Evaluation of comparative soft tissue response to bone void fillers with antibiotics in a rabbit intramuscular model

Management of osseous and soft tissue dead space can be a significant challenge in the clinical setting. Calcium sulphate and calcium phosphate-based biomaterials are increasingly being used as alternatives to PMMA for local release of antibiotics, in particular to fill dead space following surgical debridement. This study aims to observe the in-vivo absorption characteristics and tissue response of three commercially available calcium sulphate-based materials combined with gentamicin in an established soft tissue rabbit model. The implant materials (1cc) were placed into four intramuscular sites in 18 New Zealand White rabbits (n = 6). In-life blood samples and radiographs were taken from each animal following implantation. Animals were sacrificed at 0, 1, 7, 21, 42 and 63 days post-operatively (n = 3) and implant sites analysed by micro-computed tomography and histology. Radiographically and histologically, recrystallized calcium sulphate (RCS) absorbed the fastest with complete absorption by day 21. Calcium sulphate/HA composite (CSHA) and Calcium sulphate/calcium carbonate (CSCC) absorbed slower and were detectable at day 63. Residual bead analysis revealed the presence of detectable gentamicin at 24 h and 7 days for CSHA and RCS but none in CSCC. Systemic levels of gentamicin were only detected between 1 h and 24 h. Serological inflammatory cytokine expression for IL-6, TNF-α and IL-1β indicated no unusual inflammatory response to the implanted materials. Calcium sulphate materials loaded with gentamicin are effective in resolving a surgically created dead space without eliciting any adverse host response.