Davidson Matthew D, Prendergast Margaret E, Ban Ehsan, Xu Karen L, Mickel Gabriel, Mensah Patricia, Dhand Abhishek, Janmey Paul A, Shenoy Vivek B, Burdick Jason A
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sci Adv. 2021 Nov 12;7(46):eabi8157. doi: 10.1126/sciadv.abi8157. Epub 2021 Nov 10.
The natural extracellular matrix (ECM) within tissues is physically contracted and remodeled by cells, allowing the collective shaping of functional tissue architectures. Synthetic materials that facilitate self-assembly similar to natural ECM are needed for cell culture, tissue engineering, and in vitro models of development and disease. To address this need, we develop fibrous hydrogel assemblies that are stabilized with photocrosslinking and display fiber density–dependent strain-responsive properties (strain stiffening and alignment). Encapsulated mesenchymal stromal cells locally contract low fiber density assemblies, resulting in macroscopic volumetric changes with increased cell densities and moduli. Because of properties such as shear-thinning and self-healing, assemblies can be processed into microtissues with aligned ECM deposition or through extrusion bioprinting and photopatterning to fabricate constructs with programmed shape changes due to cell contraction. These materials provide a synthetic approach to mimic features of natural ECM, which can now be processed for applications in biofabrication and tissue engineering.
组织内的天然细胞外基质（ECM）会被细胞进行物理收缩和重塑，从而实现功能性组织结构的整体塑造。细胞培养、组织工程以及发育和疾病的体外模型需要能够促进类似于天然ECM的自组装的合成材料。为满足这一需求，我们开发了通过光交联稳定且具有纤维密度依赖性应变响应特性（应变硬化和排列）的纤维水凝胶组件。封装的间充质基质细胞会局部收缩低纤维密度组件，导致随着细胞密度和模量增加出现宏观体积变化。由于具有剪切变稀和自愈等特性，组件可以加工成具有对齐ECM沉积的微组织，或通过挤出生物打印和光图案化来制造因细胞收缩而具有编程形状变化的构建体。这些材料提供了一种模拟天然ECM特征的合成方法，现在可将其加工用于生物制造和组织工程应用。
