Department of Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstraße 29, D-69120, Heidelberg, Germany.
Institute for Molecular Systems Engineering and Advanced Materials (IMSEAM), Heidelberg University, Im Neuenheimer Feld 225, D-69120, Heidelberg, Germany.
Adv Healthc Mater. 2023 Apr;12(11):e2202789. doi: 10.1002/adhm.202202789. Epub 2023 Jan 16.
The extracellular matrix (ECM) plays an immense role in the homeostasis of tissues and organs, can function as a barrier for infectious agents, but is also exploited by pathogens during infection. Therefore, the development of well-defined 3D ECM models in the form of microcapsules to elucidate the interactions between ECM components and pathogens in confinement and study disease infectivity is important, albeit challenging. Current limitations are mainly attributed to the lack of biocompatible methods for the production of protein-based microcapsules. Herein, hollow ECM-based microcapsules from laminin-111 or laminin-111/collagen IV are generated to investigate the behavior of organisms within confined 3D extracellular matrices. Microcapsules are created using water-in-oil emulsion droplets stabilized by block copolymer surfactants as templates for the charge-mediated attraction of laminin or laminin-collagen proteins to the droplets' inner periphery, allowing for the formation of modular ECM-based microcapsules with tunable biophysical and biochemical properties and organism encapsulation. The release of E. coli-laden ECM-based protein microcapsules into a physiological environment revealed differences in the dynamic behavior of E. coli depending on the constitution of the surrounding ECM protein matrix. The developed ECM-based protein microcapsules have the potential to be implemented in several biomedical applications, including the design of in vitro infection models.
细胞外基质 (ECM) 在组织和器官的动态平衡中起着巨大的作用，可以作为病原体的屏障，但在感染过程中也被病原体利用。因此，开发明确的 3D ECM 模型（微胶囊形式）以阐明 ECM 成分与病原体在受限环境中的相互作用并研究疾病感染力非常重要，尽管具有挑战性。目前的局限性主要归因于缺乏用于生产基于蛋白质的微胶囊的生物相容性方法。本文使用层粘连蛋白-111 或层粘连蛋白-111/IV 型胶原生成基于 ECM 的中空微胶囊，以研究生物在受限的 3D 细胞外基质中的行为。微胶囊是使用油包水乳液液滴作为模板通过嵌段共聚物表面活性剂稳定的，这些模板通过电荷介导的层粘连蛋白或层粘连蛋白-胶原蛋白对液滴内周缘的吸引力来生成，从而允许形成具有可调生物物理和生化特性和生物封装的模块化 ECM 基微胶囊。将载有大肠杆菌的 ECM 基于蛋白质的微胶囊释放到生理环境中，揭示了大肠杆菌的动态行为的差异，这取决于周围 ECM 蛋白质基质的组成。开发的 ECM 基于蛋白质的微胶囊具有在多种生物医学应用中实施的潜力，包括设计体外感染模型。
