Stress Relaxation and Composition of Hydrazone-Crosslinked Hybrid Biopolymer-Synthetic Hydrogels Determine Spreading and Secretory Properties of MSCs.
Stress Relaxation and Composition of Hydrazone-Crosslinked Hybrid Biopolymer-Synthetic Hydrogels Determine Spreading and Secretory Properties of MSCs.
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腙交联杂化生物聚合物 - 合成水凝胶的应力松弛及组成决定间充质干细胞的铺展和分泌特性。
DOI：
10.1002/adhm.202200393
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发表时间：
2022-07
影响因子：
10
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
Borelli, Alexandra N.;Young, Mark W.;Kirkpatrick, Bruce E.;Jaeschke, Matthew W.;Mellett, Sarah;Porter, Seth;Blatchley, Michael R.;Rao, Varsha V.;Sridhar, Balaji V.;Anseth, Kristi S.
细胞外基质在机械感知中起着关键作用，从而影响骨髓间充质干/基质细胞（MSCs）的分泌特性。因此，人们对开发具有可调特性的生物材料的兴趣越来越大，用于细胞疗法中MSC的扩增和递送。在本文中，应力松弛水凝胶被合成为含有生物聚合物和合成大分子单体组分的混合网络。用醛或酰肼基团官能化海波酸以形成共价适应性腙网络，其通过用双环壬炔官能化的聚（乙二醇）和含有叠氮化物和苯甲醛部分的异双官能小分子交联剂稳定。调整这些凝胶的组成允许应力松弛的特征时间尺度和应力松弛量的受控变化。在该组成空间上，观察到MSC以更高程度的适应性在制剂中扩散，纵横比为1.60 ± 0.18，雅普核：细胞质比为6.5 ± 1.3。最后，高度应力松弛凝胶中MSC细胞周围蛋白质的最大厚度为1.45 ± 0.38 μm，而非适应性对照中为1.05 ± 0.25 μm。总的来说，这项研究有助于对组成定义的应力松弛对MSC机械感应和分泌的作用有新的认识。在这项工作中，调整应力松弛水凝胶，以研究应力松弛时间尺度的受控变化对间充质干细胞/基质细胞（MSC）的影响。具体而言，一个混合网络，包含生物聚合物和合成的大分子单体成分合成，以检查MSC的机械感应和分泌性能作为应力松弛的函数。比例尺= 50 μm。
The extracellular matrix plays a critical role in mechanosensing and thereby influences the secretory properties of bone-marrow-derived mesenchymal stem/stromal cells (MSCs). As a result, interest has grown in the development of biomaterials with tunable properties for the expansion and delivery of MSCs that are used in cell-based therapies. Herein, stress-relaxing hydrogels are synthesized as hybrid networks containing both biopolymer and synthetic macromer components. Hyaluronic acid is functionalized with either aldehyde or hydrazide groups to form covalent adaptable hydrazone networks, which are stabilized by poly(ethylene glycol) functionalized with bicyclononyne and heterobifunctional small molecule crosslinkers containing azide and benzaldehyde moieties. Tuning the composition of these gels allows for controlled variation in the characteristic timescale for stress relaxation and the amount of stress relaxed. Over this compositional space, MSCs are observed to spread in formulations with higher degrees of adaptability, with aspect ratios of 1.60 ± 0.18, and YAP nuclear:cytoplasm ratios of 6.5 ± 1.3. Finally, a maximum MSC pericellular protein thickness of 1.45 ± 0.38 μm occurred in highly stress-relaxing gels, compared to 1.05 ± 0.25 μm in non-adaptable controls. Collectively, this study contributes a new understanding of the role of compositionally defined stress relaxation on MSCs mechanosensing and secretion. In this work, a stress-relaxing hydrogel was tuned to investigate the impact of controlled variations in stress relaxation timescales on mesenchymal stem/stromal cells (MSCs). Specifically, a hybrid network, containing both biopolymer and synthetic macromer components were synthesized to examine MSCs mechanosensing and secretory properties as a function of stress relaxation. Scale Bar = 50 μm.
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DOI：
10.1002/adma.201303680
发表时间：
2014-02-12
期刊：
Advanced materials (Deerfield Beach, Fla.)
影响因子：
--
作者：
McKinnon DD;Domaille DW;Cha JN;Anseth KS
通讯作者：
Anseth KS
影响因子：
23.9
作者：
Caplan AI;Correa D
通讯作者：
Correa D
影响因子：
16.6
作者：
Chaudhuri O;Gu L;Darnell M;Klumpers D;Bencherif SA;Weaver JC;Huebsch N;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
2
作者：
Lin CS;Xin ZC;Dai J;Lue TF
通讯作者：
Lue TF