Unidirectional gene delivery electrospun fibrous membrane via charge repulsion for tendon repair  

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作  者:Jingwen Liu Liang Chen Zhenyu Sun Zaijin Tao Volotovski Pavel Yusheng Li Fei Wang Wenguo Cui Shen Liu 

机构地区:[1]Department of Orthopaedics,Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration,Shanghai 200233,PR China [2]Department of Orthopaedics,Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases,Shanghai Institute of Traumatology and Orthopaedics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,197 Ruijin 2nd Road,Shanghai 200025,PR China [3]Republican Scientific and Practical Center of Traumatology and Orthopedics,Belarusian State Medical University,Minsk 220024,Belarus [4]Department of Orthopedics,Xiangya Hospital,Central South University,Changsha 410008,Hunan,PR China

出  处:《Bioactive Materials》2024年第7期191-205,共15页生物活性材料(英文)

基  金:supported by the National Natural Science Foundation of China (No.82172408 and 81902234);Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program (No.20191829);Program of Shanghai Academic/Technology Research Leader (22XD1422600);Shanghai Municipal Health Commission (Grant No.2022YQ073).

摘  要:Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases.However,unidirectional targeting gene therapy is always desired at the tissue interface.In this study,inspired by the principle that like charges repulse each other,a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers,thus realizing unidirectional gene therapy at the tendon-paratenon interface.Under the charge repulsion of positively charged layer,more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue,which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation,but also avoided adverse effects on the fragile endogenous healing of tendon itself.In summary,this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.

关 键 词:Unidirectional delivery Charge repulsion Gene therapy Tendon repair 

分 类 号:R318[医药卫生—生物医学工程]

 

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