Transient Competitors to Modulate Dynamic Covalent Cross-Linking of Recombinant Hydrogels
Transient Competitors to Modulate Dynamic Covalent Cross-Linking of Recombinant Hydrogels
复制标题
调节重组水凝胶动态共价交联的瞬时竞争剂
DOI：
10.1021/acs.chemmater.3c01575
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发表时间：
2023
影响因子：
8.6
通讯作者：
Heilshorn, Sarah C.
中科院分区：
文献类型：
--
作者：
Gilchrist, Aidan E.;Liu, Yueming;Klett, Katarina;Liu, Yu-Chung;Ceva, Sofía;Heilshorn, Sarah C.
通过动态共价化学（DCC）交联的水凝胶具有刚性和可重塑性，使其成为组织工程应用的理想仿生材料。由于DCC交联的可逆性，有机会通过使用小分子竞争者来暂时控制水凝胶网络的形成。具体来说，我们加入了低分子量的竞争者，当它们通过重组水凝胶扩散时，可逆地破坏腙交联的形成。利用互补的实验、计算和理论聚合物物理方法，我们提出了一系列可预测地改变水凝胶凝胶化时间和力学的竞争对手。通过改变竞争对手的化学性质，我们将关键反应参数（正反反应速率和热力学平衡常数）与渗透网络的延迟开始、水凝胶凝胶化时间的增加和水凝胶刚度的瞬时控制联系起来。使用人类肠道类器官作为模型系统，我们展示了调整重组水凝胶凝胶动力学的能力，以均匀地封装个体，患者来源的干细胞并将其增殖成三维结构。综上所述，我们的数据建立了一个有效的框架，将瞬态竞争对手的分子水平参数与预测的大分子网络特性联系起来。随着人们对仿生、dcc交联水凝胶的兴趣不断增长，这些结果将使组织工程定制动态生物材料的基本原理设计成为可能。
Hydrogels cross-linked by dynamic covalent chemistry (DCC) are stiff and remodelable, making them ideal biomimetics for tissue engineering applications. Due to the reversibility of DCC cross-links, the opportunity exists to transiently control hydrogel network formation through the use of small molecule competitors. Specifically, we incorporate low molecular weight competitors that reversibly disrupt the formation of hydrazone cross-links as they diffuse through a recombinant hydrogel. Using complementary experimental, computational, and theoretical polymer physics approaches, we present a family of competitors that predictably alter hydrogel gelation time and mechanics. By changing the competitor chemistry, we connect key reaction parameters (forward and reverse reactions rates and thermodynamic equilibrium constants) to the delayed onset of a percolated network, increased hydrogel gelation time, and transient control of hydrogel stiffness. Using human intestinal organoids as a model system, we demonstrate the ability to tune gelation kinetics of a recombinant hydrogel for uniform encapsulation of individual, patient-derived stem cells and their proliferation into three-dimensional structures. Taken together, our data establish a validated framework to relate molecular-level parameters of transient competitors to predicted macromolecular-network properties. As interest in biomimetic, DCC-cross-linked hydrogels continues to grow, these results will enable the rationale design of bespoke, dynamic biomaterials for tissue engineering.
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影响因子：
7.4
作者：
Fritz, Kristofer S.;Petersen, Dennis. R.
通讯作者：
Petersen, Dennis. R.
影响因子：
9.7
作者：
Gilchrist AE;Serrano JF;Ngo MT;Hrnjak Z;Kim S;Harley BAC
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15
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影响因子：
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通讯作者：
Kellomaki, Minna
影响因子：
29.4
作者：
Sato, Toshiro;Stange, Daniel E.;Clevers, Hans
通讯作者：
Clevers, Hans