In Situ Gelling Hydrogel with Anti-Bacterial Activity and Bone Healing Property for Treatment of Osteomyelitis

Abstract

Despite the development of progressive surgical techniques and antibiotics, osteomyelitis is a big challenge for orthopedic surgeons. The main aim of this study is to fabricate an in situ gelling hydrogel that permits sustained release of antibiotic (for control of infection) and growth factor (for induction of new bone formation) for effective treatment of osteomyelitis. An in situ gelling alginate (ALG)/hyaluronic acid (HA) hydrogel containing vancomycin (antibiotic) and bone morphogenetic protein-2 (BMP-2; growth factor) was prepared by simple mixing of ALG/HA/Na2HPO4 solution and CaSO4/vancomycin/BMP-2 solution. The release behaviors of vancomycin and BMP-2, anti-bacterial effect (in vitro); and therapeutic efficiency for osteomyelitis and bone regeneration (in vivo, osteomyelitis rat model) of the vancomycin and BMP-2-incorporated ALG/HA hydrogel were investigated. The gelation time of the ALG/HA hydrogel was controlled into approximately 4 min, which is sufficient time for handling and injection into osteomyelitis lesion. Both vancomycin and BMP-2 were continuously released from the hydrogel for 6 weeks. From the in vitro studies, the ALG/HA hydrogel showed an effective anti-bacterial activity without significant cytotoxicity for 6 weeks. From an in vivo animal study using Sprague–Dawley rats with osteomyelitis in femur as a model animal, it was demonstrated that the ALG/HA hydrogel was effective for suppressing bacteria (Staphylococcus aureus) proliferation at the osteomyelitis lesion and enhancing bone regeneration without additional bone grafts. From the results, we suggest that the in situ gelling ALG/HA hydrogel containing vancomycin and BMP-2 can be a feasible therapeutic tool to treat osteomyelitis.