An Anti-Infection Tissue-Engineered Construct Delivering Vancomycin: its Evaluation in a Goat Model of Femur Defect

A tissue-engineered construct (TEC) has previously been used for treating bone defects due to its strong osteogenic capability. However, transplantation of a TEC involves an open surgery that can cause infection. To overcome the potential risk of infection after TEC transplantation, we designed a system for the controlled release of antibiotics using fibrin gel-coated vancomycin alginate beads (FG-Vanco-AB) that can supply sustained antibiotics at the graft site. A TEC with FG-Vanco-AB was transplanted into critically sized bone defects of the right femur in a goat. As a control, the TEC without FG-Vanco-AB was transplanted into the left femur defect of the same goat. The breakpoint sensitivity of vancomycin for S. aureus (5 mg/L) was used as a known standard. Study results showed that the duration of time with vancomycin concentrations greater than 5 mg/L in the right graft site, blood, and left graft site were 28 days, 7 days, and 2 days, respectively. The bioactivity regarding vancomycin release was analysed by antibiotic disc diffusion. The vancomycin concentration was decreased from the centre of the graft to both ends of the femur. Radionuclide bone imaging showed no significant difference between the right and left TECs at either 28 or 56 days post-operation. Computed tomography and histological observation showed both sides' bone defects were healed by TEC at 112 days post-operation, and there was no significant difference in computed tomography value. These results suggest that FG-Vanco-AB in transplanted bone provided the ability to kill bacteria in local bone tissue while not interfering with the process of bone reconstruction and wound healing.