(190d) Biodegradable, Injectable Poly(Ester Urethane)Urea Delivery Systems for Bone Tissue Engineering
AIChE Annual Meeting
Tuesday, November 14, 2006 - 9:30am to 9:50am
In the US an estimated 643,000 bone graft procedures were performed in 2002 at a cost of $750 million, thereby making bone the second most frequently transplanted tissue after blood. Autogenous bone transplanted from a donor site in the patient to the recipient site has the best outcome for repair of tissue defects due to its osteogenic, osteoinductive, and osteoconductive properties. However, availability of donor tissue is limited and explantation introduces a significant risk of donor-site morbidity. Due to the increasing frequency (e.g., 10% per year) of bone graft procedures, the demand for new clinically effective materials that have the availability of synthetics and the efficacy of autograft will continue to grow.
Poly(ester urethane)ureas synthesized from aliphatic polyisocyanates and polyester polyols have been reported to support the attachment, proliferation, and differentiation of osteoprogenitor cells in vitro. We postulate that polyurethanes have unique properties making them potentially useful as synthetic injectable bone void fillers: (1) the material can be injected as a two-component reactive liquid mixture which gels in situ, (2) porosity and pore size can be controlled by tuning the surface chemistry, and (3) biologically active molecules that enhance the healing of open bone fractures can be delivered.
We have synthesized two-component poly(ester urethane)urea foams from lysine triisocyanate (LTI), aliphatic polyisocyanate trimers prepared from hexamethylene diisocyanate (HD), and a hardener component comprising a polyester polyol, water, catalyst, stabilizer, and pore opener. We present initial physical, mechanical, physicochemical, and biological analyses of the materials. Pore size was determined by SEM. The storage and loss moduli were measured by dynamic mechanical analysis. The in vitro degradation rate in PBS at 37oC, as well as the composition of the degradation products, were also measured. In vivo biocompatibility and osteoconductivity was evaluated by implanting the materials in the tibia of a rabbit followed by harvesting of experimental sites after 8 weeks. Our results demonstrate that the porosity and pore size distribution can be controlled by varying the amount of water and stabilizer in the hardener. The foams are degradable and lose approximately 5 ? 30% of their initial mass after 12 weeks in PBS. These preliminary results imply that the poly(ester urethane)urea foams are promising candidates for future development as injectable, biodegradable delivery systems for bone tissue engineering.