Polysaccharide-Based Biomaterials in Oral Regenerative Medicine: Mechanisms, Engineering Strategies, and Translational Perspectives

Oral regenerative medicine seeks to repair or regenerate the pulp-dentin complex, periodontal tissues, jawbone, and oral mucosa. Nevertheless, this field confronts considerable challenges, including the intricate oral microenvironment, the body’s limited intrinsic regenerative capacity, and the requirement for coordinated regeneration across multiple tissue types. Natural and engineered polysaccharides have emerged as highly promising regenerative platforms, owing to their excellent biocompatibility, extracellular matrix-mimicking properties, chemical tunability, and capacity for local delivery. This review systematically highlights recent advances in polysaccharide-mediated regeneration of oral and craniofacial tissues. First, polysaccharides are classified into three categories: linear non-sulfated polysaccharides, nitrogen-containing cationic polysaccharides, and sulfated polysaccharides, with an analysis of their structure–function relationships. Second, the key mechanisms through which polysaccharides modulate cellular behavior, reshape the immune microenvironment, regulate biomineralization, and enable the spatiotemporal delivery of bioactive molecules and cell-free therapeutic cargo are clarified. Third, tissue-specific applications of polysaccharide-based materials in pulp-dentin complex regeneration, periodontal tissue regeneration, and craniofacial bone regeneration are systematically reviewed. Furthermore, engineering design strategies—including chemical functionalization, physical assembly, and smart and bioinstructive engineering—alongside advanced manufacturing technologies such as 3D printing, electrospinning, and microsphere-based delivery systems, are discussed. Finally, this review highlights critical challenges in clinical translation, including material standardization, manufacturability, and clinical validation, while proposing future directions centered on mechanism-guided rational design, personalized precision therapy, and AI-assisted development. These insights aim to provide a theoretical framework and practical guidance for advancing next-generation polysaccharide-based biomaterials in oral regenerative medicine.