Rationale, Scientific Objective, and Aims: The NuCress™ scaffold is a transformative medical device designed to promote fast, functional bone regeneration in patients suffering catastrophic injuries. When approved by the Food and Drug Administration (FDA), this tool will give surgeons a highly versatile option to treat the most challenging and devastating bone injuries. Developed in part with support from the Department of Defense (DoD0, the NuCress™ scaffold offers speed, versatility, and results far superior to the current standards of practice for bone regeneration. The scaffold’s quality and functionality has been proven, and we now seek funding to move it through the final phases of preparation for an application for FDA 510(k) medical device status. In order to solidify and enhance the NuCress™ scaffold’s market and clinical portfolio, we will also (1) verify the scaffold-regenerated bone’s stability and (2) establish recommended practices to guide surgeons in their selection of additives to the scaffold, such as growth factors, antibiotics, and cells, to enhance care of wounded Warriors. Finally, we will establish the next generation of the NuCress™ scaffold family — a dual-use platform that simultaneously and rapidly fights infection and regenerates bone. This added value proposition will be critical for both military and civilian patients, as complex bone breaks frequently involve debilitating infections that complicate healing and prolong recovery. By the end of the proposed project, the NuCress™ scaffold will have not only been submitted for FDA clearance for use in human clinical trials, but sufficient data will have been generated on antibiotic-optimized scaffold to submit it for premarket approval.

Military Benefits: Our scaffold could shift the bone gap treatment paradigm, introducing a dual regenerative and infection-mitigating procedure at the first battlefield surgical element. Designed to be utilized by general surgeons with access to basic surgical equipment, the NuCress™ scaffold will be usable at Role IIb and up. This will close the regenerative window to within the first 6-8 hours of injury and improve wound conditions for future rehabilitation efforts. Return to normal form and function will increase the likelihood that Soldiers and civilians will lead productive lives post-injury. Therefore, the NuCress™ scaffold has the potential to reduce the financial, physical, and psychological burden of bone injuries on the DoD, Soldiers, and civilians. The NuCress™ scaffold is a platform technology, with the first indication being the bare scaffold that we have already shown promotes fast, strong bone regeneration. This proposal will develop the next indication — a drug- and/or growth factor-loaded scaffold to fight infection and regenerate bone simultaneously. All explosion wounds are complicated by dirt, bomb fragments, clothing fibers, and other foreign matter. This contamination causes infection in a fourth of all severe tibial fractures resulting from combat in US and UK Soldiers, delaying and complicating healing and increasing the risk of morbidity. The NuCress™ scaffold’s proposed use as an antibiotic delivery system would directly address the need for early, fast infection-fighting, delivering drugs directly to the wound site and not requiring future surgeries for removal, as many infection-fighting devices do. The ability to simultaneously regenerate bone and deliver clinically relevant drug concentrations represents a transformative improvement to current medical technology.

Ultimate Applicability: Current therapies of bone defects are time-consuming and expensive. Bone grafts from the patient’s own body are the standard of care, but they are not an adequate solution, as the number of potential bone harvesting sites is small and the pain associated with bone harvesting surgery is significant. Alternatively, recent studies have examined bone growth on various synthetic materials, showing that they may be well-suited for accelerated tissue regeneration and enhanced cellular proliferation. However, while synthetic bone grafts resolve the donor issue, the lack of internal blood supply and degradability limit their value. To date, no commercial bone replacement product meets the needs of the surgical community and the patients. Commercially available products have limited sizes and shapes, and surgeons cannot adjust them during surgery. These products are unable to control delivery of antibiotics or growth factors; they cannot prevent infections during and after implantation. In fact, such implants facilitate the harboring of bacteria in the peri-implant biofilm. Therefore, a need remains for a reliable, versatile bone regeneration scaffold for complex bone injuries. The NuCress™ scaffold platform has the potential to fill this major medical and market gap.