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

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jun Zhu ◽  
Jiahua Shao ◽  
Yi Chen ◽  
Guangyi Zhao ◽  
Lexiang Li ◽  
...  

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.

2016 ◽  
Vol 4 (7_suppl4) ◽  
pp. 2325967116S0014
Author(s):  
Ryan Degen ◽  
Andrew Carbone ◽  
Camilia Carballo ◽  
Jianchun Zong ◽  
Tony Chen ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji-Hye Yea ◽  
Jin-Kyung Park ◽  
In Ja Kim ◽  
Gayoung Sym ◽  
Tae-Soo Bae ◽  
...  

Abstract Background It is difficult to immediately use mesenchymal stem cells (MSCs) for the patient with rotator cuff disease because isolation and culture time are required. Thus, the MSCs would be prepared in advanced in cryopreserved condition for an “off-the-shelf” usage in clinic. This study investigated the efficacy of freshly thawed MSCs on the regeneration of a full-thickness tendon defect (FTD) of rotator cuff tendon in a rat model. Methods We evaluated morphology, viability, and proliferation of cultured umbilical cord-derived MSCs (C-UC MSCs) and freshly thawed umbilical cord-derived MSCs (T-UC MSCs) at passage 10 in vitro. In animal experiments, we created a FTD in the supraspinatus of rats and injected the injured tendon with saline, cryopreserved agent (CPA; control), C-UC MSCs, and T-UC MSCs, respectively. Two and 4 weeks later, macroscopic, histological, biomechanical, and cell trafficking were evaluated. T test and ANOVA were used with SPSS. Differences with p < .05 were considered statistically significant. Results T-UC MSCs had fibroblast-like morphology and showed greater than 97% viability and stable proliferation comparable to the C-UC MSCs at passage 10. In animal experiments, compared with the control group, the macroscopic appearance of the T-UC MSCs was more recovered at 2 and 4 weeks such as inflammation, defect size, neighboring tendon, swelling/redness, the connecting surrounding tissue and slidability. Histologically, the nuclear aspect ratio, orientation angle of fibroblasts, collagen organization, and fiber coherence were improved by 33.33%, 42.75%, 1.86-fold, and 1.99-fold at 4 weeks, and GAG-rich area decreased by 88.13% and 94.70% at 2 and 4 weeks respectively. Further, the T-UC MSCs showed enhanced ultimate failure load by 1.55- and 1.25-fold compared with the control group at both 2 and 4 weeks. All the improved values of T-UC MSCs were comparable to those of C-UC MSCs. Moreover, T-UC MSCs remained 8.77% at 4 weeks after injury, and there was no significant difference between C-UC MSCs and T-UC MSCs. Conclusions The morphology, viability, and proliferation of T-UC MSCs were comparable to those of C-UC MSCs. Treatment with T-UC MSCs could induce tendon regeneration of FTD at the macroscopic, histological, and biomechanical levels comparable to treatment with C-UC MSCs.


2015 ◽  
Vol 39 (6) ◽  
pp. 1219-1225 ◽  
Author(s):  
Philippe Hernigou ◽  
Guillaume Merouse ◽  
Pascal Duffiet ◽  
Nathalie Chevalier ◽  
Helene Rouard

2020 ◽  
Author(s):  
Ji-Hye Yea ◽  
Jin-Kyung Park ◽  
InJa Kim ◽  
Gayoung Sym ◽  
Tae Soo Bae ◽  
...  

