Local Injection of Rapamycin-Loaded Pcl-Peg Nanoparticles for Enhanced Tendon Healing in Rotator Cuff Tears via Simultaneously Reducing Fatty Infiltration and Drug Toxicity
Local Injection of Rapamycin-Loaded Pcl-Peg Nanoparticles for Enhanced Tendon Healing in Rotator Cuff Tears via Simultaneously Reducing Fatty Infiltration and Drug Toxicity
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DOI：
10.1002/adhm.202300612
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发表时间：
2023-11-16
影响因子：
10
通讯作者：
Hou，Jingyi
中科院分区：
文献类型：
--
作者：
Ye，Jichao;Wang，Yongbo;Hou，Jingyi
肩袖撕裂（RCT）是肩关节疼痛的常见原因，由于肌源性干细胞（MDSC）引起的脂肪浸润导致其预后不佳，因此临床上难以治疗。以往的研究发现，雷帕霉素（RAPA）可以抑制脂肪浸润。但是，全身给予RAPA可能会引起感染、恶心等并发症，而局部给予RAPA可能会导致肌腱细胞的细胞毒性，影响肩袖的愈合。在这项研究中，生物相容性和临床批准的聚己内酯-聚乙二醇（PCL-PEG）被配制成可注射的纳米颗粒，用于持续释放RAPA。结果表明，RAPA/PCL-PEG纳米颗粒（NPs）可以有效地延长RAPA的释放，并显着降低RAPA引起的肌腱细胞毒性。对肩袖延迟修复大鼠脂肪浸润模型的研究表明，每周关节内注射RAPA/PCL-PEG NPs可以更有效地减少大鼠肩袖的脂肪浸润和肌肉萎缩，并导致比每天关节内注射RAPA更好的机械性能和步态改善。这些结果表明，在肩关节局部注射RAPA/PCL‐PEG NP可能是脂肪浸润RCT患者的潜在临床选择。
As a common cause of shoulder pain, rotator cuff tears (RCTs) are difficult to treat clinically because of their unsatisfactory prognosis due to the fatty infiltration caused by muscle‐derived stem cells (MDSCs). Previous studies have found that rapamycin (RAPA) can inhibit fatty infiltration. However, systemic administration of RAPA may cause complications such as infection and nausea, while local administration of RAPA may lead to the cytotoxicity of tendon cells, affecting the healing of rotator cuffs. In this study, biocompatible and clinically approved polycaprolactone‐polyethylene glycol (PCL‐PEG) is formulated into an injectable nanoparticle for the sustained release of RAPA. The results indicate that the RAPA/PCL‐PEG nanoparticles (NPs) can efficiently prolong the release of RAPA and significantly reduce the cytotoxicity of tendon cells caused by RAPA. The study of the fatty infiltration model in rats with delayed rotator cuff repair shows that weekly intraarticular injection of RAPA/PCL‐PEG NPs can more effectively reduce the fatty infiltration and muscle atrophy of rat rotator cuffs and leads to better mechanical properties and gait improvements than a daily intraarticular injection of RAPA. These findings imply that local injection of RAPA/PCL‐PEG NPs in the shoulder joints can be a potential clinical option for RCTs patients with fatty infiltration.