(122a) Synthesis and Characterization of Degradable Nanoparticles for Controlled Delivery of Growth Factors for Bone Regeneration

Fractures that fail to heal naturally due to severe trauma, otherwise known as nonunion bone fractures, pose a significant burden on a patient’s lifestyle. Bone tissue engineering systems have recently been explored in an effort to overcome the limitations of current gold standard treatment options for nonunion fractures. Delivery of growth factors in such systems has been of particular interest due to their ability to enhance cell recruitment and promote osteogenic differentiation and angiogenesis. However, current growth factor delivery methods come with their own challenges and have yet to see commercial success. Growth factors are subject to rapid enzymatic degradation and diffusion from the defect site, resulting in the need to deliver supra-physiological doses. Encapsulation of growth factors within particulate carrier systems has been explored as a method to improve protein stability and to provide greater control over release kinetics. Here, we have developed polymeric, hydrolytically degradable nanoparticles to provide controlled release of growth factors for bone tissue engineering applications.

Customizable poly(lactic acid)-b-poly(ethylene glycol) dimethacrylate crosslinking agents were synthesized through a ring opening polymerization reaction, and were subsequently incorporated into poly(methacrylate-co-methacrylic acid) nanoparticles. To achieve a range of degradation profiles, the PLA and PEG chain length in the crosslinker was varied. The crosslinked, co-polymeric nanoparticles were synthesized using UV-initiated free radical emulsion polymerization. Fourier-transform infrared spectroscopy was used to confirm the composition of the resulting nanoparticles and dynamic light scattering and electrophoretic light scattering were used to assess the particle size and zeta potential, respectively. Nuclear magnetic resonance spectroscopy was used to study the influence of polymer composition on degradation kinetics. The particle loading capacity and release profiles were analyzed using chymotrypsin as a model for bone morphogenetic protein-2, a widely studied growth factor for bone regeneration. Ultimately, our work shows that variation of nanoparticle degradation rates can control the release rate of growth factors and provide sustained delivery within a therapeutic timeframe for bone regeneration. In addition, our system shows promise for the potential to sequentially deliver multiple growth factors with physiologically relevant profiles.

The work was supported in part by a grant from the National Institutes of Health (R01 EB022025).