Romano Nicole H, Sengupta Debanti, Chung Cindy, Heilshorn Sarah C
Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305-4045, USA.
Biochim Biophys Acta. 2011 Mar;1810(3):339-49. doi: 10.1016/j.bbagen.2010.07.005. Epub 2010 Jul 18.
Traditional materials used as in vitro cell culture substrates are rigid and flat surfaces that lack the exquisite nano- and micro-scale features of the in vivo extracellular environment. While these surfaces can be coated with harvested extracellular matrix (ECM) proteins to partially recapitulate the bio-instructive nature of the ECM, these harvested proteins often exhibit large batch-to-batch variability and can be difficult to customize for specific biological studies. In contrast, recombinant protein technology can be utilized to synthesize families of 3 dimensional protein-engineered biomaterials that are cyto-compatible, reproducible, and fully customizable.
Here we describe a modular design strategy to synthesize protein-engineered biomaterials that fuse together multiple repeats of nanoscale peptide design motifs into full-length engineered ECM mimics.
Due to the molecular-level precision of recombinant protein synthesis, these biomaterials can be tailored to include a variety of bio-instructional ligands at specified densities, to exhibit mechanical properties that match those of native tissue, and to include proteolytic target sites that enable cell-triggered scaffold remodeling. Furthermore, these biomaterials can be processed into forms that are injectable for minimally-invasive delivery or spatially patterned to enable the release of multiple drugs with distinct release kinetics.
Given the reproducibility and flexibility of these protein-engineered biomaterials, they are ideal substrates for reductionist biological studies of cell-matrix interactions, for in vitro models of physiological processes, and for bio-instructive scaffolds in regenerative medicine therapies. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine.
用作体外细胞培养底物的传统材料是刚性且平坦的表面,缺乏体内细胞外环境所具有的精细纳米和微米级特征。虽然这些表面可以涂覆收获的细胞外基质(ECM)蛋白以部分重现ECM的生物指导性质,但这些收获的蛋白往往表现出较大的批次间差异,并且难以针对特定生物学研究进行定制。相比之下,可以利用重组蛋白技术合成一系列三维蛋白工程生物材料,这些材料具有细胞相容性、可重复性且完全可定制。
在这里,我们描述了一种模块化设计策略,用于合成蛋白工程生物材料,该材料将多个纳米级肽设计基序的重复序列融合成全长工程化ECM模拟物。
由于重组蛋白合成的分子水平精度,这些生物材料可以进行定制,以特定密度包含多种生物指导配体,展现出与天然组织相匹配的机械性能,并包含蛋白水解靶点,从而实现细胞触发的支架重塑。此外,这些生物材料可以加工成可注射形式用于微创递送,或进行空间图案化以实现具有不同释放动力学的多种药物的释放。
鉴于这些蛋白工程生物材料的可重复性和灵活性,它们是用于细胞-基质相互作用的简化生物学研究、生理过程的体外模型以及再生医学治疗中的生物指导支架的理想底物。本文是名为“纳米技术——在生物医学中的新兴应用”的特刊的一部分。