Suture materials and surgical knot tying techniques have improved dramatically since their first use over five millennia ago. However, the approach remains limited by the ability of the suture to transfer load to tissue at suture anchor points. Ths is especially problematic for repairs that require high strength such as tendon and ligament repairs, where repair-site elongation and rupture rates are as high as 94% for rotator cuff and 48% for flexor tendon. The goal of this proposal is to revolutionize suture repair technology by creating adhesive-coated sutures that distribute load transfer over the suture's length, leading to substantial improvements in surgical repair strength. Using mathematical models that define desirable adhesive material properties for improving tendon repair strength, the first aim of the study seeks to develop adhesive biomaterials with optimized mechanical properties to improve load distribution of tendon repairs. These novel bioadhesive materials will be created using a suite of tools to control both mechanical and chemical properties. Adhesive biomaterials will be applied to sutures and evaluated biomechanically in ex vivo flexor digitorum profundus tendons.
The second aim will evaluate biocompatibility of adhesive biomaterials that provide at least a 30% improvement in ex vivo repair strength. Biocompatibility will be assessed via cell- and tissue-level responses to the bioadhesives after co- culturing primary tendon fibroblasts with the adhesive biomaterials in vitro, as well as implanting the adhesive biomaterials subcutaneously in an in vivo animal model. After establishing the ex vivo mechanical efficacy and in vivo biocompatibility, the third aim will determine efficacy of adhesive sutures for improved outcomes after in vivo tendon repairs in a preclinical surgical study. Fully trained orthopedic surgeons wil apply this new technology in a clinically relevant, established large animal model for flexor tendon repair to assess surgical outcomes. This research will develop a novel suturing platform that fundamentally changes the mechanical principles of suture repairs, transforming this age-old technology to dramatically improve surgical repair strength. The proposed research will demonstrate the clinical utility of adhesive-coated sutures through preclinical studies that lay th foundation for clinical trials. This research has the potential to improve repair strength, enable more aggressive rehabilitation protocols, and decrease surgical repair failures for tendon and ligament reconstruction.
While there have been many improvements in suture materials and stitching techniques since sutures were first used over 5 millennia ago, the core technology of sewing tissues together remains a crude mechanical solution. Sutures are excellent tools for repairing many injuries; however, tendon and ligament repairs have high repair-site failure rates due to the high strength demands to accommodate activities of daily living. The proposed research lays the foundation for a paradigm-shift in suture repairs by developing adhesive-coated sutures that distribute load transfer along the suture's length, leading to dramatic repair strength improvements that promise to decrease orthopedic surgery failure rates.
| Linderman, Stephen W; Shen, Hua; Yoneda, Susumu et al. (2018) Effect of connective tissue growth factor delivered via porous sutures on the proliferative stage of intrasynovial tendon repair. J Orthop Res 36:2052-2063 |
| Linderman, Stephen W; Golman, Mikhail; Gardner, Thomas R et al. (2018) Enhanced tendon-to-bone repair through adhesive films. Acta Biomater 70:165-176 |
| Gelberman, Richard H; Linderman, Stephen W; Jayaram, Rohith et al. (2017) Combined Administration of ASCs and BMP-12 Promotes an M2 Macrophage Phenotype and Enhances Tendon Healing. Clin Orthop Relat Res 475:2318-2331 |
| Linderman, Stephen W; Gelberman, Richard H; Thomopoulos, Stavros et al. (2016) Cell and Biologic-Based Treatment of Flexor Tendon Injuries. Oper Tech Orthop 26:206-215 |
| Shen, Hua; Kormpakis, Ioannis; Havlioglu, Necat et al. (2016) The effect of mesenchymal stromal cell sheets on the inflammatory stage of flexor tendon healing. Stem Cell Res Ther 7:144 |
| Kormpakis, Ioannis; Linderman, Stephen W; Thomopoulos, Stavros et al. (2016) Enhanced Zone II Flexor Tendon Repair through a New Half Hitch Loop Suture Configuration. PLoS One 11:e0153822 |
| Li, Jianhua; Linderman, Stephen W; Zhu, Chunlei et al. (2016) Surgical Sutures with Porous Sheaths for the Sustained Release of Growth Factors. Adv Mater 28:4620-4 |
