Degradation and biocompatibility of a fumarate-based/alumoxane nanocomposite for bone tissue engineering
Mistry, Amit S.
Mikos, Antonios G.
Doctor of Philosophy
In this work, a novel biomaterial composed of ceramic nanoparticles and a biodegradable polymer was evaluated for its potential as a tissue engineering scaffold for the treatment of severe bone injuries. Tissue engineering employs a biomaterial scaffold to deliver bioactive molecules and cells into a defect to promote natural healing as opposed to current treatments which are often problematic and ineffective. This biomaterial scaffold must: (1) provide mechanical support; (2) act as a substrate for bone growth (osteoconductivity); (3) degrade in a controlled manner; and (4) exhibit biocompatibility. A promising biodegradable, fumarate-based polymer for these applications was significantly improved in terms of mechanical properties by the incorporation of surface-modified alumoxane nanoparticles. This novel nanocomposite was then evaluated for its degradation and biocompatibility with consideration of its mechanical properties and osteoconductivity. First, solid formulations of fumarate-based polymers and nanocomposites underwent accelerated degradation and were characterized at various stages of degradation for mass loss, mechanical properties, in vitro cytotoxicity, and in vivo soft tissue response. Then, porous scaffolds of the same materials were characterized for in vitro and in vivo degradation and in vivo hard tissue response. Solid nanocomposite scaffolds eroded at the same rate or faster than the polymer alone and also sustained compressive mechanical properties longer than the polymer alone during accelerated degradation. Furthermore, the nanocomposite demonstrated the same in vitro cytocompatibility and in vivo soft tissue compatibility as the polymer alone. Predegraded nanocomposites exhibited more pronounced inflammatory responses than the polymer alone, though this was attributed to the advanced degradation of the nanocomposite rather than its composition. Porous scaffolds fabricated from fumarate-based polymers and alumoxane nanocomposites eroded very slowly but maintained their mechanical properties during 12 weeks of in vitro degradation. Finally, the presence of alumoxane nanoparticles in the fumarate-based polymer had no influence on in vivo degradation or the hard tissue response towards these materials. Thus, this work demonstrated unique characterization methods for degradable biomaterials on shortened timescales and also showed that the incorporation of alumoxane nanoparticles into a fumarate-based polymer enhanced its mechanical properties and degradation without adversely affecting its biocompatibility.
Biomedical engineering; Chemical engineering