OTA 2005 Posters

Scientific Poster #60 Basic Science

Biphasic Sustained Release of Antibiotics and OP-1 at the Site of Segmental Femoral Defects in Adult Male Rats

Ham A. Benghuzzi, PhD; George Russell, MD; Michelle Tucci, PhD;

Audrey Tsao, MD; Ashraf Ragab, MD (all authors a-OTA/AONA Grant);

University of Mississippi Medical Center, Jackson, Mississippi, USA

Introduction: Management of bone loss associated with open fractures is complex and variable. Antibiotic beads are frequently used in open fractures not only to deliver local antibiotics but also to control dead space in the anticipation of bone graft material. Recent advances in tissue engineering have shown that healing of complicated fractures can be improved by the exposure of the site of injury to bone-promoting agents such bone morphogenic proteins (BMPs). OP-1, also known as BMP-7, has demonstrated accelerated rates of bone union with a femoral defect model in rats. However, the success of OP-1 in femoral shaft osteotomies has not produced similar results. One reason offered to explain this phenomenon is that OP-1 may have to be present for a longer period of time and may have initially diffused away with currently used carriers.

Purpose: Characterizing the dose and duration of OP-1 exposure at the site of a femoral osteotomy will lead to more efficient bone healing.

Methods: Eighty male Sprague Dawley rats were divided equally into four groups. Group 1 served as control. The right femur of the rats in groups II through IV were exposed, plated with a 5-hole plate, and a 5-mm defect in the femoral diaphysis was created. Animals in group II received tobramycin delivery system, while animals in groups III and IV were implanted with delivery system loaded with antibiotic and either OP-1 low or OP-1 high_. Body weights, blood, and radiographs were evaluated weekly. At the end of 1, 2, 3, and 8 months, five animals per group were euthanized and vital and reproductive organs, muscle adjacent to delivery system, and traumatized bone were harvested.

Results: Animals in all groups did not differ in body size for the duration of the experiment. Vital and reproductive weights and morphology were similar for all groups. Blood analysis showed increased activity of alkaline phosphatase in groups III and IV at 1 and 2 months when compared with groups I and II (P<0.05). X-ray analysis and gross evaluation of bone revealed increased bone formation in OP-1 treated groups as early as 1 month, with substantial healing by 3 months. However, the contour of the bone showed evidence of disproportional healing with more bone forming initially above and below the osteotomy site.

Conclusions: A biphasic delivery system can be used to locally deliver a combination of antibiotic and OP-1 to the site of a femoral shaft osteotomy to increase bone formation without evidence of infection. Bone growth is proportional to dose and duration of growth factor.