Laboratory of Molecular Materials, Division of Biophysics and Bioengineering, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden. Equal contribution.
Biofabrication. 2020 Jul 1;12(3):035031. doi: 10.1088/1758-5090/ab9490.
Hydrogels are used in a wide range of biomedical applications, including three-dimensional (3D) cell culture, cell therapy and bioprinting. To enable processing using advanced additive fabrication techniques and to mimic the dynamic nature of the extracellular matrix (ECM), the properties of the hydrogels must be possible to tailor and change over time with high precision. The design of hydrogels that are both structurally and functionally dynamic, while providing necessary mechanical support is challenging using conventional synthesis techniques. Here, we show a modular and 3D printable hydrogel system that combines a robust but tunable covalent bioorthogonal cross-linking strategy with specific peptide-folding mediated interactions for dynamic modulation of cross-linking and functionalization. The hyaluronan-based hydrogels were covalently cross-linked by strain-promoted alkyne-azide cycloaddition using multi-arm poly(ethylene glycol). In addition, a de novo designed helix-loop-helix peptide was conjugated to the hyaluronan backbone to enable specific peptide-folding modulation of cross-linking density and kinetics, and hydrogel functionality. An array of complementary peptides with different functionalities was developed and used as a toolbox for supramolecular tuning of cell-hydrogel interactions and for controlling enzyme-mediated biomineralization processes. The modular peptide system enabled dynamic modifications of the properties of 3D printed structures, demonstrating a novel route for design of more sophisticated bioinks for four-dimensional bioprinting.
水凝胶在广泛的生物医学应用中得到了应用，包括三维（3D）细胞培养、细胞治疗和生物打印。为了能够使用先进的添加剂制造技术进行处理，并模拟细胞外基质（ECM）的动态特性，必须能够随着时间的推移高精度地调整和改变水凝胶的特性。使用传统的合成技术设计既具有结构又具有功能动态性，同时提供必要的机械支撑的水凝胶具有挑战性。在这里，我们展示了一种模块化和 3D 可打印的水凝胶系统，该系统结合了强大但可调的共价生物正交交联策略以及特定的肽折叠介导的相互作用，用于动态调节交联和功能化。基于透明质酸的水凝胶通过应变促进的炔基-叠氮化物环加成反应用多臂聚（乙二醇）进行共价交联。此外，还将新设计的螺旋-环-螺旋肽偶联到透明质酸主链上，以实现对交联密度和动力学以及水凝胶功能的特定肽折叠调节。开发了一系列具有不同功能的互补肽，并将其用作超分子调节细胞-水凝胶相互作用和控制酶介导的生物矿化过程的工具包。模块化的肽系统能够动态地修改 3D 打印结构的特性，为用于四维生物打印的更复杂生物墨水的设计提供了一种新途径。
