Despite the recent explosion of investigations on dental pulp regeneration using various tissue engineering strategies, the translation of the findings from such studies into therapeutic applications has not been properly achieved. The purpose of this scoping review was to systematically review the efficacy of mesenchymal stem cell transplantation for dental pulp regeneration. A literature search was conducted using five electronic databases from their inception to January 2021 and supplemented by hand searches. A total of 17 studies, including two clinical trials and 15 animal studies using orthotopic pulp regeneration models, were included for the review. The risk of bias for the individual studies was assessed. This scoping review demonstrated that the regeneration of vascularized pulp-like tissue was achieved using the stem cell transplantation strategy in animal models. Autologous cell transplantation in two clinical studies also successfully regenerated vascularized vital tissue. Dental pulp stem cell subpopulations, such as mobilized dental pulp stem cells, injectable scaffolds such as atelocollagen, and a granulocyte-colony forming factor, were the most commonly used for pulp regeneration. The overall risk of bias was unclear for animal studies and was moderate or judged to raise some concerns for clinical studies. More high-quality clinical studies are needed to further determine the safety and efficacy of the stem cell transplantation strategy for dental pulp regeneration.

Invasive cervical resorption (ICR) is a localized, subepithelial, supra-osseous resorptive process of the tooth. Although there are several predisposing factors associated with ICR, its etiology and pathogenesis are poorly understood. The damage to the protective layer on the external root surface appears to allow for the attachment of clastic cells and initiate the resorptive process, which is confined by the inner protective pericanalar resorption-resistant sheet surrounding the root canal space. The use of cone-beam computed tomography (CBCT) is recommended for the diagnosis and assessment of a resorptive lesion. Based on the thorough evaluation of the size and location of the ICR lesion using CBCT, surgical or nonsurgical treatment can be chosen to address the source of the resorption. This review discusses the current status of knowledge regarding the biology of ICR lesions as well as their external or internal treatment using hydraulic calcium silicate-based materials. Future clinical outcome studies are necessary to evaluate the impact of hydraulic calcium silicate-based materials on the healing of ICR lesions.

Control of blood clotting in root canal systems is one of the most critical and difficult concerns for regenerative endodontics therapy (RET). The purpose of this study was to investigate the effects of using gelatin- and fibrin-based hemostatic hydrogels as a scaffold on pulp regeneration in a minipig model. Cell viability of human dental pulp stem cells cultured three-dimensionally in gelatin-based and fibrin-based scaffolds was evaluated by MTT and live/dead assay. RET was performed on 24 immature premolars with an autologous blood clot (PC), gelatin-based and fibrin-based hemostatic matrices (GM and FM), or without the insertion of a scaffold (NC). The follow-up period was 12 weeks. Radiographic and histologic assessments for pulp regeneration were performed. Gelatin-based scaffolds exhibited significantly higher cell viability than fibrin-based scaffolds after 15 days (P < 0.05). The PC and GM groups showed favorable root development without inflammation and newly mineralized tissue deposited in the root canal system, while FM group presented inflammatory changes with the continuation of root development. The NC group exhibited internal root resorption with periapical lesions. The application of GM in RET led to favorable clinical outcomes of root development without inflammatory changes compared to conventional RET. Our results suggest that GM may serve as a viable regenerative scaffold for pulp regeneration.

Cell homing, a process that leverages the body’s natural ability to recruit cells and repair damaged tissues, presents a promising alternative to cell transplantation methods. Central to this approach is the recruitment of endogenous stem/progenitor cells—such as those from the apical papilla, bone marrow, and periapical tissues—facilitated by chemotactic biological cues. Moreover, biomaterial scaffolds embedded with signaling molecules create supportive environments, promoting cell migration, adhesion, and differentiation for the regeneration of the pulp–dentin complex. By analyzing in vivo animal studies using cell homing strategies, this review explores how biomolecules and scaffold materials enhance the recruitment of endogenous stem cells to the site of damaged dental pulp tissue, thereby promoting repair and regeneration. It also examines the key principles, recent advancements, and current limitations linked to cell homing-based regenerative endodontic therapy, highlighting the interplay of biomaterials, signaling molecules, and their broader clinical implications.

The dehydrated human amnion–chorion membranes (dHACMs) derived from the human placenta have emerged as a promising biomaterial for dental pulp regeneration owing to their unique biological and structural properties. The purpose of this review is to explore the potentials of dHACMs in dental pulp tissue engineering, focusing on their ability to promote cellular proliferation, differentiation, angiogenesis, and neurogenesis. dHACMs are rich in extracellular matrix proteins and growth factors such as TGF-β1, FGF2, and VEGF. They also exhibit significant anti-inflammatory and antimicrobial properties, creating an optimal environment for dental pulp regeneration. The applications of dHACMs in regenerative endodontic procedures are discussed, highlighting their ability to support the formation of dentin and well-vascularized pulp-like tissue. This review demonstrates that dHACMs hold significant potential for enhancing the success of pulp regeneration and offer a biologically based approach to preserve tooth vitality and improve tooth survival. Future research is expected to focus on conducting long-term clinical studies to establish their efficacy and safety.