Sustained Release of Amnion-Derived Cellular Cytokine Solution Facilitates Achilles Tendon Healing in Rats

Objective: In the United States, around 50% of all musculoskeletal injuries are soft tissue injuries including ligaments and tendons. The objective of this study is to assess the role of amnion-derived cellular cytokine solution (ACCS) in carboxy-methyl cellulose (CMC) gel in the healing of Achilles tendon in a rat model, and to examine its effects on mechanical properties and collagen content. Methods: Achilles tendons of Sprague-Dawley rats were exposed and transected. The distal and proximal ends were injected with either saline or ACCS in CMC, in a standardized fashion, and then sutured using a Kessler technique. Tendons from both groups were collected at 1, 2, 4, 6, and 8 weeks postoperatively and assessed for material properties. Collagen studies were performed, including collagen content, collagen cross-linking, tendon hydration, and immunohistochemistry. Tendons were also evaluated histologically for cross-sectional area. Results: Mechanical testing demonstrated that treatment with ACCS in CMC significantly enhances breaking strength, ultimate tensile strength, yield strength, and Young's modulus in the tendon repair at early time points. In context, collagen content, as well as collagen cross-linking, was also significantly affected by the treatment. Conclusion: The application of ACCS in CMC has a positive effect on healing tendons by improving mechanical properties at early time points. Previous studies on onetime application of ACCS (not in CMC) did not show significant improvement on tendon healing at any time point. Therefore, the delivery in a slow release media like CMC seems to be essential for the effects of ACCS demonstrated in this study.