Summary
Polynucleotide could be more suitable for combined therapy with platelet rich plasma than polydeoxyribonucleotide to escape a negative feedback because of different timing of growth factors’ surges.
Abstract
Introduction
Platelet rich plasma (PRP), polydeoxyribonucleotide (PDRN) and polynucleotide (PN) have been recently used for enhancing the healing of various tissues with their mechanism associated growth factors. This study was performed to explore the effect of PDRN and PN combined with PRP on tendon healing and reversal of fatty degeneration in a chronic rotator cuff tear model using a rat infraspinatus.
Materials And Methods
Fifty six SD male rats were randomly assigned to four groups (14 rats per group: 6 for histological evaluation and 8 for mechanical and blood testing): saline+repair: G1, PRP+repair: G2, PRP+PDRN+repair: G3, and PRP+PN+repair: G4. The right shoulder was used for experimental interventions, and the left served as a control. Four weeks after detaching the infraspinatus, the torn tendon was repaired. Saline, PDRN, and PN were applied to the repair sites. And 2 weeks after repair, same materials were injected, again. Histological and mechanical evaluation was performed at 4 weeks after repair and blood analysis on vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF) was performed using the rats for the mechanical testing at the surgery or repair, 2 and 4 weeks.
Results
The mean load-to-failures of right shoulders were not statistically significant different from those of left shoulder only in G3 and G4 groups (p=.200 and p=.068). There were no significant differences in the number of fat cells and in the parallel orientation of collagen fiber on tendon to bone junction between G4 and sham groups (p=.317). Among the right shoulders of G1 to 4, G2 to 4 showed a smaller numbers of fat cells on H&E and oil red O stain than G1 (p=.040, p=.040, and p=.022, each). G4 showed a more CD68 stained macrophages than G1 and G2 (p=.023 and p=.026). The ratio of CD68/CD168 stained cell showed significant differences between G1 and G2, G1 and G4, and G2 and G4 (p=.043, p=.021, and p=021). G4 showed a higher cellularity than G1 (p=.040). The mean plasma VEGF at 4 weeks after repair showed significant differences between G1 and G4, and G3 and G4 (p=.006 and p=.025). The mean plasma FGF at 4 weeks after repair showed significant differences between G1 and G2, G1 and G3, G1 and G4, and G3 and G4 (p=.030, p=.035, p=.003 and p=.025).
Conclusion
PDRN and PN combined with PRP might have possibility to improve tendon healing and decrease fatty degeneration after repair of chronic rotator cuff tear. However, there could be a negative feedback between PRP and PDRN which might not show a synergistic effect due to already abundant growth factors. On the other hand, there could be a synergistic effect between PRP and PN because of different timing of growth factors’ surges. Therefore, PN could be more suitable for combined therapy with PRP than PDRN to escape a negative feedback.