Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study

This study aims to evaluate the effects of BPC-157, synthetic thymosin beta-4 (TB-500), and their combination on Achilles tendon healing using biomechanical, histopathological, histochemical, and immunohistochemical analyses in a rat model.

Thirty-two male Sprague-Dawley rats, each aged 12 weeks and weighing approximately 330 g, underwent standardized Achilles tendon transection and repair and were randomly assigned to four groups, with eight rats in each group: control, BPC-157 (10 µg/kg/day), TB-500 (60 µg/kg/day), and combined BPC-157 + TB-500 (BPC + TB). Treatments were administered intraperitoneally for four weeks postoperatively. At four weeks, tendons were harvested for biomechanical testing or histological evaluation. Maximum load to failure was assessed biomechanically. Histological and histochemical analyses included hematoxylin-eosin, Masson trichrome, Alcian blue, and Sirius red staining and were evaluated using Bonar and Movin scoring systems. Expression of collagen types I and III was assessed immunohistochemically and semiquantified using H-score analysis.

Biomechanical testing revealed higher maximum load to failure values in the BPC-157 and TB-500 groups compared to controls, reaching statistical significance in the TB-500 group (p < 0.05). Histopathological evaluation demonstrated significantly lower total Bonar scores in the TB-500 group (p = 0.016) and significantly lower total Movin scores in the TB-500 and BPC + TB groups (p = 0.017 and p = 0.040, respectively) relative to controls, indicating improved tendon architecture, collagen alignment, and reduced degenerative changes. The BPC-157 group showed numerically lower scores without reaching statistical significance for total scores. Sirius red birefringence analysis showed increased type I collagen organization and altered type III collagen distribution in treatment groups, particularly in the TB-500 group, suggesting progression toward matrix maturation. Immunohistochemical analysis revealed no significant differences in collagen type I expression among groups, whereas collagen type III expression differed significantly, consistent with histochemical findings. Combined BPC-157 and TB-500 treatment did not confer additional benefits compared to either agent alone.

In this exploratory rat model study, both BPC-157 and TB-500 were associated with improved histopathological parameters and extracellular matrix organization during early Achilles tendon repair, with TB-500 additionally demonstrating a significant biomechanical advantage at four weeks. The absence of additive effects with combination therapy may reflect convergence on shared downstream pathways; however, this hypothesis requires further experimental confirmation. These preliminary findings indicate that both peptides warrant further investigation as candidate adjuncts to tendon repair, pending dose-optimization and longer-term studies.