粘附
聚乳酸
药品
组织粘连
膜
细胞生物学
药理学
化学
生物医学工程
聚合物
医学
生物化学
生物
有机化学
作者
Yanhao Li,Chengfang Hu,Bo Hu,Jian Tian,Gang Zhao,Chuandong Cai,Yuange Li,Zhenyu Sun,Shuo Wang,Sa Pang,Rong Bao,Zaijing Tao,Huajiang Chen,Jinglei Wu,Shen Liu
标识
DOI:10.1002/adhm.202203078
摘要
The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGFβ) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGFβ/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA.
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