Comparison of tendon healing using local platelet-rich plasma, erythropoietin, and erythropoietin-bevacizumab in a rat Achilles tenotomy model
Ahmet Emrah Açan1
, Aslı Karakılıç2, Mert Emre Aydın1, Özgür Bulmuş2, Emrah Özcan3, Gülay Turan4, Özge Özmen4, Reşit Buğra Hüsemoğlu5
1Department of Orthopedics and Traumatology, Balıkesir University Faculty of Medicine, Balıkesir, Türkiye
2Department of Physiology, Balıkesir University, Faculty of Medicine, Balıkesir, Türkiye
3Department of Anatomy, Balıkesir University, Faculty of Medicine, Balıkesir, Türkiye
4Department of Pathology, Balıkesir University, Faculty of Medicine, Balıkesir, Türkiye
5Department of Biomechanics, Dokuz Eylül University, Institute of Health Sciences, İzmir, Türkiye
Keywords: Bevacizumab, erythropoietin, platelet-rich plasma, tendon healing.
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.
Citation: Açan AE, Karakılıç A, Aydın ME, Bulmuş Ö, Özcan E, Turan G, et al. Comparison of tendon healing using local platelet-rich plasma, erythropoietin, and erythropoietin-bevacizumab in a rat Achilles tenotomy model. Jt Dis Relat Surg 2025;36(2):383-393. doi: 10.52312/jdrs.2025.2234.
Research design, Material preparation, interpretation of data, drafting the paper: A.E.A.; Analysis and acquisition of data, drafting the paper: K.A.; Material preparation and acquisition of data: A.M.E.; Revising it critically: B.Ö.; Analysis and acquisition of data: Ö.E.; Acquisition of data: T.G.; Acquisition of data: Ö.Ö.; Acquisition of data: H.R.B.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The authors received no financial support for the research and/or authorship of this article.
The statistics were performed by Prof. Sinan Saraçlı, Department of Biostatistics, Faculty of Medicine, Balıkesir University.
The data that support the findings of this study are available from the corresponding author upon reasonable request.