Efficacy of engineered FVIII-producing skeletal muscle enhanced by growth factor-releasing co-axial electrospun fibers
Efficacy of engineered FVIII-producing skeletal muscle enhanced by growth factor-releasing co-axial electrospun fibers
复制标题
DOI：
10.1016/j.biomaterials.2010.10.049
复制
发表时间：
2011-02-01
期刊：
影响因子：
14
通讯作者：
Leong, Kam W.
中科院分区：
文献类型：
--
作者：
Liao, I-Chien;Leong, Kam W.
同轴电纺纤维可以为组织工程应用提供形貌和生物化学线索。在这项研究中，我们证明了持续治疗血友病，通过非病毒，组织工程的方法促进生长因子释放同轴电纺纤维。首先在体外将产生FVIII的骨骼肌管工程化在对齐的电纺纤维上，然后植入血友病小鼠中，所述血友病小鼠具有或不具有核-壳电纺纤维层，所述核-壳电纺纤维层设计用于提供血管生成或淋巴管生成生长因子的持续递送，其用于刺激淋巴或血管系统以增强FVIII从植入部位转运到体循环中。皮下植入血友病小鼠后，该构建体在一个月内与宿主组织无缝整合，并根据电纺纤维释放的生长因子特异性诱导血管或淋巴网络浸润。诱导血管生成的工程化构建体导致血浆FVIII持续升高，并显著缩短凝血时间至少2个月。这项研究表明，生物材料辅助的功能性组织工程可以为血友病等遗传疾病提供蛋白质替代疗法。(C)2010爱思唯尔有限公司保留所有权利。
Co-axial electrospun fibers can offer both topographical and biochemical cues for tissue engineering applications. In this study, we demonstrate the sustained treatment of hemophilia through a non-viral, tissue engineering approach facilitated by growth factor-releasing co-axial electrospun fibers. FVIII-producing skeletal myotubes were first engineered on aligned electrospun fibers in vitro, followed by implantation in hemophilic mice with or without a layer of core-shell electrospun fibers designed to provide sustained delivery of angiogenic or lymphangiogenic growth factors, which serves to stimulate the lymphatic or vascular systems to enhance the FVIII transport from the implant site into systemic circulation. Upon subcutaneous implantation into hemophilic mice, the construct seamlessly integrated with the host tissue within one month, and specifically induced either vascular or lymphatic network infiltration in accordance with the growth factors released from the electrospun fibers. Engineered constructs that induced angiogenesis resulted in sustained elevation of plasma FVIII and significantly reduced blood coagulation time for at least 2-months. Biomaterials-assisted functional tissue engineering was shown in this study to offer protein replacement therapy for a genetic disorder such as hemophilia. (C) 2010 Elsevier Ltd. All rights reserved.