Three-dimensional cell and organoid cultures rely on the mechanical support of viscoelastic matrices. However, commonly used matrix materials lack control over key cell-instructive properties. Here we report on fully synthetic hydrogels based on DNA libraries that self-assemble with ultrahigh-molecular-weight polymers, forming a dynamic DNA-crosslinked matrix (DyNAtrix). DyNAtrix enables computationally predictable and systematic control over its viscoelasticity, thermodynamic and kinetic parameters by changing DNA sequence information. Adjustable heat activation allows homogeneous embedding of mammalian cells. Intriguingly, stress-relaxation times can be tuned over four orders of magnitude, recapitulating mechanical characteristics of living tissues. DyNAtrix is self-healing, printable, exhibits high stability, cyto- and haemocompatibility, and controllable degradation. DyNAtrix-based cultures of human mesenchymal stromal cells, pluripotent stem cells, canine kidney cysts and human trophoblast organoids show high viability, proliferation and morphogenesis. DyNAtrix thus represents a programmable and versatile precision matrix for advanced approaches to biomechanics, biophysics and tissue engineering.
中文翻译：
三维细胞和类器官培养依赖于粘弹性基质的机械支撑。然而，常用的基质材料缺乏对关键细胞指导特性的控制。在此，我们报告了基于 DNA 文库的全合成水凝胶，该水凝胶与超高分子量聚合物自组装，形成动态 DNA 交联基质 (DyNAtrix)。DyNAtrix 通过改变 DNA 序列信息，能够对其粘弹性、热力学和动力学参数进行计算可预测和系统控制。可调节的热激活允许哺乳动物细胞均匀包埋。有趣的是，应力松弛时间可以调整四个数量级，概括活体组织的机械特性。DyNAtrix 具有自我修复、可打印的特点，具有高稳定性、细胞和血液相容性，和可控降解。基于 DyNAtrix 的人间充质基质细胞、多能干细胞、犬肾囊肿和人滋养层类器官培养物显示出高活力、增殖和形态发生。因此，DyNAtrix 代表了一种可编程且多功能的精密矩阵，适用于生物力学、生物物理学和组织工程的先进方法。
