The Role of Polydeoxyribonucleotide as a Biotherapy for Musculoskeletal Disorders.

Polydeoxyribonucleotide (PDRN) is a DNA-derived biological therapy gaining prominence in the treatment of musculoskeletal disorders. It functions as an adenosine A2A receptor (A2AR) agonist and serves as a substrate in the nucleotide salvage pathway. These mechanisms drive anti-inflammatory effects, stimulate angiogenesis via vascular endothelial growth factor, and promote collagen synthesis. In osteoarthritis, PDRN reduces cartilage degradation and promotes the chondrogenic differentiation of stem cells. PDRN has shown therapeutic potential in tendinopathies, including Achilles and rotator cuff injuries, by supporting tissue repair. Preliminary reports suggest it may offer a non-steroidal alternative for managing spinal radiculopathy when corticosteroids are contraindicated, though robust comparative trials are needed. Preclinical and clinical evidence indicate favorable preliminary safety profiles and potential pain reduction. Future large-scale trials are needed to standardize the dosing protocols for integrated orthopedic rehabilitation.