Antibiotic Incorporated Tissue Engineered Scaffolds for Treatment of Osteomyelitic Defects

Abstract

Osteomyelitis is an infection that results in inflammatory reaction and bone necrosis. The common microorganism responsible for osteomyelitis is Gram-positiveMethicillin resistant Staphylococcus aureus(MRSA). After colonizing the bone, bacteria proliferate, formbiofilm and induce a cascade of inflammatory processes. The infection slowly restricts the blood supply to the bone causing necrosis, which represents the hall mark of chronic osteomyelitis. The clinical management involves surgical removal of the necrotic tissue and antibacterial therapy for 4-6 weeks. However, systemic therapy often results in toxicity. Therefore, current studies are focused on localized antibiotics delivery to the infected site. The most commonly used localized antibiotic delivery system is polymethylmethacrylate (PMMA). The PMMA cement impregnated with antibiotic (vancomycin, gentamycin and tobramycin) can provide temporary structural support, and simultaneously elute high concentrations of antibiotics locally. Nonetheless, PMMA polymerization is exothermic that impair the activity of many antibiotics. It also exhibits poor elution kinetics, which may generate bacterial resistance. Above all, the non-biodegradable nature of PMMA necessitates revision surgery. Alternatively, biodegradable delivery system that facilitates local antibiotic delivery and concurrently enhances the repair and regeneration of bone is preferred.Among different materials, calcium sulfate beads are approved for the treatment of osteomyelitic infections (STIMULAN® - Biocomposites). However, biodegradation of calcium sulfate beads are fast, restricting its use for large critical size defects. In an osteomyelitic site, the scaffold should offer structural support and its biodegradation rate should be proportional to time at which bacterial elimination followed by bone regeneration happens (mostly 1-3 months). Additionally, the graft should stimulate angiogenesis, which is essential to promote the migration of osteoblasts and stem cells, leading to vascularized bone.