The use of tissue sealants to deliver antibiotics to an orthopaedic surgical site with a titanium implant.

BACKGROUND: Orthopaedic surgery is associated with unacceptable infection rates that respond poorly to systemic antibiotics. The objective of this study was to use an animal model for orthopaedic implant infection to examine the ability of a new-generation fibrin tissue sealant to effectively deliver antibiotics to the surgical site. METHODS: The antibiotics cefazolin, fusidic acid or 5-fluorouracil were blended into Vitagel tissue sealant. The release rate of the drugs was measured using HPLC methods and bioactivity was measured by the zone of inhibition method with pathogenic Staphylococcus aureus. The antibiotic activity of the drug-loaded sealant was then tested in rats using infected orthopaedic surgical sites (titanium clip on spine). Efficacy was evaluated by residual bacterial counts on clips, clinical observations of infection, and histological findings. RESULTS: The drugs were released in a controlled manner over 2-4 days. All three antibiotics demonstrated strong antibacterial activity when released from the sealants. None of the treated animals demonstrated systemic illness. Post mortem dissection revealed a well-encapsulated abscess surrounding the titanium clip with erosion of the bony process. Using an inoculum of 1-5 × 10(3) CFU, treatment with antibiotic-loaded fibrin sealant demonstrated reduced infective swelling and reduced bacterial counts on surgical clip swabs compared to control rats or rats treated with antibiotic only. This model allowed for almost 100 % infectivity with a 0 % mortality rate due to infection, mimicking the clinical features of human implant infection. CONCLUSION: The results support the use of antibiotic-loaded commercially available fibrin sealants to prevent infection after implant surgery.

Fucoidan film safely inhibits surgical adhesions in a rat model.

BACKGROUND: The purpose of this study was to evaluate the in vivo efficacy of 13 compounds and to further characterize the load limiting and potential toxicity of the most efficacious compound. The cascade of biochemical and molecular events that results in the formation of postsurgical adhesions provides numerous theoretical opportunities for prophylactic intervention. METHODS: Candidate agents were loaded into sodium hyaluronate (HA) films and administered to male Sprague-Dawley rats using a cecal-sidewall model of surgical adhesions. An adhesion score was obtained for each rat based on the strength and extent of the adhesions. The most efficacious agent, fucoidan, was further evaluated in a load-limiting study with a concentration range of 0.0033 to 33% w/w per film. The potential toxicity of fucoidan was evaluated in a separate study by comparison of hematology findings, blood chemistry, urinalysis, and incision thickness from rats administered control films or 33% w/w fucoidan films 1 to 4 d prior to sacrifice. RESULTS: Fucoidan loaded films reduced adhesion scores by approximately 90% compared with control films (P<0.05). A total of 50% to 100% of animals were adhesion free at fucoidan film loadings of 0.33% to 33% w/w compared with all control film animals having adhesions. No adverse effects were observed from 33% w/w fucoidan films equivalent to approximately 30 mg fucoidan/kg body weight. CONCLUSIONS: Local administration of fucoidan film during rat cecal-sidewall surgery safely reduced adhesion scores by approximately 90% and resulted in 50% to 100% of animals being adhesion free.