Fibrin Glue-Kartogenin Complex Promotes the Regeneration of the Tendon-Bone Interface in Rotator Cuff Injury.

Jun Zhu,Yiqin Zhou,Qiwei Fu,Qirong Qian,Jiahua Shao,Zheru Ding,Yi Chen,Guangyi Zhao,Qi Zhou,Lexiang Li,Jess Frith

doi:10.1155/2021/6640424

Jun Zhu, Yiqin Zhou + Show 9 more

Open Access

https://doi.org/10.1155/2021/6640424

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Abstract

Objective Rotator cuff injury healing is problematic because the tendon-bone junction often forms cicatricial tissues, rather than fibrocartilage, which leads to mechanical impairment and is prone to redamage. Kartogenin (KGN) is a newly discovered small molecule compound which can induce cartilage formation through chondrogenesis of endogenous mesenchymal stem cells. Methods In this study, we used KGN with fibrin glue (FG) to repair the rotator cuff injury by promoting the formation of fibrocartilage at the tendon to bone interface. Firstly, we assessed the release rate of KGN from the FG-KGN complex and then created a rabbit rotator cuff tendon graft-bone tunnel model. The rabbits received saline, FG-KGN, or FG injections onto the tendon to bone interface after injury. Shoulder tissues were harvested at 6 and 12 weeks, and the sections were stained with HE and Safranin O/Fast green. The samples were assessed by histologic evaluation and biomechanical testing. Synovial mesenchymal stem cells derived from the synovial tissue around the rotator cuff were harvested for western blotting and qRT-PCR analysis. Results KGN was released rapidly from the FG-KGN complex during first 4 hrs and followed by a slow release until 7 days. The tendon graft-bone interface in the control (saline) group and the FG group was filled with scar tissue, rather than cartilage-like tissue, and only a small number of chondrocytes were found at the adjacent bone surface. In the FG-KGN group, the tendon to bone interface was fully integrated and populated by chondrocytes with proteoglycan deposition, indicating the formation of fibrocartilage-like tissues. At 12 weeks, the maximum tensile strength of the FG-KGN group was significantly higher than that of the FG and control groups (P < 0.01). The RNA expression levels of tendinous genes such as Tenascin C and the chondrogenic gene Sox-9 were substantially elevated in SMSCs treated with the FG-KGN complex compared to the other two groups. Conclusion These results indicated that fibrin glue is an effective carrier for KGN, allowing for the sustained release of KGN. The FG-KGN complex could effectively promote the regeneration and formation of fibrocartilage tissue of the tendon-bone interface in the rabbit rotator cuff tendon graft-bone tunnel model.

Highlights

Rotator cuff injury is the most common cause of shoulder dysfunction in clinical patients, causing long-term pain and limited movement [1]
These results indicate that KGN is rapidly released from the fibrin glue (FG)-KGN complex within the first four hours, slowly released over the few days (Figure 1)
The qRT-PCR results indicate that the expression level of the tendinous gene Tenascin C was highly elevated in synovial mesenchymal stem cells (SMSCs) treated with the FG-KGN complex and was more than twofold compared to the other two groups (P < 0:01)

Summary

Introduction

Rotator cuff injury is the most common cause of shoulder dysfunction in clinical patients, causing long-term pain and limited movement [1]. The recurrence rate of rotator cuff tear after surgical reconstruction ranges from 20%~94% [1,2,3,4]. Pathological study shows that the tissue structure of the rotator cuff after reconstruction cannot be restored to the original composition [6, 7]. The main problem is that the fibrocartilage in the tendon graft-bone interface fails to regenerate and is replaced by scar tissue [5]. Its mechanical properties are impaired, which leads to deficient restoration of shoulder function and high recurrence rates of tendon-

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Conclusion