Therapeutic Effects of Polydeoxyribonucleotide and Atelocollagen into Achilles Tendon Injury in a Rat Model.

Abstract

Background: Treatment of Achilles tendon injury varied from surgical to nonsurgical management, such as immobilization, step-by-step physical therapy, or injection with regenerative agents. Regenerative treatment has been studied using polydeoxyribonucleotide (PDRN), atelocollagen, prolotherapy, platelet-rich plasma, and mesenchymal stem cells. PDRN and atelocollagen monotherapy have been known to promote mitigation of fibroblasts, synthesis of collagen fibers, and secretion of growth factors for tissue remodeling.

Purpose: To compare the therapeutic effects of PDRN, atelocollagen, and PDRN + atelocollagen treatments in rats with a partial Achilles tendon injury.

Study design: Controlled laboratory study.

Methods: A total of 32 Sprague-Dawley rats, aged 8 weeks, were divided into 4 groups-normal saline, PDRN, atelocollagen, and PDRN + atelocollagen. The partial Achilles tendon injury was induced using punch biopsy tools. The treatment was administered 1 day after the injury. The biomechanical evaluation using load to failure and energy absorbed, histology related to inflammation and collagen fiber arrangement, and immunohistochemistry evaluation with collagen-I, transforming growth factor beta1, vascular endothelial growth factor (VEGF), and fibroblast growth factor were measured at 1 week and 4 weeks.

Results: The tensile strength test conducted at week 4 after injury measured a significantly higher energy absorbed in the PDRN + atelocollagen group than that in the control group. The hematoxylin and eosin (H&E) stain showed that neutrophil invasion was significantly higher in the control group compared with the other groups. Collagen fiber arrangement relatively increased in the atelocollagen and PDRN + atelocollagen groups. After 4 weeks, H&E in all groups showed decreased neutrophil invasion and lower inflammation index. Immunohistochemistry exhibited increased levels of collagen I in the PDRN group compared with the control group and an increased level of VEGF in the PDRN + atelocollagen group compared with the other groups at week 1. After 4 weeks, a high expression of collagen I, transforming growth factor beta1, and fibroblast growth factor was observed in the PDRN and PDRN + atelocollagen groups; the expression of VEGF showed an upward trend in the atelocollagen group compared with the PDRN + atelocollagen group.

Conclusion: The combined use of PDRN and atelocollagen resulted in increased energy absorbed by the repaired tendons and increased expression of healing growth factors in a partial tendon injury rat model. These benefits appear to be greater than the use of either agent alone. The combined use of PDRN and atelocollagen should be investigated in human patients with tendon injuries.

Clinical relevance: PDRN and atelocollagen are commonly used in patients with tendon injuries; however, the comparison of therapeutic effects or synergistic effects has not yet been studied.