1 Department of Bioengineering, Stanford University , Stanford, California.
2 Department of Orthopaedic Surgery, Stanford University , Stanford, California.
Tissue Eng Part A. 2018 Jan;24(1-2):1-10. doi: 10.1089/ten.TEA.2016.0453. Epub 2017 Aug 22.
Zonal organization plays an important role in cartilage structure and function, whereas most tissue-engineering strategies developed to date have only allowed the regeneration of cartilage with homogeneous biochemical and mechanical cues. To better restore tissue structure and function, there is a strong need to engineer materials with biomimetic gradient niche cues that recapitulate native tissue organization. To address this critical unmet need, in this study, we report a method for rapid formation of tissue-scale gradient hydrogels as a three-dimensional (3D) cell niche with tunable biochemical and physical properties. When encapsulated in stiffness gradient hydrogels, both chondrocytes and mesenchymal stem cells demonstrated zone-specific response and extracellular deposition that mimics zonal organization of articular cartilage. Blocking cell mechanosensing using blebbistatin abolished the zonal response of chondrocytes in 3D hydrogels with a stiffness gradient. Such tissue-scale gradient hydrogels can provide a 3D artificial cell niche to enable tissue engineering of various tissue types with zonal organizations or tissue interfaces.
分区组织在软骨结构和功能中起着重要作用，而迄今为止开发的大多数组织工程策略仅允许具有均质生化和机械线索的软骨再生。为了更好地恢复组织结构和功能，强烈需要工程材料具有仿生梯度生态位线索，以再现天然组织组织。为了解决这一关键的未满足需求，在本研究中，我们报告了一种快速形成组织尺度梯度水凝胶的方法，作为具有可调生化和物理性质的三维（3D）细胞生态位。当包封在刚度梯度水凝胶中时，软骨细胞和间充质干细胞均表现出与关节软骨分区组织相似的区特异性反应和细胞外沉积。使用 blebbistatin 阻断细胞机械感受会消除具有刚度梯度的 3D 水凝胶中软骨细胞的分区反应。这种组织尺度梯度水凝胶可以提供 3D 人工细胞生态位，从而能够对具有分区组织或组织界面的各种组织类型进行组织工程。
