Tong Xinming, Jiang James, Zhu Danqing, Yang Fan
Department of Bioengineering, Stanford University School of Medicine, 300 Pasteur Drive, Edwards R105, Stanford, California 94305, United States.
ACS Biomater Sci Eng. 2016 May 9;2(5):845-852. doi: 10.1021/acsbiomaterials.6b00074. Epub 2016 Apr 11.
Cell niche is a multifactorial environment containing complex interactions between biochemical and physical cues. Although extensive studies have examined the effects of biochemical or physical cues alone on cell fate, how biochemical and mechanical signals interact to influence cell fates remains largely unknown. To address this challenge, here we report a polyethylene glycol-based gradient hydrogel platform as biomimetic cell niche containing independently tunable matrix stiffness and biochemical ligand density. The versatility of this platform is demonstrated by fabricating and characterizing single gradient or orthogonally aligned dual gradient hydrogels. These gradients result in differential elongation and spreading of human fibroblasts. Both hydrogel stiffness and biochemical ligand density are independently tunable by sequential photopolymerization. By controlling light exposure, a broad range of hydrogel stiffness and different types/doses of biochemical ligands can be incorporated. Such tunability facilitates customization of this platform for investigating complex cell-niche interactions associated with various cell types, such as stem cells and cancer cells. The outcomes of such studies may help identify optimal niche cues to promote desiralbe stem fates and tissue regeneration or inhibit diseases progression.
细胞微环境是一个多因素的环境，其中生化和物理信号之间存在复杂的相互作用。尽管已有广泛研究单独考察了生化或物理信号对细胞命运的影响，但生化和机械信号如何相互作用以影响细胞命运在很大程度上仍不清楚。为应对这一挑战，我们在此报告一种基于聚乙二醇的梯度水凝胶平台，作为一种仿生细胞微环境，其具有可独立调节的基质硬度和生化配体密度。通过制备和表征单梯度或正交排列的双梯度水凝胶，证明了该平台的多功能性。这些梯度导致人成纤维细胞的伸长和铺展存在差异。水凝胶硬度和生化配体密度均可通过顺序光聚合独立调节。通过控制光照，可以引入广泛范围的水凝胶硬度以及不同类型/剂量的生化配体。这种可调性有助于定制该平台，以研究与各种细胞类型（如干细胞和癌细胞）相关的复杂细胞-微环境相互作用。此类研究结果可能有助于确定最佳的微环境信号，以促进理想的干细胞命运和组织再生，或抑制疾病进展。
