Experimental Research Of Prepared Hollow Hydroxyapatite Microspheres Loaded With Simvastatin As Pulp Capping Agent

Dental pulp is a kind of connective tissue which possess repair and regeneration capacity. When it is subjected to inflammatory stimulation or mechanical damage, the reparative regeneration ability has great significance for preservation of vital pulp. Direct pulp capping or partial pulpotomy is a method of treatment in which the exposed dental pulp is covered with a material protecting the pulp from additional injury and stimulating healing and repair. Ultimately, the goal of treating the exposed pulp with an appropriate pulp-capping material is to promote the odontoblastic differentiation of the pulp cells. The result is related to time, size and infection extent of exposed pulp as well as property of pulp capping agent. In this respect, appropriate pulp capping agent is the key to ensure success of the therapeutic method.Simvastatin, a hydroxymethylglutaryl-coenzyme Areductase inhibitor, is known to be used clinically to reduce blood cholesterol levels. Recently, it has been reported that simvastatin in low concentration（10-7¹0-9mol/L） can accelerate proliferation, secreting vascular endothelial growth factor（VEGF） as well as mineralizating of dental pulp cells.This found suggested simvastatin as a potential supplemental pulp-capping agent. Simvastatin in high concentration can suppess proliferation, leading to apoptosis of dental pulp cells. However, local high concentration can be formed if we simply put simvastatin on the exposed dental pulp. Therefore, it needs to find a suitable carrier to constitute local drug delivery system, the sustained low concentration of simvastatin can achieve the best effect of protecting dental pulp.Hydroxyapatite(Ca₁₀（PO₄）₆（OH）₂, HAp) is the main inorganic constituent of bones and teeth, which possess excellent biocompatibility, osteoconductivity, bioactivity and nontoxicity. It has been widely used in biomedical materials, environmental engineering, chemical and technological fields.Morever, hydroxyapatite can absorb a variety of chemicals. Hollow hydroxyapatite microsphere could provide an excellent device for sustained local delivery of drugs because of its hollow interior and nanoporous shell.In this paper, inspired by the idea of biological mineralization, we prepared inorganic minerals with specific morphology utilizing organic molecules. This process is called biomimetic synthesis. Since the organic macromolecule are usually degraded intomicromolecules, the main macromolecule closely with human life protein can be degreded into amino acids gradually migrating over time. Protein fragments associated with enamel mineralization such as amelogenin and dentin sialophosphoproteins contain highly repeated sequences of aspartic acid and phosphorylated serine. These amino acids are known to have strong interactions with Ca2+. In this study, hollow hydroxyapatite microspheres were synthesized utilizing amino acids（ aspartic acid） and sodium dodecyl sulfonate（SDS） “core-shell” complex serving as templates. This method implements simplification for preparation and controllability of hollow microspheres surface morphology.Based on the principles of biomimetic synthesis, hollow hydroxyapatite microspheres were fabricated with one step strategy utilizing amino acids（ aspartic acid） and sodium dodecyl sulfonate（SDS） “core-shell” complex serving as templates. The as-prepared hollow hydroxyapatite microspheres were loaded with simvastatin following drug loading and encapsulation efficiency and in vitro sustained-release time calculated.The model of direct dental pulp capping of maxillary first molars of Wistar rats were established, the drug loaded microspheres containing different concentration of simvastatin,hollow hydroxyapatite microspheres without simvastatin and calcium hydroxide were applied on the exposed dental pulp, the dental pulp without treatment worked as control group. The results showed that the prepared hollow hydroxyapatite microspheres were 3⁵μm with thickness for the shell 0.5¹Î¼m and constructed by short needle nanoparticles. The microspheres exhibit excellent drug-loading capacity and sustained release property, the release behavior followed nearly linear release profile. The drug loaded microspheres containing certain concentration of simvastatin show its excellent biocompatibility and potency in promoting the formation of reparative dentin after pulp capping.