Department of Cranio Maxillofacial Surgery, Oral Biotechnology & Bioengineering, University Hospital Zurich and Center of Dental Medicine, University of Zurich Frauenklinikstrasse 24, Nord2 B-843, 8091 Zurich, Switzerland.
Integr Biol (Camb). 2011 Nov;3(11):1102-11. doi: 10.1039/c1ib00045d. Epub 2011 Oct 10.
Engineered artificial microenvironments hold enormous potential as models to study developmental, physiological, pathological, and regenerative processes under highly defined conditions. Such platforms aim at bridging the gap between traditional in vitro 2D culture systems and animal models. By dissecting the biological complexity into an amenable number of parameters, systemic manipulation and study in controllable environments closely resembling the in vivo situation is possible. Novel strategies that address the evaluation of either ECM components, growth factors or cell-cell interactions on cellular behaviour are being developed. However, reliable methods that simultaneously recapitulate the natural instructive microenvironments in terms of cell and matrix composition, biological cues, heterogeneity and geometry are not yet available. Such spatially-defined microenvironments may be necessary to initiate and guide the formation of artificial tissues by morphogenetic processes. In this work, we introduce a flexible strategy that relies on the combination of artificial extracellular matrices with patterning techniques as well as a layer-by-layer approach to mimic rationally-designed instructive milieus. By a rational arrangement of cells and defined biochemical and biophysical extracellular cues, we report control of cell migration and generation of an artificial vascularized bone tissue-like construct.
工程化人工微环境具有巨大的潜力，可以在高度定义的条件下作为模型来研究发育、生理、病理和再生过程。这些平台旨在弥合传统的体外 2D 培养系统和动物模型之间的差距。通过将生物学复杂性分解为可处理的参数数量，可以在类似于体内的可控环境中进行系统的操作和研究。目前正在开发新的策略，以评估细胞外基质成分、生长因子或细胞-细胞相互作用对细胞行为的影响。然而，目前还没有可靠的方法可以同时再现细胞和基质组成、生物线索、异质性和几何形状等方面的自然指导微环境。这样的空间限定的微环境可能对于通过形态发生过程启动和指导人工组织的形成是必要的。在这项工作中，我们引入了一种灵活的策略，该策略依赖于人工细胞外基质与图案形成技术的结合，以及层-层方法来模拟合理设计的指导环境。通过细胞的合理排列以及定义明确的生化和生物物理细胞外线索，我们报告了对细胞迁移的控制，并生成了人工血管化骨组织样结构。
