METHODS: Tobramycin (30 mg/mL) was incorporated into CPB by dipping method and the efficacy of TOB-loaded CPB was studied in a rabbit osteomyelitis model. For juxtaposition, CPB with and without TOB were prepared. Twenty-five New Zealand white rabbits were grouped (n = 5) as sham (group 1), TOB-loaded CPB without S. aureus (group 2), S. aureus only (group 3), S. aureus + CPB (group 4), and S. aureus + TOB-loaded CPB (group 5). Groups infected with S. aureus followed by CPB implantation were immediately subjected to surgery at the mid-shaft of the tibia. After 28 days post-surgery, all rabbits were euthanized and the presence or absence of chronic osteomyelitis and the extent of architectural destruction of the bone were assessed by radiology, bacteriology and histological studies.
RESULTS: Tobramycin-loaded CPB group potentially inhibited the growth of S. aureus causing 3.2 to 3.4 log10 reductions in CFU/g of bone tissue compared to the controls. Untreated groups infected with S. aureus showed signs of chronic osteomyelitis with abundant bacterial growth and alterations in bone architecture. The sham group and TOB-loaded CPB group showed no evidence of bacterial growth.
CONCLUSIONS: TOB-incorporated into CPB for local bone administration was proven to be more successful in increasing the efficacy of TOB in this rabbit osteomyelitis model and hence could represent a good alternative to other formulations used in the treatment of osteomyelitis.
Materials and Methods: Cell viability and cytotoxicity of gelatin (Gel; 50 µg/µl), chitosan (Chi; 20 µg/µl), hydroxyapatite (HA; 50 µg/µl), nanohydroxyapatite (nHA; 10 µg/µl), three-calcium phosphate (TCP; 50 µg/µl) and strontium carbonate (Sr; 10 µg/µl) were evaluated on hADSCs via MTT assay. In vivo femoral drill-bone hole model was produced in rats that were either left untreated or treated with autograft, Gel, Chi, HA, nHA, TCP and Sr, respectively. The animals were euthanized after 30 days. Their bone holes were evaluated by gross-pathology, histopathology, SEM and radiography. Also, their dry matter, bone ash and mineral density were measured.
Results: Both the Gel and Chi showed cytotoxicity, while nHA had no role on cytotoxicity and cell-viability. All the HA, TCP and Sr significantly improved cell viability when compared to controls (P<0.05). Both the Gel and Chi had no role on osteoconduction and osteoinduction. Compared to HA, nHA showed superior role in increasing new bone formation, mineral density and ash (P<0.05). In contrast to HA and nHA, both the TCP and Sr showed superior morphological, radiographical and biochemical properties on bone healing (P<0.05). TCP and Sr showed the most effective osteoconduction and osteoinduction, respectively. In the Sr group, the most mature type of osteons formed.
Conclusion: Various biomaterials have different in vivo efficacy during bone regeneration. TCP was found to be the best material for osteoconduction and Sr for osteoinduction.