DESCRIPTION (provided by applicant): The incidence of traumatic facial injuries relative to injuries at the other anatomic locations has risen sharply during combat operations in Iraq and Afghanistan compared to previous military conflicts. Evan in the civilian population, traumatic craniofacial bone injury is often accompanied by injury or loss of surrounding soft tissues. There are reports of local complications and wound infection rates as high as 100% in civilians suffering gunshot wounds to the face. In the cases of open fractures that involve bone defects, the surgeon must find a way to quickly repair the wound while reducing the risk of chronic infection or osteomyelitis. In the Phase I program, we propose to develop a superior local antibiotic delivery system (in the form of beads) that also possesses resorbable and osteoinductive properties. The beads would be made of biodegradable magnesium. The beads will be coated with hydroxyapatite (HA) incorporated with gentamycin. The HA coating will be applied using Spire's commercial TPA process which produces a thin (5-10¿m) layer at a low temperature, thereby retaining the original chemical composition and phase of the HA source material. HA is well-known to initiate and expedite bone growth. We propose a system in which the HA will initiate bone growth; as the HA starts to dissolute slowly, the Mg will also degrade allowing the antibiotic to be distributed locally, preventing infection. Most importantly, there wil be no need for a subsequent operation to remove any implant or bead from the site.

This is a resubmission of Spire Biomedical's Phase I proposal, "Antimicrobial Biodegradable Bone Graft for Craniofacial/Maxilliofacial Application," which received a score of 42 in July 2012. The resubmission has been significantly modified to reflect the reviewers' highly relevant comments. Military and civilian surgeons have a significant need for a biodegradable implant that can deliver antibiotics to the site of a bone fracture and replace craniofacial bone defects. Hospitalizations due to injuries and injury-related bone replacement and reconstruction were the leading cause of hospitalization for the Army, Navy and Marine Corps, and the second leading cause of hospitalization for the Air Force. A fracture can account for over 100 lost duty days. Gentamycin-loaded magnesium beads with HA coating would provide an ideal system for bone healing and prevention of infection. Furthermore, the beads would not have to be removed in a second operation, thus reducing the chance of post-operative sepsis. This treatment system could potentially reduce the number of days a soldier is unavailable to report for duty. The field of osteobiologics has gained increased visibility over th last decades as a number of products have been developed that promote bone healing and bone growth. The market for products containing osteobiologics, such as bone morphogenetic proteins and hydroxyapatite, was estimated to be $500 million worldwide and $300 million in U.S., which is 4% of the total market in both cases. In many orthopedic surgical procedures, it may be necessary to implant scaffold or bone graft substitute to enhance the bone healing. Recently, spinal fusion procedures remain the top application area for coated biodegradable scaffold and bone substitute (see figure below).38 The oral and maxillofacial market accounts for 11% of bone graft market. There are multiple end-users that we can offer our coated biodegradable graft in this market. After the Phase I is completed, we anticipate conducting a two year Phase II study, which would yield in vivo results of prototype implants through continuing collaboration with our academic partners and also would be guided by active participation of a craniofacial/maxilliofacial surgeon. Assuming favorable results, a 510K would be submitted to the FDA within 6-12 months, since comparisons to predicate devices could be provided. The developed technology would be marketed primarily to comprise in the osteobiologics field. Using coating deposition procedures, HA, which is protected by IP, and data derived in this program, Spire will endeavor to secure a company with significant market presence as a commercial partner. Either the technology could be transferred or the Mg beads could be manufactured by a vendor and the HA coating process could be done at Spire. Spire Biomedical has extensive experience in developing and marketing implantable medical devices. Spire is ISO 13485:2003 certified and has an experienced regulatory team. Additionally, for the past 25 years, Spire has marketed its patented coating and surface modification services. Due to the great potential for the proposed bone repair material to succeed and Spire's experience and accomplishments in the areas of surface modification and production of finished medical products, it appears that the proposed product has a high probability of commercial success.