A great variety of natural and synthetic polymer materials have been utilized in soft tissue engineering as extracellular matrix (ECM) materials. Natural polymers, such as collagen and fibrin hydrogels, have experienced especially broad adoption due to the high density of cell adhesion sites compared to their synthetic counterparts, ready availability, and ease of use. However, these and other hydrogels lack the structural and mechanical anisotropy that define the ECM in many tissues, such as skeletal and cardiac muscle, tendon, and cartilage. Herein, we present a facile, low-cost, and automated method of preparing collagen microfibers, organizing these fibers into precisely controlled mesh designs, and embedding these meshes in a bulk hydrogel, creating a composite biomaterial suitable for a wide variety of tissue engineering and regenerative medicine applications. With the assistance of custom software tools described herein, mesh patterns are designed by a digital graphical user interface and translated into protocols that are executed by a custom mesh collection and organization device. We demonstrate a high degree of precision and reproducibility in both fiber and mesh fabrication, evaluate single fiber mechanical properties, and provide evidence of collagen self-assembly in the microfibers under standard cell culture conditions. This work offers a powerful, flexible platform for the study of tissue engineering and cell material interactions, as well as the development of therapeutic biomaterials in the form of custom collagen microfiber patterns that will be accessible to all through the methods and techniques described here. Impact Statement Collagen microfiber meshes have immediate and broad applications in tissue engineering research and show high potential for later use in clinical therapeutics due to their compositional similarities to native extracellular matrix and tunable structural and mechanical characteristics. Physical and biological characterizations of these meshes demonstrate physiologically relevant mechanical properties, native-like collagen structure, and cytocompatibility. The methods presented herein not only describe a process through which custom collagen microfiber meshes can be fabricated but also provide the reader with detailed device plans and software tools to produce their own bespoke meshes through a precise, consistent, and automated process.

中文翻译：

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定制胶原微纤维支架的数字设计和自动化制造。

多种天然和合成聚合物材料已在软组织工程中用作细胞外基质（ECM）材料。天然聚合物，例如胶原蛋白和纤维蛋白水凝胶，由于与合成聚合物相比具有高密度的细胞粘附位点、易于获得且易于使用，因此得到了特别广泛的采用。然而，这些水凝胶和其他水凝胶缺乏在许多组织中定义 ECM 的结构和机械各向异性，例如骨骼肌和心肌、肌腱和软骨。在此，我们提出了一种简便、低成本和自动化的方法来制备胶原微纤维，将这些纤维组织成精确控制的网格设计，并将这些网格嵌入块状水凝胶中，从而创建适用于各种组织工程和生物材料的复合生物材料。再生医学应用。在本文描述的定制软件工具的帮助下，网格图案由数字图形用户界面设计并转换成由定制网格收集和组织设备执行的协议。我们展示了纤维和网状制造的高精度和可重复性，评估单纤维机械性能，并提供标准细胞培养条件下微纤维中胶原蛋白自组装的证据。这项工作为组织工程和细胞材料相互作用的研究以及以定制胶原微纤维图案形式开发治疗性生物材料提供了一个强大、灵活的平台，所有人都可以通过此处描述的方法和技术获得这种材料。影响陈述胶原微纤维网在组织工程研究中具有直接和广泛的应用，并且由于其与天然细胞外基质的成分相似以及可调节的结构和机械特性，因此在临床治疗中显示出巨大的潜力。这些网状物的物理和生物特征证明了生理相关的机械特性、天然胶原蛋白结构和细胞相容性。本文提出的方法不仅描述了可以制造定制胶原微纤维网的过程，而且还为读者提供了详细的设备计划和软件工具，以通过精确、一致和自动化的过程生产他们自己的定制网。