Experimental Studies On Anti-infective Reconstituted Bone Xenograft And Its Preliminary Clinical Use

With increasing industrial and agricultural mechanization and the use of high- power firearms in modem war, the incidence of severely contaminated or infected bone defects have increased by a big margin, which represents a challenge to orthopaedic surgeons who have since devoted every effort to search for a gratifying treatment option. Traditionally, we proceed with debridement (or clearance of focal lesion) and do not use a bone graft to repair the defect until wound closure and no evidence of infection present themselves by 3-6 months after injury. However, secondary bone grafting rather than the primary bone grafting is the standard treatment option, and the latter has been considered a contraindication in this situation because of the associated higher infection rate. This adds adversely to the difficulty in treatment and increase hospital stay and financial burden to the patients. Based on our previous study on reconstituted bone xenograft (RBX), we developed anti-infective RBX(ARBX) by combining RBX with an antibiotic using gelatin. Serial experimental studies and preliminary clinical use gave some remarkable results as follows: while having high osteoinductive activity, ARBX can slowly deliver the antibiotic at the implant site, thus exerting strong antibacterial effect on the focus; ARBX can repair the bacteria-bearing bone defect by primary grafting, while effectively preventing or treating osteomyelitis. I. Experimental studies 1. Preventive effect of ARBX on osteomyelitis in proximal tibia of the rabbit ?- Aim: To assess possible beneficial effect in prevention of osteomyelitis by ARBX in the rabbit. Methods: A proximal tibia osteomyelitis rabbit model was used in which staphylococcus aureus was injected through a bony window, followed by immediate implantation of three ARBX pellets containing 30mg of slowly-delivered gentamicin in group A, three pellets of RBX mixed with 30mg of gentamicin powder in group B, three pellets of RBX in conjunction with intramuscular gentaniicin (30mg) for 5 days in group C, three pellets of RJ3X without antibiotic in group D, and the focal lesion being left untreated in group E. Specimens were harvested 8 weeks postoperatively for gross observation. radiological, histological and bacteriological evaluation, comparing the five groups with regard to the beneficial effect of the above procedures in preventing osteomyelitis. Results: (1) In group A the bacteria culture and counting yielded 0 values at 8 weeks, while radiologically Nordcn scoring for osteomyelitis gave by far the smallest values among all five groups (P<0.05 or 0.01) with no evidence of osteomyelitis found in gross and histological examinations; (2)bacteria counting, modified Norden scoring, and gross and microscopic examinations for osteomyelitis in groups B, C, E and D were seen in an ascending order of significance (P<0.05 or >0.05). Conclusions: (1) Apart from its osteoconductive and osteoinductive effects, ARBX is capable of slowly delivering antibiotic, thus being highly anti-infective when administered locally, so it could be used for primary grafting to repair a contaminated bone defect for effective prevention of osteomyelitis; (2)conventional systemic, and especially local administration of antibiotics, are reasonably effective in prevention of infection, but their anti- infective effect usually is not strong enough to counteract osteomyelitis when used along with pri...