Abstract Background: It is difficult to immediately use mesenchymal stem cells (MSCs) for the patient with rotator cuff disease because isolation and culture time are required. Thus, the MSCs would be prepared in advanced in cryopreserved condition for an “off-the-shelf” usage in clinic. This study investigated the efficacy of freshly thawed MSCs on the regeneration of a full-thickness tendon defect (FTD) of rotator cuff tendon in a rat model. Methods: We evaluated morphology, viability and proliferation of cultured umbilical cord-derived MSCs (C-UC MSCs) and freshly thawed umbilical cord-derived MSCs (T-UC MSCs) at passage 10 in vitro. In animal experiments, we created a FTD in the supraspinatus tendon of rats and injected the injured tendon with saline, cryopreserved agent (CPA; control), C-UC MSCs, and T-UC MSCs respectively. Two to four weeks later, macroscopic, histological and biomechanical changes were evaluated. T-test and ANOVA were used with SPSS. Differences with p < .05 were considered statistically significant.Results: T-UC MSCs had fibroblast-like morphology and showed greater than 97% viability and stable proliferation comparable to the C-UC MSCs at passage 10. In animal experiments, compared with the control group, the macroscopic appearance of the T-UC MSCs was further recovered at two and four weeks such as inflammation, defect size, neighboring tendon, swelling/redness and the connecting surrounding tissue and slidability. Histologically, compared to the control group the nuclear aspect ratio, orientation angle of fibroblasts, collagen organization and fiber coherence were improved by 33.33%, 42.75%, 1.86- and 1.99-fold and GAG-rich area was suppressed by 81.05% at four weeks. Further, the T-UC MSCs showed enhanced ultimate failure load by 1.55- and 1.25-fold compared with the control group at both two and four weeks. All the improved values of T-UC MSCs were comparable to those of C-UC MSCs. Conclusions: The morphology, viability and proliferation of T-UC MSCs are comparable to those of C-UC MSCs. Treatment with T-UC MSCs induces tendon regeneration of FTD at the macroscopic, histological and biomechanical levels comparable to treatment with C-UC MSCs.


Author(s):  
Girotti Alessandra ◽  
Iba�ez Arturo ◽  
Trigueros Larrea Jos� Mar�a ◽  
Lamus Molina Jos� Francisco ◽  
Alonso Matilde ◽  
...  

2018 ◽  
Vol 27 (11) ◽  
pp. 1613-1622 ◽  
Author(s):  
Dong Rak Kwon ◽  
Gi-Young Park ◽  
Yong Suk Moon ◽  
Sang Chul Lee

While therapies using mesenchymal stem cells (MSCs) to treat rotator cuff tendon tear (RCTT) have yielded some promising preliminary results, MSCs therapy has not yet completely regenerated full-thickness RCTT (FTRCTT). It has recently been reported that polydeoxyribonucleotide (PDRN) is effective in the treatment of chronic rotator cuff disease. We hypothesized that local injection of human umbilical cord blood-derived (UCB)–MSCs with PDRN would be more effective in regenerating tendon tear than UCB-MSCs alone. The purpose of this study was to evaluate the effects of UCB–MSCs combined with different doses of PDRN on the regeneration of RCTT in a chronic RCTT model by using a rabbit model. New Zealand white rabbits ( n = 24) with FTRCTT were allocated randomly into three groups (8 rabbits per group). Three different injectants (G1-S, 0.2 mL UCB-MSCs; G2-P1, 0.2 mL UCB-MSCs with one injection of 0.2 mL PDRN; G3-P4, 0.2 mL UCB-MSCs, and four injections of 0.2 mL PDRN per week) were injected into FTRCTT under US-guidance. After the rabbits were euthanized, we evaluated ross morphological and histological change. Motion analysis was also performed. There were significant differences in gross morphological changes between before, and at 4 weeks after injection, in all three groups, but no differences were found among the three groups. Masson’s trichrome (MT) or anti-type 1 collagen antibody (COL-1)-positive cell densities in G2-P1 and G3-P4 were improved significantly compared with those in G1-S, but showed no significant difference between G2-P1 and G3-P4. On motion analysis, walking distance and fast walking time in G2-P1 and G3-P4 were significantly longer/higher than those in G1-S, but showed no significant differences between G2-P1 and G3-P4. These results demonstrated that there was no significant difference in the gross morphologic change of tendon tear between UCB-MSCs only and combination with PDRN injection in rabbit model of chronic traumatic FTRCTT. Furthermore, there were no significant differences in the regenerative effects between high and low doses of (0.8 and 0.2) mL of PDRN.


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