A Novel Bi-Directional and Bi-Temporal Delivery System for Enhancing Intrasynovial Tendon Repair

Article A Novel Bi-Directional and Bi-Temporal Delivery System for Enhancing Intrasynovial Tendon Repair Yidan Chen 1,, Seth Kinoshita 2,, Emily Yan 3, Min Hao 3,, Hua Shen 4,, Richard Gelberman 4,, Stavros Thomopoulos 5,, and Younan Xia 2,3,*, 1 School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA 2 School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA 3 The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA 4 Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA 5 Department of Orthopedic Surgery, Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA * Correspondence: younan.xia@bme.gatech.edu Received: 24 September 2024; Revised: 8 October 2024; Accepted: 14 October 2024; Published: 18 October 2024 Abstract: Flexor tendon injuries are common and often require surgical repair and prolonged rehabilitation. Successful clinical outcomes depend on the concurrent suppression of adhesions (caused by inflammation) at the tendon surface and promotion of matrix synthesis inside the tendon. Herein, we report a bi-directional and bi-temporal drug delivery system designed to target both the initial inflammatory phase and the subsequent proliferative and remodeling phases of healing to improve outcomes after flexor tendon repair. The system features a multi-layered design with anti-adhesion and pro-matrix factors encapsulated in separate layers of hyaluronate films crosslinked to different degrees to control their direction and rate of release. After validating drug delivery under controlled release, cell culture experiments involving tendon fibroblasts and a Transwell system are conducted to demonstrate the system’s efficacy in modulating local cellular responses. The promising results from this study lay the groundwork for moving this system toward in vivo testing and clinical translation.