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

Abstract

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.

Eluting antibiotic bone graft substitutes for the treatment of osteomyelitis in long bones. A review: evidence for their use?

“…Using tissue engineering, Xing et al 81 created a biodegradable composite of vancomycin alginate beads and fibrin gel scaffolds to treat chronic osteomyelitis in a rabbit model, promoting positive results. Chang et al 82 confirmed these results in a goat model, reporting a minimum inhibitory concentration (MIC) of vancomycin against S. aureus in a bone defect for at least 28 days.…”

A review of fibrin and fibrin composites for bone tissue engineering

“…182 In their future in vivo study, they showed that inclusion of vancomycin alginate beads/ fibrin in a DBM exhibited no negative impact on the process of osteogenesis and wound healing in the femoral defects of goats. 183 In addition, they successfully treated chronic osteomyelitis of rabbit tibia by a vancomycin alginate bead/ BMSCs/fibrin gel delivery system.…”

The Osteogenetic Efficacy of Goat Bone Marrow-Enriched Self-Assembly Peptide/Demineralized Bone MatrixIn VitroandIn Vivo

“…The final published version may differ from this proof. 14 Currently, no satisfactory results have been reported regarding the clinical application of large bone grafts modified with SAPs. One reason is that the reconstruction of large bone defects remains a challenge (33).…”

“…Goat mesenchymal stem cells (gMSCs) were harvested as previously described (14). Sixty to eighty microliters of cell suspension was instilled slowly onto one side of the post-enriched SAP/DBM or DBM.…”