Evaluation of Strontium-Doped Nanobioactive Glass Cement for Dentin-Pulp Complex Regeneration Therapy

Introducing new generations of injectable bioactive types of cement that fulfill excellent injectability, rapid self-setting, high bioactivity, proper biodegradability, and fast therapeutic ion-releasing capability is highly demanded for tooth and bone regeneration. Here, we announce therapeutic fast ion-releasing nanobiocements (NBCs) based on sol-gel-processed calcium silicate mesoporous nanobioactive glass with or without strontium (NBC, Sr-free and Sr-NBC, Sr-doped). The stimulating role of Sr ions in odontogenesis of stem cells derived from dental pulp (DPSCs) and in in vivo dentin formation has been investigated. The nanobiocement was formulated through the mixing of bioactive glass nanopowder with a phosphate-buffered saline (P/L = 0.5 g/mL) to form a soft cement paste that hardens within 5-10 min in the ambient environment. The self-setting originated from a setting reaction involving the deposition of hydroxyapatite as evidenced from X-ray diffraction. Both nanobiocements showed the rapid release of therapeutic ions with biologically effective doses, including strontium (Sr), calcium (Ca), or silicon (Si). In vitro cell cultures with DPSCs showed excellent biocompatibility and high odontogenic potential, especially from Sr-NBC. In an in vivo study, Sr-NBC showed more new dentin formation compared to that of NBC, revealed by two different animal models (odontogenesis in subcutaneous and natural tooth environment). Also, NBCs showed high loading capacities of simvastatin used as a model drug. Taken together, Sr-NBC could be considered as a multifunctional nanobiocement with high bioactivity, excellent biodegradability, fast therapeutic ion release, and high drug loading capability, which potentiates its application in dentin-pulp complex regeneration therapy.