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Tackling muscle fibrosis: From molecular mechanisms to next generation engineered models to predict drug delivery
Advanced Drug Delivery Reviews ( IF 16.1 ) Pub Date : 2018-03-05 , DOI: 10.1016/j.addr.2018.02.009
S. Bersini , M. Gilardi , M. Mora , S. Krol , C. Arrigoni , C. Candrian , S. Zanotti , M. Moretti

Muscle fibrosis represents the end stage consequence of different diseases, among which muscular dystrophies, leading to severe impairment of muscle functions. Muscle fibrosis involves the production of several growth factors, cytokines and proteolytic enzymes and is strictly associated to inflammatory processes. Moreover, fibrosis causes profound changes in tissue properties, including increased stiffness and density, lower pH and oxygenation. Up to now, there is no therapeutic approach able to counteract the fibrotic process and treatments directed against muscle pathologies are severely impaired by the harsh conditions of the fibrotic environment. The design of new therapeutics thus need innovative tools mimicking the obstacles posed by the fibrotic environment to their delivery. This review will critically discuss the role of in vivo and 3D in vitro models in this context and the characteristics that an ideal model should possess to help the translation from bench to bedside of new candidate anti-fibrotic agents.



中文翻译:

解决肌肉纤维化:从分子机制到下一代工程模型来预测药物输送

肌肉纤维化代表不同疾病的最终结果,其中包括肌肉营养不良症,导致肌肉功能严重受损。肌肉纤维化涉及多种生长因子,细胞因子和蛋白水解酶的产生,并且与炎症过程密切相关。此外,纤维化会导致组织特性发生深刻变化,包括增加硬度和密度,降低pH值和氧合作用。迄今为止,还没有能够抵消纤维化过程的治疗方法,针对纤维病理的治疗因纤维化环境的恶劣条件而严重受损。因此,新疗法的设计需要创新的工具来模仿纤维化环境对其交付所造成的障碍。

更新日期:2018-03-05
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