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基于新型天然高分子生物墨水的 3D 生物打印支架结构的设计与优化。

Design and optimization of 3D-bioprinted scaffold framework based on a new natural polymeric bioink.

机构信息

Department of Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia, Italy.

Department of Civil Engineering and Architecture, University of Pavia, Via Ferrata 5, 27100 Pavia, Italy.

出版信息

J Pharm Pharmacol. 2022 Jan 5;74(1):57-66. doi: 10.1093/jpp/rgab116.

Abstract

OBJECTIVES

This aimed at the design and production of engineered 3D scaffold prototypes using a natural polymeric bioink made of chitosan and poly-γ-glutamic acid with a specific focus on 3D-bioprinting process and on 3D framework geometry.

METHODS

Prototypes were produced using a 3D bioprinter exploiting layer-by-layer deposition technology. The 3D scaffold prototypes were fully characterized concerning pore size and size distribution, stability in different experimental conditions, swelling capability, and human dermal fibroblasts viability.

KEY FINDINGS

Hexagonal framework combined with biopaper allowed stabilizing the 3-layers structure during process manufacturing and during incubation in cell culture conditions. The stability of 3-layers structure was well preserved for 48 h. Crosslinking percentages of 2-layers and 3-layers prototype were 88.2 and 68.39, respectively. The swelling study showed a controlled swelling capability for 2-layers and 3-layers prototype, ∼5%. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed good biocompatibility of 3-layers prototype and their suitability for preserving 48 h cell viability in 3D cultures. Moreover, a significant increment of absorbance value was measured after 48 h, demonstrating cell growth.

CONCLUSIONS

Bioink obtained combining chitosan and poly-γ-glutamic acid represents a good option for 3D bioprinting. A stable 3D structure was realized by layer-by-layer deposition technology; compared with other papers, the present study succeeded in using medical healthcare-grade polymers, no-toxic crosslinker, and solvents according to ICH Topic Q3C (R4).

摘要

目的

本研究旨在设计和制作使用壳聚糖和聚-γ-谷氨酸天然聚合物生物墨水的工程 3D 支架原型,特别关注 3D 生物打印过程和 3D 框架几何形状。

方法

使用 3D 生物打印机通过逐层沉积技术来制作原型。对 3D 支架原型的孔径和孔径分布、在不同实验条件下的稳定性、溶胀性能以及人真皮成纤维细胞活力进行了全面的特性描述。

主要发现

六边形框架与生物纸结合,在制造过程中和在细胞培养条件下孵育时,可以稳定 3 层结构。48 小时内,3 层结构的稳定性得到了很好的保持。2 层和 3 层原型的交联率分别为 88.2%和 68.39%。溶胀研究表明,2 层和 3 层原型具有可控制的溶胀能力,约为 5%。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)检测结果表明,3 层原型具有良好的生物相容性,适合在 3D 培养中保持 48 小时的细胞活力。此外,在 48 小时后测量到吸光度值显著增加,证明了细胞的生长。

结论

壳聚糖和聚-γ-谷氨酸的组合生物墨水是 3D 生物打印的一个不错选择。通过逐层沉积技术实现了稳定的 3D 结构;与其他论文相比,本研究成功地使用了符合 ICH 主题 Q3C(R4)的医疗保健级聚合物、无毒交联剂和溶剂。

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