Effect of resveratrol release kinetic from electrospun nanofibers on osteoblast and osteoclast differentiation

Resveratrol (RSV) has been shown to exhibit many biological properties that can influence bone osteogenesis. However, RSV oral clinical treatment is limited due to its poor pharmacokinetics, low water solubility, and rapid metabolism. Therefore, it is necessary to develop a valid delivery system to release RSV directly into the target site. Electrospun drug-eluting fibers have gained great attention in the regenerative dentistry due to the ease of fabrication, the high surface to volume ratio and the drug-loading efficiency. The post-extraction preservation of the alveolar socket requires to operate on the bone remodeling processes both by stimulation of bone formation by osteoblasts and inhibition of osteoclast-mediated bone resorption. In this work, uniform defect-free fibers of poly(e-caprolactone) PCL and poly(lactic) acid (PLA) loading resveratrol were synthetized and characterized. In vitro assay demonstrated that the two membranes were able to release RSV in a tunable and sustained manner with different kinetic: PCL-RSV membrane showed an initial burst followed by a slow release, while PLA-RSV presented a much slower and continuous release over the time. Although both RSV-loaded materials showed similar in vitro osteoinductive capacity on human dental pulp stem cells, the differences on RSV release kinetic affected RANKL-induced osteoclastogenesis. Indeed, only the lower resveratrol-releasing membrane (PLA-RSV) was able both to induce osteoblast and to inhibit osteoclast differentiation, suggesting that this bioactive membrane could be used to preserve post-extraction alveolar ridge volume acting simultaneously on two fronts: first counteract bone resorption, second allows new bone formation.