Regenerative matrices for oriented bone growth in craniofacial and dental repair

Abstract

Non-healing fractures can result from trauma, disease, or age-related bone loss. While many treatments focus on restoring bone volume, few try to recapitulate bone organization. However, the native architecture of bone is optimized to provide its mechanical properties. Hyaluronic acid (HA) hydrogel scaffold systems with tunable degradation properties were developed for the controlled delivery of osteoinductive and angiogenic growth factors, thus affecting the quantity and quality of regenerated tissue. First, scaffolds delivering bone morphogenetic protein-2 (BMP-2) were evaluated in a rat calvarial bone critical size defect model. BMP-2 delivery from the HA hydrogels had a clear osteoinductive effect in vivo. The temporal progression of this effect could be modulated by altering the degradation rate of the scaffold. Interestingly, all three degradation rates tested resulted in similar amounts of bone formation at the latest (six week) time point examined. However, the fastest and slowest degrading scaffolds seemed to result in more organized bone than the intermediate degrading scaffold, which was designed to degrade in 6-8 weeks to match the healing time. Second, this defect model was modified to allow non-invasive imaging using optical coherence tomography (OCT) to temporally characterize tissue regeneration in living animals. The temporal progression of healing could be observed by imaging the migration of the bone/defect interface over time, particularly for animals receiving HA hydrogels loaded with BMP-2. Additionally, structures consistent with the neovascularization of the implant could clearly be observed at later time points for animals receiving HA hydrogels loaded with vascular endothelial growth factor (VEGF). These structures correlated with the location of blood vessels seen in histological sections and showed interconnectivity and branching in three dimensions.