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Modulating Viscoelasticity, Stiffness, and Degradation of Synthetic Cellular Niches via Stoichiometric Tuning of Covalent versus Dynamic Noncovalent Cross-Linking
ACS Central Science ( IF 12.7 ) Pub Date : 2018-07-20 00:00:00 , DOI: 10.1021/acscentsci.8b00170
Yu Tan 1 , Henry Huang 1 , David C. Ayers 1 , Jie Song 1
Affiliation  

Viscoelasticity, stiffness, and degradation of tissue matrices regulate cell behavior, yet predictive synergistic tuning of these properties in synthetic cellular niches remains elusive. We hypothesize that reversible physical cross-linking can be quantitatively introduced to synthetic hydrogels to accelerate stress relaxation and enhance network stiffness, while strategic placement of isolated labile linkages near cross-linking sites can predict hydrogel degradation, both of which are essential for creating adaptive cellular niches. To test these hypotheses, chondrocytes were encapsulated in hydrogels formed by biorthogonal covalent and noncovalent physical cross-linking of a pair of hydrophilic building blocks. The stiffer and more viscoelastic hydrogels with DBCO–DBCO physical cross-links facilitated proliferation and chondrogenic ECM deposition of encapsulated cells by dissipating stress imposed by expanding cell mass/ECM via dynamic disruption/reformation of physical cross-links. Degradation of labile linkages near covalent cross-linkers further facilitated cell proliferation and timed cell release while maintaining chondrogenic phenotype. This work presents new chemical tools for engineering permissive synthetic niches for cell encapsulation, 3D expansion, and release.

中文翻译:

通过共价与动态非共价交联的化学计量比调节合成细胞壁ches的粘弹性,刚度和降解

粘弹性,刚度和组织基质的降解调节细胞行为,但是在合成细胞壁ches中这些特性的预测性协同调节仍然难以捉摸。我们假设可以将可逆的物理交联定量引入合成水凝胶中,以加速应力松弛并增强网络刚度,而将孤立的不稳定键战略性地放置在交联部位附近可以预测水凝胶降解,这对于创建适应性细胞至关重要壁。为了检验这些假设,将软骨细胞封装在由一对亲水结构单元的双正交共价和非共价物理交联形成的水凝胶中。具有DBCO-DBCO物理交联键的更硬,更具粘弹性的水凝胶,通过分散因物理交联键的动态破坏/重组而扩大细胞质量/ ECM所施加的应力,促进了被囊化细胞的增殖和软骨生成ECM沉积。接近共价交联剂的不稳定键的降解进一步促进了细胞增殖和定时释放细胞,同时保持了软骨形成表型。这项工作提出了新的化学工具,用于工程化许可的合成壁ches,用于细胞封装,3D扩展和释放。接近共价交联剂的不稳定键的降解进一步促进了细胞增殖和定时释放细胞,同时保持了软骨形成表型。这项工作提出了新的化学工具,用于工程化许可的合成壁ches,用于细胞封装,3D扩展和释放。接近共价交联剂的不稳定键的降解进一步促进了细胞增殖和定时释放细胞,同时保持了软骨形成表型。这项工作提出了新的化学工具,用于工程化许可的合成壁ches,用于细胞封装,3D扩展和释放。
更新日期:2018-07-20
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