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定制化 3D 打印生物反应器用于去细胞化-高效且高质量,预算友好。

Customized 3D printed bioreactors for decellularization-High efficiency and quality on a budget.

机构信息

Department of Cardiac Surgery, Ludwig-Maximilian University, Munich, Germany.

Chair of Medical Materials and Implants, Technical University, Munich, Germany.

出版信息

Artif Organs. 2021 Dec;45(12):1477-1490. doi: 10.1111/aor.14034. Epub 2021 Jul 14.

Abstract

Decellularization (DC) of biomaterials with bioreactors is widely used to produce scaffolds for tissue engineering. This study uses 3D printing to develop efficient but low-cost DC bioreactors. Two bioreactors were developed to decellularize pericardial patches and vascular grafts. Flow profiles and pressure distribution inside the bioreactors were optimized by steady-state computational fluid dynamics (CFD) analysis. Printing materials were evaluated by cytotoxicity assessment. Following evaluation, all parts of the bioreactors were 3D printed in a commercial fused deposition modeling printer. Samples of bovine pericardia and porcine aortae were decellularized using established protocols. An immersion and agitation setup was used as a control. With histological assessment, DNA quantification and biomechanical testing treatment effects were evaluated. CFD analysis of the pericardial bioreactor revealed even flow and pressure distribution in between all pericardia. The CFD analysis of the vessel bioreactor showed increased intraluminal flow rate and pressure compared to the vessel's outside. Cytotoxicity assessment of the used printing material revealed no adverse effect on the tissue. Complete DC was achieved for all samples using the 3D printed bioreactors while DAPI staining revealed residual cells in aortic vessels of the control group. Histological analysis showed no structural changes in the decellularized samples. Additionally, biomechanical properties exhibited no significant change compared to native samples. This study presents a novel approach to manufacturing highly efficient and low budget 3D printed bioreactors for the DC of biomaterials. When compared to standard protocols, the bioreactors offer a cost effective, fast, and reproducible approach, which vastly improves the DC results.

摘要

使用生物反应器对生物材料进行脱细胞处理被广泛用于组织工程支架的制备。本研究使用 3D 打印技术开发高效但低成本的脱细胞生物反应器。开发了两种生物反应器来脱细胞化心包贴片和血管移植物。通过稳态计算流体动力学 (CFD) 分析优化了生物反应器内的流动剖面和压力分布。通过细胞毒性评估来评估打印材料。评估后,生物反应器的所有部件均在商业熔丝制造打印机中进行 3D 打印。使用已建立的方案对牛心包和猪主动脉样本进行脱细胞处理。使用浸入和搅拌装置作为对照。通过组织学评估、DNA 定量和生物力学测试评估处理效果。心包生物反应器的 CFD 分析显示,所有心包之间的流动和压力分布均匀。血管生物反应器的 CFD 分析显示,与血管外部相比,管腔内的流速和压力增加。所用打印材料的细胞毒性评估显示对组织无不良影响。使用 3D 打印生物反应器可实现所有样本的完全脱细胞化,而 DAPI 染色显示对照组主动脉中的残留细胞。组织学分析显示脱细胞化样本无结构变化。此外,与天然样本相比,生物力学特性没有明显变化。本研究提出了一种制造高效、低成本的 3D 打印生物反应器的新方法,用于生物材料的脱细胞处理。与标准方案相比,该生物反应器提供了一种具有成本效益、快速且可重复的方法,大大提高了脱细胞化效果。

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