Nanocrystalline calcium sulfate/hydroxyapatite biphasic compound as a TGF-β1/VEGF reservoir for vital pulp therapy

•Multiple growth factors acted synergistically in biphasic compound.•Controlled release of multiple growth factors from nCS/CS/HAp cement.•Mineralization analysis of nCS/CS/HAp/TGF-β1/VEGF in vivo and in vitro.

ObjectivesVital pulp therapy aims to treat reversible pulpal injuries via protective dentinogenesis and to preserve more tooth structure. Mineral trioxide aggregate (MTA)-based capping materials demonstrate prolonged setting time increases the risk of pulpal infection during multi-visit treatment. Their non-degradable property occupies pulp space and limits dentin-pulp regeneration. This study reports an inorganic degradable biomaterial that presents a short initial setting time and acts as a growth factor reservoir to promote reparative dentinogenesis.MethodsWe synthesize nanocrystalline calcium sulfate hemihydrate (nCS), hydroxyapatite (HAp) and calcium sulfate hemihydrate (CS) as a reservoir to which transforming growth factor-beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF) are added (denoted as nCS/HAp/CS/TGF-β1/VEGF). In vitro biocompatibility and mineralization (the activity and expression of alkaline phosphatase, ALP) were evaluated. Rat animal model was created to test in vivo efficacy.ResultsCultured human dental pulp cells (HDPCs) showed that nCS/HAp/CS/TGF-β1/VEGF cement has excellent biocompatibility and the potential to elevate the activity and expression of ALP. The in vivo efficacy (rat animal model) indicates protective dentin by micro-computed tomography (μ-CT) measurements and histological analyses. The 3D μ-CT non-destructive analysis also determines volume changes during pulpotomy, suggesting that the degraded space of the nCS/HAp/CS/TGF-β1/VEGF cement is repaired by the formation of dentin-pulp tissue.SignificanceThese findings demonstrate that nCS/HAp/CS cement acts as a potent reservoir for the sustained release of growth factors, and that nCS/HAp/CS/TGF-β1/VEGF cement has a high potential to form the reparative dentinogenesis in vivo.

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