Department of Orthopaedic Surgery, Konkuk University School of Medicine, 120-1 Neungdong-ro (Hwayang-dong), Gwangjin-gu, Seoul, 143-729, Korea.
Biot Korea Inc., 43-26 Chemdangwagi-ro 208 Beon-gil, Gwangju, 61001, Korea.
Sci Rep. 2024 Jul 31;14(1):17632. doi: 10.1038/s41598-024-67572-y.
Structural failure is a well-established complication of rotator cuff repair procedures. To evaluate the effect of magnetic microbeads, designed for precise drug delivery via magnetic force, on sustained transforming growth factor-beta-1 (TGF-β1) release and rotator cuff healing in a rat rotator cuff repair model. TGF-β1 laden microbeads were prepared, and baseline in vitro experiments included the magnetization of the microbeads and TGF-β1 release tests. In an in vivo experiment using a rat rotator cuff repair model on both shoulders, 72 rats were randomly assigned to three groups (24 per group): group A, conventional repair; group B, repair with and simple TGF-β1 injection; and group C, repair with magnet insertion into the humeral head and TGF-β1 laden microbead injection. Delivery of TGF-β1 was evaluated at 1 and 7 days after the intervention using PCR, Western blot, and immunohistochemistry. At 6 weeks post-intervention, rotator cuff healing was assessed using biomechanical and histological analysis. The in vitro experiments confirmed the magnetization property of the microbeads and sustained delivery of TGF-β1 for up to 10 days. No difference in the TGF-β1 expression was found at day 1 in vivo. However, at day 7, group C exhibited a significantly elevated expression of TGF-β1 in both PCR and Western blot analyses compared to groups A and B (all P < 0.05). Immunohistochemical analysis revealed a higher expression of TGF-β1 at the repair site in group C on day 7. At 6 weeks, biomechanical analysis demonstrated a significantly higher ultimate failure load in group C than in groups A and B (P < 0.05) and greater stiffness than in group A (P = 0.045). In addition, histological analysis showed denser and more regular collagen fibers with complete continuity to the bone in group C than in groups A and B, a statistically significant difference according to the semi-quantitative scoring system (all P < 0.05). The use of the TGF-β1 laden magnetic microbeads demonstrated sustained delivery of TGF-β1 to the repair site, improving rotator cuff healing.
结构失效是肩袖修复术常见的并发症。本研究旨在评估磁微球在大鼠肩袖修复模型中通过磁力精确药物输送对持续转化生长因子-β1（TGF-β1）释放和肩袖愈合的影响。制备负载 TGF-β1 的微球，并进行体外实验，包括微球的磁化和 TGF-β1 释放试验。在一项使用大鼠肩袖修复模型的体内实验中，将 72 只大鼠随机分为三组（每组 24 只）：A 组，常规修复；B 组，修复联合 TGF-β1 注射；C 组，修复联合肱骨头插入磁体和 TGF-β1 负载微球注射。干预后 1 天和 7 天通过 PCR、Western blot 和免疫组化评估 TGF-β1 的递送。干预后 6 周，通过生物力学和组织学分析评估肩袖愈合情况。体外实验证实了微球的磁化特性和 TGF-β1 的持续释放，可达 10 天。体内第 1 天，TGF-β1 表达无差异。然而，第 7 天，C 组在 PCR 和 Western blot 分析中 TGF-β1 的表达均明显高于 A 组和 B 组（均 P<0.05）。免疫组化分析显示第 7 天 C 组修复部位 TGF-β1 表达更高。6 周时，生物力学分析显示 C 组的最终失效负荷明显高于 A 组和 B 组（P<0.05），且比 A 组更硬（P=0.045）。此外，组织学分析显示 C 组胶原纤维更密集、更规则，与骨完全连续，根据半定量评分系统有统计学意义（均 P<0.05）。负载 TGF-β1 的磁微球的使用证明了 TGF-β1 持续输送到修复部位，改善了肩袖愈合。
