Biomimicking Dual-Responsive Extracellular Matrix Restoring Extracellular Balance through the Na/K-ATPase Pathway
Biomimicking Dual-Responsive Extracellular Matrix Restoring Extracellular Balance through the Na/K-ATPase Pathway
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仿生双响应细胞外基质通过 Na/K-ATP 酶途径恢复细胞外平衡
DOI：
10.1021/acsami.9b05420
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发表时间：
2019
影响因子：
9.5
通讯作者：
Yin Jinghua
中科院分区：
文献类型：
--
作者：
Luan Xingkun;Wang Haozheng;Xiang Zehong;Ma Zhifang;Zhao Jiruo;Feng Ying;Shi Qiang;Yin Jinghua
模拟生理细胞外基质（ECM）的生物医学植入物是一种调节细胞微环境以改善植入物完整性和寿命的新策略。然而，仿生ECM对病理变化的敏感性低，并且在体内恢复生理状态的效率低。为了克服这些问题，活性氧物质（ROS）和K+双响应微/纳米纤维，封装抗坏血酸-2-葡萄糖苷（AA-2G）的弹性体基板上制造静电纺丝模拟ECM。该策略基于这样的事实：活性氧和K+的双重反应增强了细胞外基质对病理变化的敏感性，并且AA-2G从细胞外基质递送到细胞膜促进了Na/K-ATP酶的重新激活并使细胞病变状态转变为正常状态。我们证明，活性氧和钾离子响应的三聚体的聚（乙二醇）二丙烯酸酯、1，2-乙二硫醇和4-硝基苯并-18-冠-6-醚成功合成了PEGDA-EDT-BCAm复合物，通过反应静电纺丝制备（己内酯）/PEGDA-EDT-BCAm/AA-2G微/纳米纤维; ECM对细胞内ROS和K+浓度敏感，释放AA-2G，AA-2G靶向细胞膜，清除过量的ROS，激活Na/K-ATP酶;结果，ECM在体外和体内均降低氧化应激并恢复细胞外生理状态。这项工作提供了设计植入物的基本原则，该植入物可以调节细胞外微环境，同时避免致病性，以提高植入物的完整性和体内寿命。
Biomedical implant mimicking the physiological extracellular matrix (ECM) is a new strategy to modulate the cell microenvironment to improve implant integrity and longevity. However, the biomimicking ECM suffers from low sensitivity to pathological change and low efficiency to restore the physiological state in vivo. To overcome these problems, reactive oxygen species (ROS) and K+dual-responsive micro-/nanofibers that encapsulate ascorbic acid-2-glucoside (AA-2G) are fabricated on an elastomer substrate with electrospinning to mimic the ECM. The strategy is based on the fact that ROS and K+dual responsiveness enhance the sensitivity of the ECM to pathological changes and delivery of AA-2G from the ECM to cell membrane promotes reactivating Na/K-ATPase and shifting cellular diseased conditions to the normal state. We demonstrate that the ROS and K+-responsive tripolymer of poly(ethylene glycol)diacrylate, 1,2-ethanedithiol, and 4-nitrobenzo-18-crown-6-ether (PEGDA–EDT–BCAm) are synthesized successfully; the ECM composed of acylated poly(caprolactone)/PEGDA–EDT–BCAm/AA-2G micro-/nanofibers is prepared through reactive electrospinning; the ECM is sensitive to ROS and K+concentration in the microenvironment to release AA-2G, which targets the membrane to remove the excessive ROS and reactivate Na/K-ATPase; as a result, the ECM reduces oxidative stress and restores the extracellular physiological state both in vitro and in vivo. This work provides basic principles to design an implant that can adjust the extracellular microenvironment while avoiding pathogenicity to improve implant integrity and longevity in vivo.