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将 4D 技术融入生物打印:实时磁导向胶原纤维排列以生成复杂的多层组织。

Incorporating 4D into Bioprinting: Real-Time Magnetically Directed Collagen Fiber Alignment for Generating Complex Multilayered Tissues.

机构信息

Department of Orthopaedics, RWTH Aachen University Hospital, 52074, Aachen, Germany.

Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, 52074, Aachen, Germany.

出版信息

Adv Healthc Mater. 2018 Nov;7(21):e1800894. doi: 10.1002/adhm.201800894. Epub 2018 Sep 17.

DOI:10.1002/adhm.201800894
PMID:30221829
Abstract

In vitro multilayered tissues with mimetic architectures resembling native tissues are valuable tools for application in medical research. In this study, an advanced bioprinting strategy is presented for aligning collagen fibers contained in functional bioinks. Streptavidin-coated iron nanoparticles are embedded in printable bioinks with varying concentrations of low gelling temperature agarose and type I collagen. By applying a straightforward magnetic-based mechanism in hydrogels during bioprinting, it is possible to align collagen fibers in less concentrated hydrogel blends with a maximum agarose concentration of 0.5 w/v%. Conversely, more elevated concentrations of agarose in printable blends show random collagen fiber distribution. Interestingly, hydrogel blends with unidirectionally aligned collagen fibers show significantly higher compression moduli compared to hydrogel blends including random fibers. Considering its application in the field of cartilage tissue engineering, bioprinted constructs with alternating layers of aligned and random fibers are fabricated. After 21 days of culture, cell-loaded constructs with alternating layers of aligned and random fibers express markedly more collagen II in comparison to solely randomly oriented fiber constructs. These encouraging results translate the importance of the structure and architecture of bioinks used in bioprinting in light of their use for tissue engineering and personalized medical applications.

摘要

具有类似天然组织仿生结构的体外多层组织是医学研究应用的有价值工具。在这项研究中,提出了一种先进的生物打印策略,用于对齐功能性生物墨水所含的胶原纤维。链霉亲和素包被的铁纳米颗粒嵌入到琼脂糖和 I 型胶原浓度不同的可打印生物墨水中。通过在生物打印过程中在水凝胶中应用简单的基于磁场的机制,可以在琼脂糖浓度最高为 0.5 w/v%的低浓度水凝胶混合物中对齐胶原纤维。相反,在可打印混合物中更高浓度的琼脂糖显示出随机的胶原纤维分布。有趣的是,与包含随机纤维的水凝胶混合物相比,具有单向对齐胶原纤维的水凝胶混合物显示出明显更高的压缩模量。考虑到其在软骨组织工程领域的应用,制造了具有定向和随机纤维交替层的生物打印构建体。在培养 21 天后,与仅具有随机取向纤维的构建体相比,具有定向和随机纤维交替层的细胞负载构建体表达出明显更多的 II 型胶原。这些令人鼓舞的结果表明,生物墨水的结构和架构在生物打印中的重要性,考虑到它们在组织工程和个性化医疗应用中的用途。

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