Aidan Barrera

Introduction: Rotator cuff tears are one of the most common musculoskeletal injuries encountered with about 250,000 rotator cuff repairs occurring annually.¹ The incidence rate of having a rotator cuff tear increases with age, while the success rate of healed injury decreases with age.² In rotator cuff injuries there is damage to the tendon-bone junction (enthesis) which is made up of cartilage, a transitional fibrocartilage, and bone.³ However, even with surgical reattachment, the enthesis, more specifically the transitional fibrocartilage, does not completely regenerate. Without a functional fibrocartilage zone, the repair site is prone to high stress and subsequent retear.³ Kartogenin (KGN) is a molecule of interest that has shown potential in the field of tissue engineering and was further explored with different scaffolds to see if it could induce the formation of fibrocartilage at the enthesis. Methods: Multiple studies examined the effect of KGN in vivo and in vitro. KGN was injected into an intact rat patellar tendon and an injured rat Achilles tendon for in vivo experimentation.³ KGN-PRP was examined in an experimentally injured rat Achilles tendon via surgical cut of the tendon and subsequent reattachment into a bone tunnel.⁴ KGN-fibrin glue was injected into a rabbit rotator cuff injury model. ⁵ These studies then performed immunohistochemical, biomechanical, and histomorphometric analysis. Results: In vivo experimentation showed increased amounts of proteoglycan synthesis in both the intact rat patellar tendon and the injured rat Achilles tendon.³ KGN-PRP showed increased expression of collagen I and II as well as organized collagen fiber bundles.^4,6  KGN-Fibrin Glue showed increased Tenascin C and Sox-9 expression, increased biomechanical strength, and organized collagen fibers indicative of proliferation of fibrocartilage.⁵ Conclusion: KGN has shown the ability to induce fibrocartilage formation at the enthesis in both in vitro and in vivo models. KGN is effective with different cell-free scaffolds, making its use in a clinical setting easier. KGN could be used in conjunction with the current surgical treatment of large rotator cuff tears as well as a nonsurgical treatment option for smaller tears or patients who are not good surgical candidates.

1. Agha O, Diaz A, Davies M, Kim HT, Liu X, Feeley BT. Rotator cuff tear degeneration and the role of fibro-adipogenic progenitors. Ann N Y Acad Sci. 2021;1490(1):13-28. doi:10.1111/NYAS.14437
2. Keener JD, Patterson BM, Orvets N, Chamberlain AM. Degenerative Rotator Cuff Tears: Refining Surgical Indications Based on Natural History Data. J Am Acad Orthop Surg. 2019;27(5):156. doi:10.5435/JAAOS-D-17-00480
3. Zhang J, Wang JHC. Kartogenin induces cartilage-like tissue formation in tendon–bone junction. Bone Research. 2014;2:14008. doi:10.1038/BONERES.2014.8
4. Zhou Y, Zhang J, Yang J, et al. Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon–bone interface. Journal of Tissue Engineering and Regenerative Medicine. 2017;11(12):3445-3456. doi:10.1002/TERM.2258
5. Zhu J, Shao J, Chen Y, et al. Fibrin glue-kartogenin complex promotes the regeneration of the tendon-bone interface in rotator cuff injury. Stem Cells International. 2021;2021. doi:10.1155/2021/6640424
6. Zhang J, Yuan T, Zheng N, Zhou Y, Hogan M v., Wang JHC. The combined use of kartogenin and platelet-rich plasma promotes fibrocartilage formation in the wounded rat Achilles tendon entheses. Bone and Joint Research. 2017;6(4):231-244. doi:10.1302/2046-3758.64.BJR-2017-0268.R1/ASSET/IMAGES/LARGE/10.1302_2046-3758.64.BJR-2017-0268.R1-FIG11.JPEG