Using Deferoxamine to Improve Soft Tissue Regeneration following Achilles Tendon Repair
Introduction. The Achilles tendon is the strongest tendon in the body and facilitates walking, running, and jumping movements.1 Despite its strength, the incidence of Achilles tear has reached approximately 8.3 ruptures per 100,000 people over the last several years due to increased participation in recreational activities.2 Surgical management is required for tendon repair, but post-repair function is significantly compromised as indicated by the 30% reduction in tendon tensile strength after surgery.1,3 This reduction in post-repair function can be attributed to the hypovascularity at the tendon midsection. Hypovascularity creates a nutritionally deficient environment which increases susceptibility to ruptures and surgical complications.3,4 Studies have shown using Deferoxamine (DFO) in healing environments prolongs availability of HIF-1a and VEGF thereby increasing angiogenesis and Type I collagen formation.5,6 Applied to the Achilles tendon, DFO has the potential ultimately to improve tendon strength after surgery.3 Methods. Nine broiler hens were separated into a control (CTL) group and deferoxamine (DFO) group. For each hen, the right Achilles tendon was partially severed at the hypovascular midsection and surgically repaired. Hens in CTL group were treated with 3-0 Vicryl suture soaked in water. Hens in DFO group were treated with 3-0 Vicryl suture soaked in 324 mM DFO solution. Animals were euthanized after two weeks, and each Achilles tendon was harvested to evaluate (1)angiogenesis via hemoglobin content and vessel density and (2)tissue repair via proteoglycan (PG) and DNA content.3 Results. Hemoglobin content was increased in DFO group (0.081 ± 0.012, P = .046) compared with CTL group (0.063 ± 0.016; P = .046). PG content was decreased in DFO group (0.26 ± 0.02; P = .035) compared with the CTL group (0.33 ± 0.08; P = .035). Articular zone vessel density (vessels/mm2) was increased in DFO group (7.1 ± 2.5; P = .026) compared with CTL group (2.1 ± 0.9; P = .026).3 Conclusions. Significant increases in hemoglobin content and articular zone vessel density in the DFO group compared to CTL indicate increased angiogenesis in the Achilles tendons repaired with DFO sutures. Additionally, the DFO group showed greater level of DNA and lower level of PG, suggesting improved early healing by fibrous tissue formation.3 These results support the hypothesis that DFO could be used to improve tendon healing following surgical repair of the Achilles. Further studies, however, are needed in larger animal models and human trials to verify its efficacy in a surgical setting.
- Yang X, Meng H, Quan Q, Peng J, Lu S, Wang A. Management of acute Achilles tendon ruptures: A review. Bone Joint Res. 2018;7(10):561-569. Published 2018 Nov 3. doi:10.1302/2046-3758.710.BJR-2018-0004.R2
- Suchak AA, Bostick G, Reid D, Blitz S, Jomha N. The incidence of Achilles tendon ruptures in Edmonton, Canada. Foot Ankle Int. 2005;26(11):932-936. doi:10.1177/107110070502601106
- Efird WM, Fletcher AG, Draeger RW, Spang JT, Dahners LE, Weinhold PS. Deferoxamine-Soaked Suture Improves Angiogenesis and Repair Potential After Acute Injury of the Chicken Achilles Tendon. Orthopaedic Journal of Sports Medicine. October 2018. doi:10.1177/2325967118802792
- Chen TM, Rozen WM, Pan WR, Ashton MW, Richardson MD, Taylor GI. The arterial anatomy of the Achilles tendon: anatomical study and clinical implications. Clin Anat. 2009 Apr;22(3):377-85. doi: 10.1002/ca.20758. PMID: 19173244.
- D. Tang JB, Wu YF, Cao Y, et al. Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons. Sci Rep. 2016;6:20643. Published 2016 Feb 11. doi:10.1038/srep20643
- Wahl EA, Schenck TL, Machens HG, Balmayor ER. VEGF released by deferoxamine preconditioned mesenchymal stem cells seeded on collagen-GAG substrates enhances neovascularization. Sci Rep. 2016;6:36879. Published 2016 Nov 10. doi:10.1038/srep36879