Comparison of tendon healing using local platelet-rich plasma, erythropoietin, and erythropoietin-bevacizumab in a rat achilles tenotomy model

Abstract

Objectives: This study aims to evaluate the effects of platelet-rich plasma (PRP), erythropoietin (EPO), and EPO-bevacizumab (EPO-BEVA) combination on tendon healing in a rat Achilles tenotomy model. Materials and methods: Fifty-six male Wistar albino rats (14 to 16 weeks old) were randomly assigned to control, PRP, EPO, and EPO-BEVA groups including 14 rats in each group. Bilateral Achilles tenotomy was performed under anesthesia, followed by respective treatments. Platelet-rich plasma (0.1 mL/tendon) was prepared using a Ficoll-based extraction kit. The EPO (500 U/kg) and EPO-BEVA (175 U EPO + 1.25 mg BEVA) were administered locally. Biomechanical analysis assessed maximum force, stiffness, tensile stress, and Young's modulus. Histological evaluation included Bonar scoring, collagen organization, tenocyte morphology, and vascularity. Cross-sectional area (CSA) was measured. Results: At Week 2, the EPO-BEVA group exhibited superior stiffness (14.79 +/- 6.9 N/mm) than PRP (8.64 +/- 1.5 N/mm, p=0.015) and greater tensile stress (8.2 +/- 1 MPa) than control (6.16 +/- 1.3 MPa, p=0.031). The CSA was reduced (4.79 +/- 0.8 mm2) compared to EPO (6.56 +/- 1.1 mm2, p=0.038), indicating qualitative tendon improvements. Histological analysis showed enhanced matrix organization and reduced vascularity in the EPO-BEVA group, with lower Bonar scores (5.29 +/- 1.4 vs. 9.29 +/- 1.1 in control, p=0.002). By Week 4, maximum force remained higher in EPO-BEVA (46.67 +/- 5.8 N) than control (34.84 +/- 3 N, p=0.004), with sustained Young's modulus superiority compared to EPO (3.2 +/- 1.2 MPa vs. 1.78 +/- 0.5 MPa, p=0.014), although the stiffness differences were no longer significant. Conclusion: Our study results showed that EPO-BEVA enhanced tendon healing via vascular and matrix modulation, although the lack of a BEVA-only group limits conclusions on synergy. Future studies with larger sample sizes, including BEVA monotherapy, optimized dosing strategies, and long-term evaluations are needed to better clarify these effects and refine treatment strategies in regenerative medicine.