Background:The tendon-bone interface (TBI) in the rotator cuff has a poor intrinsic capacity for healing, which increases the risk of retear after rotator cuff repair (RCR). However, facilitating regeneration of the TBI still remains a great clinical challenge. Herein, the authors established a novel strategy based on magnetic seeding to enhance the TBI regeneration.Hypothesis:Magnetic seeding bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide (SPIO-BMSCs) into a biphasic scaffold can promote tendon-bone healing after RCR.Study Design:Controlled laboratory study.Methods:BMSCs were labeled with SPIOs. Prussian blue staining, CCK-8 tests, Western blot, and quantitative reverse transcription polymerase chain reaction (PCR) were used to determine the optimal effect concentration of SPIOs on cell bioactivities and abilities. Then SPIO-BMSCs were magnetically seeded into a biphasic scaffold under a magnetic field. The seeding efficacy was assessed by a scanning electron microscope, and the potential mechanism in chondrogenic differentiation after seeding SPIO-BMSCs into the scaffold was evaluated by Western blot and PCR. Furthermore, the effect of SPIO-BMSC/biphasic scaffold on tendon-bone healing after RCR using a rat model was examined using histological analysis, enzyme-linked immunosorbent assay, and biomechanical evaluation.Results:BMSCs labeled with 100 μg/mL SPIO had no effect on cell bioactivities and the ability of chondrogenic differentiation. SPIO-BMSCs were magnetically seeded into a biphasic scaffold, which offered a high seeding efficacy to enhance chondrogenic differentiation of SPIO-BMSCs via the CDR1as/miR-7/FGF2 pathway for TBI formation in vitro. Furthermore, in vivo application of the biphasic scaffold with magnetically seeded SPIO-BMSCs showed their regenerative potential, indicating that they could significantly accelerate and promote TBI healing with superior biomechanical properties after RCR in a rat rotator cuff tear model.Conclusion:Magnetically seeding SPIO-BMSCs into a biphasic scaffold enhanced seeding efficacy to promote cell distribution and condensation. This construct enhanced the chondrogenesis process via the CDR1as/miR-7/FGF2 pathway and further promoted tendon-bone healing after RCR in a rat rotator cuff tear model.Clinical Relevance:This study provides an alternative strategy for improving TBI healing after RCR.

中文翻译：

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SPIO-BMSCs 磁力播种到双相支架中可以促进肩袖修复后的肌腱骨愈合

背景：肩袖中的腱骨界面（TBI）固有的愈合能力较差，这增加了肩袖修复（RCR）后撕裂的风险。然而，促进 TBI 再生仍然是一个巨大的临床挑战。在此，作者建立了一种基于磁力播种的新策略来增强 TBI 再生。假设：将超顺磁性氧化铁标记的骨髓间充质干细胞 (SPIO-BMSCs) 磁力播种到双相支架中可以促进 RCR 后腱骨愈合。研究设计：对照实验室研究。方法：用SPIO标记BMSC。采用普鲁士蓝染色、CCK-8测试、Western blot和定量逆转录聚合酶链反应（PCR）确定SPIOs对细胞生物活性和能力的最佳作用浓度。然后，SPIO-BMSC 在磁场下被磁力接种到双相支架中。通过扫描电子显微镜评估接种效果，并通过蛋白质印迹和PCR评估将SPIO-BMSCs接种到支架后软骨分化的潜在机制。此外，通过组织学分析、酶联免疫吸附测定和生物力学评估，研究了 SPIO-BMSC/双相支架对大鼠 RCR 后肌腱骨愈合的影响。结果：用 100 μg/mL SPIO 标记的 BMSC 没有对细胞生物活性和软骨分化能力的影响。 SPIO-BMSCs被磁力接种到双相支架中，这提供了高接种效率，通过CDR1as/miR-7/FGF2途径增强SPIO-BMSCs的软骨分化，从而在体外形成TBI。此外，在体内应用磁力播种 SPIO-BMSC 的双相支架显示出其再生潜力，表明它们可以在大鼠肩袖撕裂模型中的 RCR 后显着加速和促进 TBI 愈合，并具有优异的生物力学特性。结论：磁力播种 SPIO- BMSCs 进入双相支架增强了接种功效，促进细胞分布和凝聚。该构建体通过 CDR1as/miR-7/FGF2 途径增强软骨形成过程，并在大鼠肩袖撕裂模型中进一步促进 RCR 后肌腱骨愈合。 临床意义：本研究为改善 RCR 后 TBI 愈合提供了另一种策略。