Mainik Philipp, Aponte-Santamaría Camilo, Fladung Magdalena, Curticean Ronald Ernest, Wacker Irene, Hofhaus Götz, Bastmeyer Martin, Schröder Rasmus R, Gräter Frauke, Blasco Eva
Institute for Molecular Systems Engineering and Advanced Materials (IMSEAM), Heidelberg University, 69120, Heidelberg, Germany.
Organic Chemistry Institute (OCI), Heidelberg University, 69120, Heidelberg, Germany.
Small. 2025 Jan;21(3):e2408597. doi: 10.1002/smll.202408597. Epub 2024 Nov 27.
Mimicking extracellular matrices holds great potential for tissue engineering in biological and biomedical applications. A key compound for the mechanical stability of these matrices is collagen, which also plays an important role in many intra- and intercellular processes. Two-photon 3D laser printing offers structuring of these matrices with subcellular resolution. So far, efforts on 3D microprinting of collagen have been limited to simple geometries and customized set-ups. Herein, an easily accessible approach is presented using a collagen type I methacrylamide (ColMA) ink system which can be stored at room temperature and be precisely printed using a commercial two-photon 3D laser printer. The formulation and printing parameters are carefully optimized enabling the manufacturing of defined 3D microstructures. Furthermore, these printed microstructures show a fully reversible response upon heating and cooling in multiple cycles, indicating successful collagen folding and unfolding. This experimental observation has been supported by molecular dynamics simulations. Thus, the study opens new perspectives for designing new responsive biomaterials for 4D (micro)printing.
模拟细胞外基质在生物和生物医学应用的组织工程中具有巨大潜力。这些基质机械稳定性的关键化合物是胶原蛋白，它在许多细胞内和细胞间过程中也起着重要作用。双光子3D激光打印能够以亚细胞分辨率构建这些基质。到目前为止，胶原蛋白的3D微打印工作仅限于简单的几何形状和定制设置。在此，我们提出了一种易于实现的方法，使用I型甲基丙烯酰胺胶原蛋白（ColMA）墨水系统，该系统可以在室温下储存，并使用商用双光子3D激光打印机进行精确打印。对配方和打印参数进行了仔细优化，以实现特定3D微结构的制造。此外，这些打印的微结构在多次加热和冷却循环中表现出完全可逆的响应，表明胶原蛋白成功折叠和展开。这一实验观察得到了分子动力学模拟的支持。因此，该研究为设计用于4D（微）打印的新型响应性生物材料开辟了新的前景。
