical separations, making it the top condition for medical separation in the military by a wide margin. This comes at a huge cost to the military and to the Service member’s career and family. Current spinal fusion technology to correct DDD carries high risks and is avoided unless absolutely necessary. Our approach will dramatically improve the safety of these procedures by lowering the required dose of bone-forming growth factors and will allow more Service members to safely benefit from this corrective treatment. As a result, many more will to return to duty and remain productive. In this proposal, we focus on the development of the bone repair product, Osteo-Adapt BVF.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010305
Entities
People
- Luis Alvarez
Organizations
- United States Army