Bone Regeneration Device for Compromised Wounds
Abstract
Military personnel are substantially burdened with traumatic bone injury to the extremities, but no ideal therapy is available to regenerate large bone volumes in compromised wounds. These wounds are suboptimal for regeneration because the vascular damage and immune response provoke oxygen deficiency and inflammation, which impair bone growth and drive formation of fibrous tissue. Our technology to accelerate bone healing is an off-the-shelf biologic device that can be loaded with minimally manipulated autologous mesenchymal stem cells (MSCs) at the point-of-care. It consists of the following components: (1) drugs to control the immune response and promote healing, (2) hydrogel carrier to deliver the drugs and to control tissue formation by MSCs, (3) nanoparticles to deliver the drugs over prolonged periods, and (4) porous scaffold to provide mechanical support in large bone defects. These components are assembled in two forms depending on the nature of the bone injury: an injectable hydrogel and an implantable hydrogel infused scaffold. We expect that an injectable device (components 1-3) will be used by first responders to stabilize bone fragments in comminuted fractures, prevent fibrous tissue ingrowth, and rapidly initiate regeneration. We expect that an implantable device (all components) will be used in the operating theater to promote bone formation and minimize non-union when conventional grafts and bone fillers are contraindicated. We will evaluate bone regeneration over time in two bone injury models in swine. We will test the injectable device in a simulated comminuted fractures of the fibula while the implantable device in large fibular bone defects. We will evaluate bone formation and strength, revascularization, and reinnervation, and the local and host immune responses. Approximately 20% of injured combat personnel suffer extremity bone fracture and loss, of which 80% are open compromised wounds with significant tissue loss post-debridement. Our device will minimize the severe morbidity and treatment cost for wounded military personnel and improve their quality of life and return to service. Ultimately, this work will translate to several clinical therapies in the form of pharmacological interventions and therapeutic devices to promote skeletal healing. These will decrease clinical involvedness and impact individual s lives by speeding skeletal healing, diminishing non-union and tissue fibrosis incidence, and reducing multi-surgery procedures.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610793
Entities
People
- Juan M Taboas
Organizations
- United States Army
- University of Pittsburgh