Abstract
Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation. Despite the clinical signs of full recovery and histological reconstruction, true regeneration of pulp tissues is still far from being achieved. The goal of regenerative endodontics is to promote normal pulp function recovery in inflamed or necrotic teeth that would result in true regeneration of the pulpodentinal complex. Recently, rapid progress has been made related to tissue engineering-mediated pulp regeneration, which combines stem cells, biomaterials, and growth factors. Since the successful isolation and characterisation of dental pulp stem cells (DPSCs) and other applicable dental mesenchymal stem cells, basic research and preclinical exploration of stem cell-mediated functional pulp regeneration via cell transplantation and cell homing have received considerably more attention. Some of this effort has translated into clinical therapeutic applications, bringing a ground-breaking revolution and a new perspective to the endodontic field. In this article, we retrospectively examined the current treatment status and clinical goals of pulpal and periapical diseases and scrutinized biological studies of functional pulp regeneration with a focus on DPSCs, biomaterials, and growth factors. Then, we reviewed preclinical experiments based on various animal models and research strategies. Finally, we summarised the current challenges encountered in preclinical or clinical regenerative applications and suggested promising solutions to address these challenges to guide tissue engineering-mediated clinical translation in the future.
Highlights
Pulpal and periapical diseases, which are two of the most prevalent oral diseases, typically result from irreversible damage to the dental pulp as a result of intense and severe stimuli, such as dental caries, accidental trauma, or iatrogenic causes [1,2]
Muchcases effort has been made to improve clinical closuresuch of pulp revascularisation, andplasma the results indicated that closure was incomplete efficacy, as adding platelet-rich (PRP), platelet-derived growth factor in (PDGF)
CD24a+ cells seem to be an excellent alternative cell source for highly efficient pulp regeneration, especially with respect to cell viability in elderly individuals [69]. It is still unclear whether the regenerative potential of MSCs is conferred by only one subpopulation or several subpopulations; there is no doubt that the application of specific dental pulp stem cells (DPSCs) subpopulations favours the translational management of standardised clinical products as well as the stability between batches, eventually improving the success rate of pulp regeneration [69]
Summary
Pulpal and periapical diseases, which are two of the most prevalent oral diseases, typically result from irreversible damage to the dental pulp as a result of intense and severe stimuli, such as dental caries, accidental trauma, or iatrogenic causes [1,2]. Dental pulp is a highly vascularised and innervated tissue located within rigid dentinal walls, and it performs several functions, such as responding to external signals, providing nutrition and ameliorating neuronal sensitivity by repairing pulp through mineralisation [3] Loss of this tissue results in loss of tooth vitality and requires endodontic treatment. Approved and used in the clinic, pulp revascularisation may be defined as the revascularisation of an immature permanent tooth with an infected necrotic pulp and apical periodontitis/abscess It can promote the root development and reinforcement of dentinal walls by deposition of hard tissue, providing an additional treatment option [9,10]. We summarise the latest advances in functional pulp regeneration mainly from the perspective of applicable cell sources, natural/synthetic biomaterials, growth factors, and different regenerative approaches based on multiple combinations of these elements. We hope that our review can provide a reference with which to direct dental stem cell-mediated clinical transformation in the future
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