Antibiotic‐loaded biodegradable bone cement for prophylaxis and treatment of experimental osteomyelitis in rats

Abstract

A biodegradable, particulate composite bone cement containing gentamicin and vancomycin was used for both treatment and prophylaxis of Staphylococcus aureus osteomyelitis in rats. Osteomyelitis was established by inoculating S. aureus into holes that were drilled in the proximal tibiae and were filled with polymethylmethacrylate (PMMA) cylinders. The cylinders were left in place for 3 weeks. The infections were serially evaluated by clinical and radiographic examination and by quantitative culture for colony forming units (CFUs) at the time the rats were killed. For treatment, cements containing antibiotic were implanted in animals that had established osteomyelitis and were left in place for an additional 3 weeks. Sites treated with biodegradable cement containing antibiotics exhibited significantly fewer CFUs in comparison with controls (p < 0.01). Sites treated prophylactically with the biodegradable cement developed no infections as evaluated by clinical or radiographic criteria or by quantitative culture. At this relatively early time, no significant difference in therapeutic effectiveness was found when either the biodegradable cement or PMMA was used as a carrier for antibiotics.

Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds

“…Bioactive ceramic scaffolds alone used in bone TE can serve as a delivery vehicle of drugs but the drug release patterns are difficult to control (Habraken et al 2007). On the other hand, biodegradable polymeric materials such as poly(lactic-co-glycolic acid) (PLGA) (Garvin & Feschuk 2005) and poly( propylene glycol-fumerate)/ methylmethacrylate (Gerhart et al 1993) can be used to control the local delivery of drugs; however, they show impaired osteoconduction and sometimes they provoke an adverse tissue response owing to inflammation as a consequence of acidic degradation (Böstman & Pihlajamäki 2000). Thus, the smart combination of bioceramics (including calcium phosphates (CaP), hydroxyapatite (HA) and silicate bioactive glasses (BGs)) and biodegradable polymers can not only improve the degradability of the inorganic material and alter its mechanical/physical properties (Rezwan et al 2006), but also drug-release profiles can be controlled to a greater extent than on pure ceramics (Habraken et al 2007).…”

Advances in Biomimetic Apatite Coating on Metal Implants

“…However, the need for a second operation to remove the non-absorbable PMMA beads and the possibility of thermal damage to the antibiotics caused by the exothermic polymerization reaction of the cement is still a problem (Radin et al, 1997). Furthermore, the non-absorbable drug carrier like PMMA, and the biodegradable drug carriers, such as poly(lactide/glycolide) copolymer and poly(propylene glycol-fumerate)/methyl methacrylate composite are non-bioactive ( Gerhart et al, 1993;Garvin & Feschuk, 2005;Henry et al, 1991). Therefore, combining osteoconductive properties of bioactive materials with a local and sustained release of antibiotic can be used to not only enhance early osteointegration of implants, but also prevent post-surgical infections.…”

Experimental Models of Bone and Prosthetic Joint Infections

“…Other related models in rats [27] or rabbits [28] have been radiographs) and continued for 14 days was ineffective, as observed in chronic human osteomyelitis.…”

“…used more recently to test the efficacy of different locally implanted antibiotic composites to prevent [27,28] or cure osteoThe rat model has several advantages over the rabbit model: rats are inexpensive, they are more resistant to the side effects of myelitis [27].…”

“…measured by usual methods, and the success of therapy in experimental models. The difficulty of interpreting bone concentrations is attributed to the heterogenous diffusion of antibi-models in dogs, rabbits, or rats have been used to evaluate the treatment of established osteomyelitis [22,23,27,28] …”