Department of Materials Science & Engineering, Stanford University, Stanford, CA, 94305, USA.
Department of Biomedical Engineering, University of California, Davis 451 Health Sciences Dr, GBSF 3315, Davis, CA, 95616, USA.
Adv Mater. 2024 Nov;36(45):e2407794. doi: 10.1002/adma.202407794. Epub 2024 Sep 5.
The biochemical and biophysical properties of the extracellular matrix (ECM) play a pivotal role in regulating cellular behaviors such as proliferation, migration, and differentiation. Engineered protein-based hydrogels, with highly tunable multifunctional properties, have the potential to replicate key features of the native ECM. Formed by self-assembly or crosslinking, engineered protein-based hydrogels can induce a range of cell behaviors through bioactive and functional domains incorporated into the polymer backbone. Using recombinant techniques, the amino acid sequence of the protein backbone can be designed with precise control over the chain-length, folded structure, and cell-interaction sites. In this review, the modular design of engineered protein-based hydrogels from both a molecular- and network-level perspective are discussed, and summarize recent progress and case studies to highlight the diverse strategies used to construct biomimetic scaffolds. This review focuses on amino acid sequences that form structural blocks, bioactive blocks, and stimuli-responsive blocks designed into the protein backbone for highly precise and tunable control of scaffold properties. Both physical and chemical methods to stabilize dynamic protein networks with defined structure and bioactivity for cell culture applications are discussed. Finally, a discussion of future directions of engineered protein-based hydrogels as biomimetic cellular scaffolds is concluded.
细胞外基质（ECM）的生化和生物物理特性在调节细胞行为方面起着关键作用，如增殖、迁移和分化。具有高度可调多功能特性的工程蛋白水凝胶有可能复制天然 ECM 的关键特征。通过自组装或交联形成的工程蛋白水凝胶可以通过整合到聚合物主链中的生物活性和功能结构域来诱导一系列细胞行为。通过重组技术，可以精确控制蛋白质主链的氨基酸序列，控制链长、折叠结构和细胞相互作用位点。在这篇综述中，从分子和网络水平讨论了工程蛋白水凝胶的模块化设计，并总结了最近的进展和案例研究，以突出用于构建仿生支架的各种策略。本文重点介绍了用于构建蛋白质主链的结构块、生物活性块和刺激响应块的氨基酸序列，用于对支架性能进行高度精确和可调的控制。讨论了用于细胞培养应用的具有定义结构和生物活性的动态蛋白质网络的物理和化学稳定方法。最后，讨论了作为仿生细胞支架的工程蛋白水凝胶的未来发展方向。
