Fiber Density Modulates Cell Spreading in 3D Interstitial Matrix Mimetics
Fiber Density Modulates Cell Spreading in 3D Interstitial Matrix Mimetics
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DOI：
10.1021/acsbiomaterials.9b00141
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发表时间：
2019-06-01
影响因子：
5.8
通讯作者：
Baker, Brendon M.
中科院分区：
文献类型：
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作者：
Matera, Daniel L.;Wang, William Y.;Baker, Brendon M.
细胞表型深受细胞外基质 (ECM) 的影响，细胞外基质是一种复杂的组织特异性三维结构，具有独特的生物物理和生化特性。由于天然来源的细胞培养平台难以可控调节，工程合成 ECM 促进了我们对特定基质特性如何指导细胞行为的理解。然而，合成方法通常缺乏纤维结构，这是体内基质和间质 ECM 的标志。为了构建具有生理微观结构的可调仿生模型，我们开发了一种通用方法来生成 3D 模块化纤维结构。可光交联的聚合物被静电纺丝，光图案化成所需的长度，并与细胞一起封装在天然生物聚合物、半合成和合成水凝胶中。与缺乏这种纤维结构的凝胶相比，封装在纤维增强水凝胶复合材料（FHC）中的细胞表现出加速的铺展率。此外，在恒定体积水凝胶弹性模量下纤维密度的增加产生了形态上不同的细胞群，并在 3D 中调节了细胞机械传感，机械敏感转录因子 Yes 相关蛋白 (YAP) 的核定位增加证明了这一点。这项工作记录了 3D 物理引导线索的影响，并建立了一种新方法来生成更多生理组织和疾病特定的仿生模型。
Cellular phenotype is heavily influenced by the extracellular matrix (ECM), a ECM ekes composites Analysis complex and tissue-specific three-dimensional structure with distinct biophysical and biochemical properties. As naturally derived cell culture platforms are difficult to controllably modulate, engineered synthetic ECMs have facilitated our understanding of how specific matrix properties direct cell behavior. However, synthetic approaches typically lack fibrous topography, a hallmark of stromal and interstitial ECMs in vivo. To construct tunable biomimetic models with physiologic microstructure, we developed a versatile approach to generate modular fibrous architectures in 3D. Photo-cross-linkable polymers were electrospun, photopatterned into desired lengths, and coencapsulated alongside cells within natural biopolymer, semisynthetic, and synthetic hydrogels. Cells encapsulated within fiber-reinforced hydrogel composites (FHCs) demonstrated accelerated spreading rates compared to in gels lacking such fibrous topography. Furthermore, increases in fiber density at constant bulk hydrogel elastic modulus produced morphologically distinct cell populations and modulated cellular mechanosensing in 3D, as evidenced by increased nuclear localization of the mechanosensitive transcription factor, Yes-associated protein (YAP). This work documents the impact of physical guidance cues in 3D and establishes a novel approach to generating more physiologic tissue- and disease-specific biomimetic models.