Polydeoxyribonucleotide (PDRN) - Established Efficacy and Emerging Directions in Research and Development -

Polydeoxyribonucleotide (PDRN), a biologically active mixture of deoxyribonucleic acid fragments, has demonstrated regenerative, anti-inflammatory, and anti-ischemic effects across diverse preclinical and clinical models. Mechanistically, PDRN exerts its therapeutic actions through adenosine A2A receptor activation, provision of nucleotide precursors for DNA synthesis, and modulation of inflammatory and angiogenic pathways, thereby promoting tissue repair in wounds, osteochondral defects, and degenerative skin conditions. Traditionally sourced from salmon testes, conventional PDRN formulations face challenges related to raw material stability, immunogenicity, production costs, and batch-to-batch variability. Recent advances in microbial fermentation using plant-derived lactic acid bacteria (LAB) offer a sustainable and safer alternative for PDRN production. Furthermore, PEGylation of PDRN (PEG-PDRN) has emerged as a promising strategy to enhance pharmacokinetic profiles, prolong systemic circulation, reduce immunogenicity, and improve formulation stability. Preclinical and clinical evidence supports the efficacy and safety of PDRN and PEG-PDRN in wound healing, angiogenesis, osteogenesis, and skin rejuvenation. Future research directions include optimization of PEGylated formulations, large-scale production using LAB platforms, exploration of combination therapies with growth factors or stem cells, and molecular-level elucidation of mechanisms. Collectively, plant-derived PEG-PDRN represents a next-generation regenerative therapy with translational potential for both medical and cosmetic applications.