Abstract
Bone infection is a serious complication that may follow surgery or trauma. Antibiotics are the basic treatment for bone infection, but e.g., chronic osteomyelitis in most cases can be treated successfully only when all foreign bodies are removed and surgical intervention is used in combination with systemically administered antibiotic therapy. Besides general measures, and systemic prophylactic antibiotics, a local drug-delivery system is thus needed. Our group in Tampere University of Technology has recently developed the first reliable antibiotic-releasing bone fixation screws in the world. These are based on bioabsorbable high molecular weight self-reinforced (SR) polymers. During the degradation studied screws progressively release the applied antibiotic and still have sufficient mechanical properties over 2-3 months.

The high molecular weight bioabsorbable polymer matrix in antibiotic releasing screws was either amorphous poly(L-lactide-co-D,L-lactide) 70:30 (P(L/DL)LA) or semicrystalline poly(lactide-co-glycolide) 80:20 (PLGA). The antibiotic was ciprofloxacin, which is a synthetic fluoroquinolone and active against a wide range of osteomyelitis-causing bacteria, e.g. S. aureus, S. epidermis and P. aeruginosa. After manufacturing of the screws ciprofloxacin was bacteriologically proved to be bioactive.

All loaded ciprofloxacin was released from the studied screws after 44 weeks (P/L/DL)LA) and 23 weeks (PLGA) in vitro. During that time concentration of released ciprofloxacin per day remained in range of 0.06 – 8.7 µg/ml (P(L/DL)LA) and 0.6 - 11.6 µg/ml (PLGA) after the start-up burst peak. The maximum concentration value of released ciprofloxacin was measured in the 15th week (P(L/DL)LA) and 8th week (PLGA) in vitro week. Ciprofloxacin remained bioactive throughout the in vitro drug release test. In vivo drug release studies are currently in progress. Early results are promising and have shown that osteomyelitis in rabbits can be healed using antibiotic releasing devices.

Initial mechanical properties of the screws are high and their application is easy. Measured initial shear strengths of the studied ciprofloxacin-releasing screws were 152 MPa (P/L/DL)LA) and 172 MPa (PLGA). Studied screws retain their mechanical properties at least 12 weeks (P(L/DL)LA) and 9 weeks (PLGA) in vitro at the level that ensures their fixation properties.

Ciprofloxacin-releasing SR-P(L/DL)LA and SR-PLGA screws have sufficient drug release properties, good mechanical strengths and bacterial inhibitory effect. Clinical studies in osteofixation and infection prophylaxis or therapy will be started in near future.