Injectable, settable polyurethane biocomposites for bone remodeling in weight-bearing and contaminated fractures.
Harmata, Andrew James
Of the nearly 1.6 million bone graft procedures conducted annually to treat bone fractures in the U.S., ~25% of these fracture patients require rehospitalization due to graft failure. Injectable and settable synthetic bone grafts that possess initial quasi-static mechanical strength and dynamic fatigue resistance exceeding that of host bone and maintain properties comparable to bone while remodeling could improve the clinical management of a number of orthopaedic conditions. Additionally, despite aggressive clinical management tactics, the infection rate of treated severe open fractures with significant bone loss is 23%. Implanted synthetic bone grafts could function as a nidus for bacteria, which could lead to biofilm-induced chronic osteomyelitis. The development of a synthetic bone graft that prevents biofilm formation could prevent osteomyelitis. The goal of this dissertation was to design and characterize synthetic polyurethane (PUR) based graft that possesses initial mechanical properties exceeding those of trabecular bone and remodel in bone defects in vivo. An injectable, settable PUR graft composite comprising poly(ε-caprolactone) surface-modified 45S5 bioactive glass particles exhibited quasi-static compression and torsion, as well dynamic compressive fatigue, mechanical properties equal to or greater than those of native human trabecular bone and commercially available calcium phosphate cements. Additionally, a PUR composite vehicle to deliver biofilm-dispersing D-amino acids (D-AAs) was developed, and the biocompatibility of these D-AAs was further characterized in vitro as well as in a large animal model. At local doses effective for preventing biofilm formation, D-AAs did not inhibit osteoblast and osteoclast differentiation in vitro, or long-term bone healing in vivo. Thus, delivery of D-AAs from a PUR biomaterial is an effective anti-biofilm strategy that does not significantly inhibit bone repair.