Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, P. R. China.
Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, 100084, P. R. China.
Adv Healthc Mater. 2020 Dec;9(24):e2000782. doi: 10.1002/adhm.202000782. Epub 2020 Aug 12.
Despite progress in engineering both vascularized tissues and oriented tissues, the fabrication of 3D vascularized oriented tissues remains a challenge due to an inability to successfully integrate vascular and anisotropic structures that can support mass transfer and guide cell alignment, respectively. More importantly, there is a lack of an effective approach to guiding the scaffold design bearing both structural features. Here, an approach is presented to optimize the bifurcated channels within an anisotropic scaffold based on oxygen transport simulation and biological experiments. The oxygen transport simulation is performed using the experimentally measured effective oxygen diffusion coefficient and hydraulic permeability of the anisotropic scaffolds, which are also seeded with muscle precursor cells and cultured in a custom-made perfusion bioreactor. Symmetric bifurcation model is used as fractal unit to design the channel network based on biomimetic principles. The bifurcation level of channel network is further optimized based on the oxygen transport simulation, which is then validated by DNA quantification assay and pimonidazole immunostaining. This study provides a practical guide to optimizing bifurcated channels in anisotropic scaffolds for oriented tissue engineering.
尽管在构建血管化组织和各向异性组织方面取得了进展，但由于无法成功整合分别可支持传质和引导细胞排列的血管和各向异性结构，因此仍然难以制造 3D 血管化各向异性组织。更重要的是，缺乏一种有效的方法来指导同时具有结构特征的支架设计。在这里，提出了一种基于氧传输模拟和生物实验来优化各向异性支架内分叉通道的方法。使用实验测量的各向异性支架的有效氧扩散系数和水力渗透率进行氧传输模拟，这些支架还接种了肌肉前体细胞，并在定制的灌注生物反应器中培养。对称分叉模型被用作基于仿生原理设计通道网络的分形单元。根据氧传输模拟进一步优化通道网络的分叉水平，然后通过 DNA 定量分析和 pimonidazole 免疫染色进行验证。本研究为优化各向异性支架中的分叉通道以用于定向组织工程提供了实用指南。
