ABSTRACT Periodontal disease is a chronic, infection-driven inflammatory condition that progressively destroys the tooth-supporting tissues and remains a principal cause of tooth loss worldwide. Its multifactorial pathogenesis involves dysbiotic biofilms, immune dysregulation, and genetic as well as environmental factors, linking it to broader systemic health risks. Conventional nonsurgical periodontal therapy (NSPT), such as scaling and root planning, with or without antibiotics, remains standard practice but is limited by incomplete bacterial eradication, recurrence, and emerging antimicrobial resistance. A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published between 2010 and 2024. Approximately 120 preclinical and clinical studies were critically reviewed to evaluate the efficacy, mechanisms of action, and translational potential of alternative periodontal therapies. Emerging evidence highlights the promise of several innovative modalities, including antimicrobial photodynamic therapy, probiotics, prebiotics, hostmodulatory agents, mesenchymal stem cell-conditioned medium (MSC-CM), nanotechnology-based systems, and stimuli-responsive biomaterials. Intelligent biomaterials and nanomedicine demonstrate targeted antimicrobial and regenerative potential, MSC-CM provides a cell-free regenerative strategy with minimal immunogenicity, and microbiome-focused approaches promote restoration of microbial-host homeostasis rather than mere pathogen elimination. Future research should emphasize safe, personalized, and multimodal periodontal therapies that integrate omics-based diagnostics with advanced biomaterials. Such approaches hold potential to overcome current limitations of NSPT and achieve predictable, long-term periodontal regeneration.
Tomar et al. (Tue,) studied this question.
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