title: Therapeutic angiogenesis in ischemic muscles after local injection of fragmented fibers with loaded traditional Chinese medicine.
abstract: Therapeutic angiogenesis remains the most effective method to re-establish a proper blood flow in ischemic tissues. There is a great clinical need to identify an injectable format to achieve a well accumulation following local administration and a sustained delivery of biological factors at the ischemic sites. In the current study, fragmented nanofibers with loaded traditional Chinese medicines, astragaloside IV (AT), the main active ingredient of astragalus, and ferulic acid (FA), the main ingredient of angelica, were proposed to promote the microvessel formation after intramuscular injection into ischemic hindlimbs. Fragmented fibers with average lengths of 5 (FF-5), 20 (FF-20) and 80 μm (FF-80) were constructed by the cryocutting of aligned electrospun fibers. Their dispersion in sodium alginate solution (0.2%) indicated good injectability. After injection into the quadriceps muscles of the hindlimbs, FF-20 and FF-80 fiber fragments showed higher tissue retentions than FF-5, and around 90% of the injected doses were determined after 7 days. On a hindlimb ischemia model established by ligating the femoral arteries, intramuscular injection of the mixtures of FA-loaded and AT-loaded FF-20 fiber fragments substantially reduced the muscle degeneration with minimal fibrosis formation, significantly enhanced the neovessel formation and hindlimb perfusion in the ischemic tissues, and efficiently promoted the limb salvage with few limb losses. Along with the easy manipulation and lower invasiveness for in vivo administration, fragmented fibers should become potential drug carriers for disease treatment, wound recovery and tissue repair after local injection.
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. China. xhli@swjtu.edu.cn.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Li
authors.forename: Huiying
authors.initials: H
authors.lastname: Wan
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.forename: Maohua
authors.initials: M
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Luo
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D006614:Hindlimb / Q000098:blood supply / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology; D008516:Medicine, Chinese Traditional; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012503:Saponins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A