Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Acta Biomater. 2015 Jan;11:274-82. doi: 10.1016/j.actbio.2014.09.031. Epub 2014 Oct 1.
Engineered tissue microenvironments impart specialized cues that drive distinct cellular phenotypes and function. Microenvironments with defined properties, such as mechanical properties and fibril alignment, can elicit specific cellular responses that emulate those observed in vivo. Collagen- and glycosaminoglycan (GAG)-based tissue matrices have been popularized due to their biological ubiquity in a broad range of tissues and the ability to tune structure and mechanical properties through a variety of processes. Here, we investigate the combined effects of static magnetic fields, and GAG and cell encapsulation, on the structure (e.g. collagen fibril orientation) and material properties of collagen matrices. We found that magnetic fields align the collagen-GAG matrix, alter equilibrium mechanical properties and provide a method for encapsulating cells within a three-dimensional aligned matrix. Cells are encapsulated prior to polymerization, allowing for controlled cell density and eliminating the need for cell seeding. Increased relative GAG concentrations reduced the ability to magnetically align collagen fibrils, in part through a mechanism involving increased viscosity and polymerization time of the collagen-GAG solution. This work provides a functional design space for the development of pure collagen and hybrid collagen-GAG matrices in the presence of magnetic fields. Additionally, this work shows that magnetic fields are effective for the fabrication of collagen constructs with controlled fibril orientation, and can be coupled with GAG incorporation to modulate mechanical properties and the response of embedded cells.
工程化组织微环境赋予特定的线索，从而驱动独特的细胞表型和功能。具有明确特性的微环境，如机械特性和纤维排列，可以引发特定的细胞反应，模拟体内观察到的反应。由于胶原蛋白和糖胺聚糖 (GAG) 在广泛的组织中具有生物普遍性，并且能够通过多种方法调整结构和机械特性，因此基于胶原蛋白和 GAG 的组织基质已经得到了广泛应用。在这里，我们研究了静态磁场、GAG 和细胞包封对胶原蛋白基质的结构（例如胶原蛋白纤维排列）和材料特性的综合影响。我们发现磁场可以使胶原蛋白-GAG 基质排列，改变平衡机械性能，并为在三维排列基质中封装细胞提供一种方法。细胞在聚合之前被封装，从而可以控制细胞密度，并消除细胞接种的需要。相对 GAG 浓度的增加降低了磁场使胶原蛋白纤维排列的能力，部分原因是涉及增加胶原蛋白-GAG 溶液的粘度和聚合时间的机制。这项工作为在磁场存在下开发纯胶原蛋白和混合胶原蛋白-GAG 基质提供了一个功能设计空间。此外，这项工作表明磁场可有效制造具有受控纤维排列的胶原蛋白结构，并可与 GAG 结合使用，以调节机械性能和嵌入细胞的反应。
