Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, United States.
Biomaterials. 2010 Jul;31(21):5491-7. doi: 10.1016/j.biomaterials.2010.03.031. Epub 2010 May 5.
Development of robust 3D tissue analogs in vitro is limited by passive, diffusional mass transport. Perfused microfluidic tissue engineering scaffolds hold the promise to improve mass transport limitations and promote the development of complex, metabolically dense, and clinically relevant tissues. We report a simple and robust multilayer replica molding technique in which poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) diacrylate (PEGDA) are serially replica molded to develop microfluidic PEGDA hydrogel networks embedded within independently fabricated PDMS housings. We demonstrate the ability to control solute-scaffold effective diffusivity as a function of solute molecular weight and hydrogel concentration. Within cell laden microfluidic hydrogels, we demonstrate increased cellular viability in perfused hydrogel systems compared to static controls. We observed a significant increase in cell viability at all time points greater than zero at distances up to 1 mm from the perfused channel. Knowledge of spatiotemporal mass transport and cell viability gradients provides useful engineering design parameters necessary to maximize overall scaffold viability and metabolic density. This work has applications in the development of hydrogels as in vitro diagnostics and ultimately as regenerative medicine based therapeutics.
体外构建稳健的 3D 组织模拟物受到被动扩散传质的限制。灌注微流控组织工程支架有望改善传质限制并促进复杂、代谢密集和临床相关组织的发展。我们报告了一种简单而稳健的多层复制成型技术,其中聚二甲基硅氧烷(PDMS)和聚乙二醇二丙烯酸酯(PEGDA)依次进行复制成型,以开发微流控 PEGDA 水凝胶网络,该网络嵌入独立制造的 PDMS 外壳中。我们证明了可以控制溶质-支架有效扩散系数作为溶质分子量和水凝胶浓度的函数。在细胞负载微流控水凝胶中,与静态对照相比,在灌注水凝胶系统中观察到细胞活力增加。在距离灌注通道 1 毫米以内的所有时间点上,我们观察到细胞活力显著增加,超过零。了解时空传质和细胞活力梯度为最大限度地提高整体支架活力和代谢密度提供了有用的工程设计参数。这项工作在开发体外诊断用水凝胶以及最终开发基于再生医学的治疗方法方面具有应用前景。