In situ regeneration of bioactive coatings enabled by an evolved Staphylococcus aureus sortase A.
In situ regeneration of bioactive coatings enabled by an evolved Staphylococcus aureus sortase A.
复制标题
DOI：
10.1038/ncomms11140
复制
发表时间：
2016-04-13
影响因子：
16.6
通讯作者：
Chaikof EL
中科院分区：
文献类型：
--
作者：
Ham HO;Qu Z;Haller CA;Dorr BM;Dai E;Kim W;Liu DR;Chaikof EL
生物活性分子的表面固定是设计具有改进的临床性能能力的可植入装置和生物传感器的中心范例。然而，表面成分的体内降解或变性通常限制生物活性膜的长期性能。在这里，我们证明了通过两步剥离和充电循环重复再生共价固定的生物活性分子的单分子薄膜的能力。通过实验室进化的金黄色葡萄球菌分选酶A（eSrtA）的可逆转肽作用使得能够在全血存在下快速固定抗血栓形成膜，并允许在体外进行多个循环的膜再生，从而保留其生物活性。此外，eSrtA转肽促进了医疗器械在体内植入后通过去除和修复膜成分原位表面再造。这些研究建立了一个快速，正交和可逆的生化方案，再生选择性的分子成分，有可能延长生物活性膜的寿命。 生物活性涂层提供了一种调节宿主对植入物反应的策略，但其在体内的快速降解阻碍了其向临床的转化。在这里，作者使用一种工程细菌蛋白在体外和装置植入后原位再生抗血栓形成膜。
Surface immobilization of bioactive molecules is a central paradigm in the design of implantable devices and biosensors with improved clinical performance capabilities. However, in vivo degradation or denaturation of surface constituents often limits the long-term performance of bioactive films. Here we demonstrate the capacity to repeatedly regenerate a covalently immobilized monomolecular thin film of bioactive molecules through a two-step stripping and recharging cycle. Reversible transpeptidation by a laboratory evolved Staphylococcus aureus sortase A (eSrtA) enabled the rapid immobilization of an anti-thrombogenic film in the presence of whole blood and permitted multiple cycles of film regeneration in vitro that preserved its biological activity. Moreover, eSrtA transpeptidation facilitated surface re-engineering of medical devices in situ after in vivo implantation through removal and restoration film constituents. These studies establish a rapid, orthogonal and reversible biochemical scheme to regenerate selective molecular constituents with the potential to extend the lifetime of bioactive films. Bioactive coatings offer a strategy to modulate host response to implants, but their translation to the clinic is hampered by their fast in vivo degradation. Here, the authors use an engineered bacterial protein to regenerate an anti-thrombogenic film in vitro and in situ after device implantation.