Cyclic Acetal Hydroxyapatite Nanocomposites for Orbital Bone Regeneration

We have incorporated hydroxyapatite nanoparticles within cyclic acetal hydrogels to create nanocomposites that can be used to repair surgically created orbital floor defects in a rabbit animal model. Nanosized hydroxyapatite particles may improve tissue engineering scaffold properties because they have similar length scale of many cellular and molecular components and therefore can enhance cellular adhesion and migration. We hypothesize that inclusion of nanosized hydroxyapatite particles (20-70 nm) within cyclic acetal hydrogels would support bone defect repair. The objectives of our study include (1) characterization of nanocomposites in vitro, (2) investigation of tissue response and capsule tissue surrounding nanocomposites in vivo, and (3) investigation of the potential of nanocomposites to facilitate bone formation at 7- and 28-day time points in vivo. Experimental nanocomposite groups consisted of 0, 10, and 50 ng/mL nanosized hydroxyapatite. In vitro results indicated uniform dispersion of nanoparticles within nanocomposites and increased compressive moduli of nanocomposites with increase in nanoparticle concentration and bone marrow stromal cell viability within nanocomposites. In vivo results at day 7 indicated a tissue response of mild to increased inflammatory cells and presence of immature fibrous tissue. At day 28, tissue response consisted of mild inflammatory response and mature tissue. Quantitative results at day 7 indicated no difference in total bone percentage area between groups. The results also indicated that the tissue capsule surrounding the 0, 10, and 50 ng group implants had no clear organization. Quantitative results at day 28 indicated that the tissue capsule surrounding the 0, 10, and 50 ng group implants was an organized layer and the bone percentage for the 50 ng group was significantly higher than that of the remaining groups. Initial results indicated that our nanocomposites initiate a positive in vivo response in terms of bone growth. However, the percentage of bone area compared with the total area was low at both time points. Thus, in our study, even after addition of nanoparticles to cyclic acetal hydrogels, their biocompatible properties were maintained. On the other hand, addition of nanoparticles to cyclic acetal hydrogels did not lead to complete restoration of orbital floor defects.