Department of Materials Science & Engineering , Stanford University , Stanford , California 94305 , United States.
Department of Biology and Biological Engineering , Chalmers University of Technology , Gothenburg SE-412 96 , Sweden.
ACS Appl Mater Interfaces. 2018 Jul 5;10(26):21808-21815. doi: 10.1021/acsami.8b02461. Epub 2018 Jun 20.
The fabrication of three dimensional "bead-string" microstructured hydrogels is rationally achieved by controlling the relative timing of chemical crosslinking and physical self-assembly processes of an engineered protein. To demonstrate this strategy, an elastin-like protein (ELP) amino acid sequence was selected to enable site-specific chemical crosslinking and thermoresponsive physical self-assembly. This method allows the tuning of material microstructures without altering the ELP amino acid sequence but simply through controlling the chemical crosslinking extent before the thermally induced, physical coacervation of ELP. A loosely crosslinked network enables ELP to have greater chain mobility, resulting in phase segregation into larger beads. By contrast, a network with higher crosslinking density has restricted ELP chain mobility, resulting in more localized self-assembly into smaller beads. As a proof of concept application for this facile assembly process, we demonstrate one-pot, simultaneous, dual encapsulation of hydrophilic and hydrophobic model drugs within the microstructured hydrogel and differential release rates of the two drugs from the material.
通过控制工程化蛋白质的化学交联和物理自组装过程的相对时间，合理地制造出三维“串珠”微结构水凝胶。为了证明这一策略，选择了弹性蛋白样蛋白（ELP）氨基酸序列，以实现位点特异性化学交联和热响应物理自组装。这种方法允许在不改变 ELP 氨基酸序列的情况下调整材料的微观结构，而只需通过控制热诱导 ELP 物理凝聚之前的化学交联程度即可。交联程度较低的网络使 ELP 具有更大的链迁移率，从而导致相分离成较大的珠子。相比之下，具有更高交联密度的网络限制了 ELP 链的迁移率，导致更局部的自组装成较小的珠子。作为这种简便组装过程的概念验证应用，我们展示了在微结构水凝胶中同时封装亲水性和疏水性模型药物的一锅法，以及从材料中两种药物的不同释放速率。
