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Bio-Design and Manufacturing  2022 Vol.5 No.3 P.512-528

http://doi.org/10.1007/s42242-022-00192-5


Droplet-based bioprinting enables the fabrication of cell–hydrogel–microfibre composite tissue precursors


Author(s):  Marcin Kotlarz, Ana M. Ferreira, Piergiorgio Gentile, Stephen J. Russell & Kenneth Dalgarno

Affiliation(s):  School of Engineering, Newcastle University, Newcastle upon Tyne NE1 7RU, UK; more

Corresponding email(s):   kenny.dalgarno@ncl.ac.uk

Key Words:  Bioprinting, Hydrogel–fibre composites, High-cell-density hydrogels, Composite manufacturing


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Marcin Kotlarz, Ana M. Ferreira, Piergiorgio Gentile, Stephen J. Russell & Kenneth Dalgarno. Droplet-based bioprinting enables the fabrication of cell–hydrogel–microfibre composite tissue precursors[J]. Journal of Zhejiang University Science D, 2022, 5(3): 512-528.

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Abstract: 
Composites offer the option of coupling the individual benefits of their constituents to achieve unique material properties, which can be of extra value in many tissue engineering applications. Strategies combining hydrogels with fibre-based scaffolds can create tissue constructs with enhanced biological and structural functionality. However, developing efficient and scalable approaches to manufacture such composites is challenging. Here, we use a droplet-based bioprinting system called reactive jet impingement (ReJI) to integrate a cell-laden hydrogel with a microfibrous mesh. This system uses microvalves connected to different bioink reservoirs and directed to continuously jet bioink droplets at one another in mid-air, where the droplets react and form a hydrogel that lands on a microfibrous mesh. Cell–hydrogel–fibre composites are produced by embedding human dermal fibroblasts at two different concentrations (5 × 106 and 30 × 106 cells/mL) in a collagen–alginate–fibrin hydrogel matrix and bioprinted onto a fibre-based substrate. Our results show that both types of cell–hydrogel–microfibre composite maintain high cell viability and promote cell–cell and cell–biomaterial interactions. The lower fibroblast density triggers cell proliferation, whereas the higher fibroblast density facilitates faster cellular organisation and infiltration into the microfibres. Additionally, the fibrous component of the composite is characterised by high swelling properties and the quick release of calcium ions. The data indicate that the created composite constructs offer an efficient way to create highly functional tissue precursors for laminar tissue engineering, particularly for wound healing and skin tissue engineering applications.

英国纽卡斯尔大学Kenneth Dalgarno等 | 基于液滴生物打印制造细胞-水凝胶-微纤维复合组织前体

本研究论文聚焦多液滴融合打印的技术创新与应用实例。复合材料能结合各组分材料优势实现独特的材料性能,在许多组织工程应用中具有特殊价值。将水凝胶和纤维支架相结合可以增强组织结构的生物和结构功能性,但开发有效且可扩展的方法用于制造此类复合材料存在挑战。本工作使用一种基于液滴的生物打印系统 (reactive jet impingement, ReJI) 将载细胞水凝胶与微纤维网络支架集成在一起。该打印系统的两个微阀式喷嘴分别连接至不同的生物墨水墨盒,产生对应墨水的液滴,液滴在空中碰撞融合后发生交联形成水凝胶,最后沉积至微纤维网上。以胶原蛋白-海藻酸钠-纤维蛋白水凝胶基质包裹两种不同浓度(5×106和30×106 cells/ml)的人真皮成纤维细胞作为生物墨水,生物打印到微纤维网络基底上制备出细胞-水凝胶-纤维复合材料。结果表明,这两种类型的细胞-水凝胶-微纤维复合材料保持了较高的细胞活性,并促进了细胞-细胞和细胞-生物材料相互作用。较低的成纤维细胞密度引发细胞增殖,而较高的成纤维细胞密度有助于细胞更快地组织和渗透到微纤维中。此外,复合材料的纤维成分具有高溶胀和快速释放钙离子的特性。本工作制造的复合结构为薄片状组织工程提供了一种制造高度功能性支架的方法,特别是伤口愈合和皮肤组织工程应用。

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