Sustained Release Therapeutic for Extremity Trauma Repair
Abstract
This work directly addresses the topic area of Sustained Release Drug Delivery. We specifically address the following subtopics: (1) Research into techniques for sustained release of drugs in tissue repair applications. (2) Development of a delivery system (including novel Good Manufacturing Practice GMP-grade biomaterials). Our work targets the treatment of traumatic extremity injury with associated bone fracture, which is the most common injury that Service Members suffer during combat. 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. We have developed a variant of BMP2 called AMP2 that binds very tightly to implant materials. Using this technology, we have created resorbable implants that are surface-coated with AMP2 that retain the biologic at the implant site over the extended period of time required to achieve a lasting therapeutic effect. This permits precise delivery of bone-healing bioactivity that eliminates the risk of off target effects. The release of AMP2 from the implant is synchronized with implant resorption, thus producing robust bone formation. We used this technology to develop a product called OsteoAdapt, the first biological device of its kind. We have validated OsteoAdapt in models of long-bone repair in rodents, goats, and sheep and demonstrated superiority over the current best treatments available. Objective: Our objective is to advance OsteoAdapt into the clinic. Under this award, we will complete the pharmaceutical-grade manufacturing of OsteoAdapt and preclinical safety studies needed for the Food and Drug Administration (FDA) to approve the start human clinical trials. Human trials are not part of this proposal but will start immediately following completion. Clinical Impact and Relevance to Military Health: The single biggest impact of our product is to increase readiness and accelerate return to duty. The immediate impact it can offer to patients and healthcare providers is a faster bone healing rate, higher resolution of non-unions, shorter length of stay, lower infection rates and better quality of life. The long-term impact is a significant cost saving for the entire healthcare system. Patients with non-healing bone injuries (non-unions) have been found to be more likely to use various types of surgical care, inpatient care, and outpatient physical therapy than those without non-unions. These types of fractures generally exceed the critical size defect limit and do not heal well, requiring multiple revision surgeries to achieve marginal outcomes. Often these injuries force the patient to decide between limb salvage with reduced function, or amputation. Our therapeutic will prevent amputation. In addition, non-union patients are much more likely to be prescribed pain medications, especially strong opioids and have a longer length of opioid therapy than patients without non-union. Improved methods to heal critical fractures or defects by promoting active bone regeneration will produce better outcomes and military health. To maximize the success of our efforts, we have assembled a multi-institutional team that leverages national expertise in orthopedic regeneration from the Mayo Clinic, Cleveland Clinic, and Walter Reed National Military Medical Center. This award would accelerate our path to the clinic.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210875
Entities
People
- Luis Alvarez
Organizations
- United States Army