Kühn Sebastian, Magno Valentina, Zimmermann Ralf, Limasale Yanuar Dwi Putra, Atallah Passant, Stoppa Aukha, Männel Max J, Thiele Julian, Friedrichs Jens, Freudenberg Uwe, Werner Carsten
Institute of Biofunctional Polymer Materials/Max Bergmann Center of Biomaterials Dresden, Leibniz Institute of Polymer Research Dresden, Hohe Str. 6, 01069, Dresden, Germany.
Institute of Physical Chemistry and Polymer Physics, Leibniz Institute of Polymer Research Dresden, Hohe Str. 6, 01069, Dresden, Germany.
Adv Mater. 2025 Jan;37(3):e2409731. doi: 10.1002/adma.202409731. Epub 2024 Oct 24.
Concentration gradients of soluble signaling molecules-morphogens-determine the cellular organization in tissue development. Morphogen-releasing microgels have shown potential to recapitulate this principle in engineered tissue constructs, however, with limited control over the molecular cues in space and time. Inspired by the functionality of sulfated glycosaminoglycans (sGAGs) in morphogen signaling in vivo, a library of sGAG-based microgels is developed and designated as µGel Units to Instruct Development (µGUIDEs). Adjustment of the microgel's sGAG sulfation patterns and concentration enabled the programming of electrostatic affinities that control the release of morphogens. Based on computational analyses of molecular transport processes, µGUIDEs provided unprecedented precision in the spatiotemporal modulation of vascular endothelial growth factor (VEGF) gradients in a microgel-in-gel vasculogenesis model and kidney organoid cultures. The versatile approach offers new options for creating morphogen signaling centers to advance the understanding of tissue and organ development.
可溶性信号分子——形态发生素的浓度梯度决定了组织发育中的细胞组织。释放形态发生素的微凝胶已显示出在工程组织构建物中重现这一原理的潜力，然而，对分子信号在空间和时间上的控制有限。受体内硫酸化糖胺聚糖（sGAGs）在形态发生素信号传导中功能的启发，开发了一个基于sGAG的微凝胶库，并将其命名为指导发育的微凝胶单元（µGUIDEs）。对微凝胶的sGAG硫酸化模式和浓度进行调整，能够对控制形态发生素释放的静电亲和力进行编程。基于分子运输过程的计算分析，µGUIDEs在凝胶内血管生成模型和肾类器官培养中，为血管内皮生长因子（VEGF）梯度的时空调制提供了前所未有的精度。这种通用方法为创建形态发生素信号中心提供了新的选择，以促进对组织和器官发育的理解。
