journal article·2025-10-31Open access

Nucleic Acid-Based Therapeutics for Periodontal Tissue Regeneration: A Comprehensive Review

Jwa-Young Kim, Min-Ho Hong, Seong-Gon Kim, Umberto Garagiola

Applied Sciences· Volume 15· Issue 21

Abstract

Polydeoxyribonucleotides (PDRNs) and polynucleotides (PNs) are biologically active DNA-derived polymers with emerging applications in regenerative dentistry. Acting through adenosine A2A receptor activation and modulation of inflammatory responses, these biomolecules promote angiogenesis, enhance fibroblast proliferation, and stimulate extracellular matrix synthesis. In periodontal therapy, their potential to accelerate healing, reduce inflammation, and support the regeneration of gingival connective tissue, periodontal ligament, cementum, and alveolar bone is of increasing clinical interest. This review synthesizes current preclinical and clinical evidence regarding the use of PDRNs and PNs for tissue regeneration in dentistry, including their mechanisms of action, delivery strategies, synergistic effects with biomaterials and growth factors, and safety profile. Furthermore, recent advances in injectable formulations, scaffold integration, and combined therapies are discussed. The review also highlights gaps in evidence, methodological limitations in existing studies, and future research directions needed to establish standardized treatment protocols. A total of 21 studies (10 PDRNs and 11 PNs/ODNs) were analyzed. PDRNs and PNs consistently demonstrated preclinical regenerative efficacy, although robust clinical validation remains limited.
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Research context

OpenAlex topics: Adenosine and Purinergic Signaling · Oral microbiology and periodontitis research · Oral and gingival health research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Oral and Maxillofacial Surgery, Hallym University Kangnam Sacred Heart Hospital, Hallym University Medical Center, 1 Singil-ro, Yeongdeungpo-gu, Seoul 07441, Republic of Korea

Department of Dental Biomaterials, Research Institute of Oral Science, College of Dentistry, Gangneung-Wonju National University, 7 Jukheon-gil, Gangneung-si 25457, Republic of Korea

Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, 7 Jukheon-gil, Gangneung-si 25457, Republic of Korea

Maxillofacial and Dental Unit, Biomedical, Surgical and Oral Sciences Department, School of Dentistry, University of Milan, 20122 Milan, Italy

Funding

Ministry of Education (MOE) and the Gangwon State (G.S.), Republic of Korea · Regional Anchor company-Academia Partnership Innovation Development

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