Regenerative endodontic procedures for immature permanent teeth with apical periodontitis confer biological advantages such as tooth homeostasis, enhanced immune defense system, and a functional pulp-dentin complex, in addition to clinical advantages such as the facilitation of root development. Currently, this procedure is recognized as a paradigm shift from restoration using materials to regenerate pulp-dentin tissues. Many studies have been conducted with regard to stem/progenitor cells, scaffolds, and biomolecules, associated with pulp tissue engineering. However, preclinical and clinical studies have evidently revealed several drawbacks in the current clinical approach to revascularization that may lead to unfavorable outcomes. Therefore, our review examines the challenges encountered under clinical conditions and summarizes current research findings in an attempt to provide direction for transition from basic research to clinical practice.

Epoxy resin-based sealers are currently widely used, and several studies have considered AH Plus to be the gold-standard sealer. However, it still has limitations, including possible mutagenicity, cytotoxicity, inflammatory response, and hydrophobicity. Drawing upon the advantages of mineral trioxide aggregate, calcium silicate-based sealers were introduced with high levels of biocompatibility and hydrophilicity. Because of the hydrophilic environment in root canals, water resorption and solubility of root canal sealers are important factors contributing to their stability. Sealers displaying lower microleakage and stronger push-out bond strength are also needed to endure the dynamic tooth environment. Although the physical properties of calcium silicate-based sealers meet International Organization for Standardization recommendations, and they have consistently reported to be biocompatible, they have not overcome conventional resin-based sealers in actual practice. Therefore, further studies aiming to improve the physical properties of calcium silicate-based sealers are needed.