A biodegradable antibiotic-impregnated scaffold to prevent osteomyelitis in a contaminated in vivo bone defect model

Abstract

Open fractures are at risk of serious infection and, if infected, require several surgical interventions and courses of systemic antibiotics. We investigated a new injectable formulation that simultaneously hardens in vivo to form a porous scaffold for bone repair and delivers antibiotics at high concentrations to the local site of infection. Duration of antimicrobial activity against Staphylococcus aureus was determined using the serial plate transfer test. Ultimate compressive strength and porosity of the material was measured with and without antibiotics. The material was evaluated in vivo in an ovine medial femoral condyle defect model contaminated with S. aureus. Sheep were sacrificed at either 2 or 13 weeks and the defect and surrounding bone assessed using micro-computed tomography and histology. Antimicrobial activity in vitro persisted for 19-21 days. Sheep with antibiotic-free material and bacteria became infected, while those with antibiotic-containing material and bacteria did not. Similarly, new bone growth was seen in uninoculated animals with plain polymer, and in those with antibiotic polymer with bacteria, but not in sheep with plain polymer and bacteria. The antibiotic-impregnated scaffolds were effective in preventing S. aureus infections whilst supporting bone growth and repair. If translated into clinical practice, this approach might reduce the need for systemic antibiotics.

Antibacterial 3D bone scaffolds for tissue engineering application

“…Studies have shown the application of NO releasing materials in tissue healing processes angiogenesis, inflammation, and proliferation . The hemocompatibility, biocompatibility, and healing attributes of NO releasing polymers have also been positively proven in the recent years . However, more testing on in vivo animal's models is warranted for transitioning into clinical stages for such NO releasing biopolymeric composites.…”

“…Deep infections of bone often occur in the joints and at the ends of long bones . Prevention of bone infections past surgeries require courses of systemic antibiotics and surgeries prior to bone grafting . Unfortunately, even in the light of optimal health management, the chances of infection in open fracture is approximately 30% (of all the cases) …”

The use of nanomaterials to treat bone infections

“…Ideally, the delivery method should allow the antibiotic to release in large concentration at the start and then at a lower but still affective concentration over an extended period of time (days to weeks). 20,22 This allows for efficient prevention of bacterial growth and adaptation to the treatment. Additionally, researchers are trying to find methods that will not only accomplish these goals but to also be able to promote bone growth following the elimination of infection by incorporating agonistic materials in to the delivery systems.…”

“…McLaren et al 22 were only one of a few studies that actually transferred these findings in to an in vivo study. In their study, they surgically injected a PLGA-PEG matrix in to a group of English sheep varying in the amounts of antibiotic and bacteria (S. aureus) received (Table 3).…”

Infected animal models for tissue engineering

“…Sheep long bone osteomyelitis models described in the literature have used a tibial osteotomy [108, 109] or a medial femoral condyle defect [110] inoculated with S. aureus . Control groups in these studies also indicate that it is possible to induce a S. aureus infection in the tibia of sheep, making them an acceptable large animal for osteomyelitis studies.…”