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Injectable tissue integrating networks from recombinant polypeptides with tunable order
Nature Materials ( IF 37.2 ) Pub Date : 2018-10-15 , DOI: 10.1038/s41563-018-0182-6
Stefan Roberts , Tyler S. Harmon , Jeffrey L. Schaal , Vincent Miao , Kan Li , Andrew Hunt , Yi Wen , Terrence G. Oas , Joel H. Collier , Rohit V. Pappu , Ashutosh Chilkoti

Emergent properties of natural biomaterials result from the collective effects of nanoscale interactions among ordered and disordered domains. Here, using recombinant sequence design, we have created a set of partially ordered polypeptides to study emergent hierarchical structures by precisely encoding nanoscale order–disorder interactions. These materials, which combine the stimuli-responsiveness of disordered elastin-like polypeptides and the structural stability of polyalanine helices, are thermally responsive with tunable thermal hysteresis and the ability to reversibly form porous, viscoelastic networks above threshold temperatures. Through coarse-grain simulations, we show that hysteresis arises from physical crosslinking due to mesoscale phase separation of ordered and disordered domains. On injection of partially ordered polypeptides designed to transition at body temperature, they form stable, porous scaffolds that rapidly integrate into surrounding tissue with minimal inflammation and a high degree of vascularization. Sequence-level modulation of structural order and disorder is an untapped principle for the design of functional protein-based biomaterials.



中文翻译:

具有可调顺序的重组多肽的可注射组织整合网络

天然生物材料的新兴特性是由于有序域和无序域之间的纳米级相互作用的共同作用而产生的。在这里,使用重组序列设计,我们创建了一组部分有序的多肽,以通过精确编码纳米级有序-无序相互作用来研究新兴的层次结构。这些材料结合了无序的弹性蛋白样多肽的刺激响应能力和聚丙氨酸螺旋的结构稳定性,对热响应具有可调的热滞,并具有在阈值温度以上可逆地形成多孔粘弹性网络的能力。通过粗粒度模拟,我们表明,由于有序域和无序域的中尺度相分离,物理交联引起了磁滞现象。注射设计为在体温下转变的部分有序多肽后,它们会形成稳定,多孔的支架,这些支架可以迅速整合到周围组织中,而炎症反应极少,血管形成程度很高。结构顺序和无序的序列水平调节是功能性基于蛋白质的生物材料设计的未开发原理。

更新日期:2018-12-10
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