GLYCOSAMINOGLYCANS AS BIOMIMETIC REGULATORS OF PULP–DENTIN REPAIR AND REGENERATION: A NARRATIVE REVIEW

Abstract

Background: Glycosaminoglycans (GAGs) are highly specialized extracellular matrix polysaccharides that orchestrate a multitude of biological processes, including cellular adhesion, migration, proliferation, differentiation, and tissue morphogenesis. Owing to their remarkable bioactivity and biomimetic properties, GAGs have garnered considerable interest as therapeutic adjuncts in contemporary endodontics, particularly in vital pulp therapy and regenerative endodontic procedures. Objective: To critically appraise the current evidence regarding the biological functions and clinical applications of glycosaminoglycans in endodontic therapy and pulp–dentin complex regeneration. Methods: A comprehensive literature search was performed across PubMed, Scopus, and Web of Science databases for studies published between 2010 and 2025. Relevant in vitro, in vivo, and clinical investigations evaluating the role of hyaluronic acid, chondroitin sulfate, heparan sulfate, and related glycosaminoglycans in endodontic treatment modalities were systematically reviewed. Results: Accumulating evidence demonstrates that GAG-based biomaterials exert profound regenerative and immunomodulatory effects within the pulp–dentin complex. Hyaluronic acid and chondroitin sulfate have shown significant potential in enhancing pulpal wound healing, attenuating inflammatory responses, and stimulating reparative dentinogenesis. As intracanal medicament vehicles, HA-based formulations improve antimicrobial efficacy while minimizing undesirable sequelae such as tooth discoloration. Furthermore, GAG-enriched scaffolds facilitate stem cell viability, proliferation, and lineage-specific differentiation, thereby creating a conducive microenvironment for tissue regeneration. Heparan sulfate and heparin-functionalized biomaterials have exhibited exceptional capacity to augment angiogenesis, vasculogenesis, and dentinogenesis through growth factor sequestration and modulation of critical signaling cascades, ultimately promoting the formation of a functional pulp–dentin complex. Conclusion: Glycosaminoglycans represent a versatile and biologically sophisticated class of biomolecules with transformative potential in regenerative endodontics. Their ability to emulate the native extracellular matrix, regulate cellular behavior, and enhance tissue repair underscores their value as next-generation biomaterials for pulp preservation and regeneration. Nevertheless, robust longitudinal clinical investigations are warranted to validate their therapeutic efficacy and facilitate their translation into routine clinical practice.