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利用集成建模和基因工程丝弹性蛋白样蛋白设计多刺激响应水凝胶

Design of Multistimuli Responsive Hydrogels Using Integrated Modeling and Genetically Engineered Silk-Elastin-Like Proteins.

作者信息

Huang Wenwen, Tarakanova Anna, Dinjaski Nina, Wang Qin, Xia Xiaoxia, Chen Ying, Wong Joyce Y, Buehler Markus J, Kaplan David L

机构信息

Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.

Laboratory for Atomistic and Molecular Mechanics (LAMM), Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

出版信息

Adv Funct Mater. 2016 Jun 20;26(23):4113-4123. doi: 10.1002/adfm.201600236. Epub 2016 Apr 15.

Abstract

Elastomeric, robust, and biocompatible hydrogels are rare, while the need for these types of biomaterials in biomedical-related uses remains high. Here, a new family of genetically engineered silk-elastin copolymers (SELPs) with encoded enzymatic crosslinking sites is developed for a new generation of stimuli-responsive yet robust hydrogels. Input into the designs is guided by simulation, and realized via genetic engineering strategies. The avoidance of gamma irradiation or chemical crosslinking during gel fabrication, in lieu of an enzymatic process, expands the versatility of these new gels for the incorporation of labile proteins and cells. In the present study, the new SELP hydrogels offers sequence dependent, reversible stimuli-responsive features. Their stiffness covers almost the full range of the elasticity of soft tissues. Further, physical modification of the silk domains provided a secondary control point to fine-tune mechanical stiffness while preserving stimuli-responsive features, with implications for a variety of biomedical materials and device needs.

摘要

具有弹性、坚固且生物相容的水凝胶十分罕见,而生物医学相关用途对这类生物材料的需求仍然很高。在此,我们开发了一个新的基因工程丝-弹性蛋白共聚物(SELP)家族,其具有编码的酶交联位点,用于新一代刺激响应性且坚固的水凝胶。设计过程以模拟为指导,并通过基因工程策略实现。在凝胶制备过程中避免使用伽马射线辐照或化学交联,代之以酶促过程,这扩展了这些新型凝胶在掺入不稳定蛋白质和细胞方面的多功能性。在本研究中,新型SELP水凝胶具有序列依赖性、可逆的刺激响应特性。它们的硬度几乎涵盖了软组织弹性的整个范围。此外,对丝域的物理修饰提供了一个二级控制点,可在保留刺激响应特性的同时微调机械硬度,这对各种生物医学材料和设备需求具有重要意义。

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