Infection associated with Allograft transplantation and prosthesis use can occur in any patient, and is particularly prevalent and challenging in immunocompromised individuals. When developed, infection can lead to prolonged disability with immense psychosocial and economic cost to the patient and the society. We have recently developed methods to render metal surfaces resistant to bacterial colonization. We now propose to develop an antibiotic-modified Allograft bone that will resist bacterial colonization; by combining it with controlled release of complementary antibiotics, acute infections will be resisted. As a third arm, establishment of chronic infections will be inhibited by inclusion of adhesion peptides that decrease bacterial internalization into bone cells. We propose to: 1. Create an antibiotic-modified bone Allograft that is also loaded with therapeutic amounts of broad-spectrum antibiotics, 2. Characterize the antibacterial properties of the modified bone Allograft, 3. Include tethered RGD's on the modified Allograft to prevent bacterial internalization and promote osteoconduction, and 4. Evaluate Infection-Free Repair of a segmental defect. If successful, this technology will lead to the launch of next generation of Allograft transplant tissue that can resist one of the most dreaded, and on the rise, problem associated with Allograft transplantation, namely infection. PUBLIC HEALTH RELEVANCE: Infection associated with Allograft transplantation can occur in any patient; this problem is particularly prevalent and challenging in immunocompromised individuals where underlying neoplasm are often present. We propose to render Allograft resistant to bacterial colonization for both the long and short term in order to launch the next generation of Allograft transplant tissue that can resist one of the most dreaded, and on the rise, problems associated with Allograft transplantation, namely infection.