(134a) In Vivo Hard Tissue Response and Degradation of Porous Fumarate-Based Polymer/alumoxane Nanocomposites for Bone Tissue Engineering

Introduction. Scaffolds for bone tissue engineering are designed with consideration of mechanical properties, osteoconductivity, degradability, and biocompatibility. In this work, porous scaffolds composed of fumarate-based polymers and alumoxane nanoparticles were fabricated and then evaluated for in vivo hard tissue response and in vivo degradation.

Methods. Scaffolds were prepared by photo-crosslinking and salt-leaching from three materials: poly(propylene fumarate)/propylene fumarate-diacrylate (PPF/PF-DA) polymer alone; PPF/PF-DA with a 1 wt. % loading of boehmite microparticles (macrocomposite group); and PPF/PF-DA with a 1 wt. % loading of surface-modified alumoxane nanoparticles (nanocomposite group). The boehmite particles in the macrocomposite are known to aggregate into large clusters that weaken a material. On the other hand, the surface-modified alumoxane nanoparticles in the nanocomposite significantly improved the mechanical properties of the PPF/PF-DA polymer in a previous study [1]. Additionally, a low molecular weight (MW) PPF polymer group was tested as a control for degradability. Scaffolds were implanted in the lateral femoral condyles of adult goats for 12 weeks and evaluated by micro-computed tomography (micro-CT) and histological analysis.

Results and Discussion. In general, most scaffolds were filled with soft-tissue, some inflammatory elements, and some immature bone tissue after 12 weeks in vivo. Both micro-CT and histology revealed that the presence of alumoxane nanoparticles in PPF/PF-DA had no effect on bone formation in the defects. Some degree of bone growth into the porous network of scaffolds was observed in 60-70% of sections from the PPF/PF-DA polymer, macrocomposite, and nanocomposite groups. Bone growth was also observed in 23% of sections from the degradation control group. The response at the interface between the implant and the surrounding tissue was typically characterized by a thin fibrous capsule. Direct contact between the exterior of the implants and the surrounding bone tissue was observed in 30-40% of sections from PPF/PF-DA-based materials and in 58% of sections from the control group. Once again, the presence of alumoxane nanoparticles had no effect on the bone tissue response at the implant-tissue interface. In vivo degradation was scored based on observations of fragmentation and polymer dissolution at the edges of scaffolds. Though very limited degradation was observed in PPF/PF-DA-based scaffolds, the presence of alumoxane nanoparticles in the polymer was found to have no detrimental influence on in vivo degradation. In summary, the incorporation of surface-modified alumoxane nanoparticles into fumarate-based polymers provides mechanical reinforcement without any detrimental effect on hard tissue response or in vivo degradation.

Reference. 1. Horch, RA, Shahid, N, Mistry, AS, Timmer, MD, Mikos, AG and Barron, AR. Nanoreinforcement of poly(propylene fumarate)-based networks with surface modified alumoxane nanoparticles for bone tissue engineering. Biomacromolecules 5, 1990-1998 (2004).