Dual Delivery of BMP-2 and Vancomycin From Polyurethane Scaffold for Infected Bone Wound Healing

摘要

Bone regeneration is required for healing of open fractures, and healing is often complicated by chronic infection. To reduce the healing time of the patient, it is desirable to promote bone fracture healing and control infection through one surgical procedure. Bioresorbable polyurethanes (PUR) have been used extensively in tissue engineering to serve as both a supportive scaffold and drug delivery system due to their biocompatibility and biodegradability (1,2). In the present study, we successfully delivered both bone morphogenetic protein (BMP-2) for the acceleration of new bone formation and antibiotic (vancomycin) for the control of infection from preformed PUR implants which are demonstrated to be bioactive. The release profile of both drugs can be controlled. The PLGA microencapsulation approach resulted in a lower burst and more sustained release profile of BMP-2; and conversion of vancomycin hydrochloride into vancomycin free base before incorporation into polyurethane eliminated the burst release and achieved a more sustained release. The PUR scaffolds have been tested in a rat femoral plug model, and the release of BMP-2 promoted significantly more new bone formation at weeks 2 and 4 relative to the negative control as evidenced by histomorphometry. The scaffold disks containing vancomycin were bioactive as demonstrated by Kirby-Bauer assay.