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Bio-ink properties and printability for extrusion printing living cells

机译:挤出印刷活细胞的生物墨水特性和可印刷性

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Additive biofabrication (3D bioprinting) makes it possible to create scaffolds with precise geometries, control over pore interconnectivity and architectures that are not possible with conventional techniques. Inclusion of cells within the ink to form a "bio-ink" presents the potential to print 3D structures that can be implanted into damaged/diseased tissue to promote highly controlled cell-based regeneration and repair. The properties of an 'ink' are defined by its formulation and critically influence the delivery and integrity of structure formed. Importantly, the ink properties need to conform to biological requirements necessary for the cell system that they are intended to support and it is often challenging to find conditions for printing that facilitate this critical aspect of tissue bioengineering. In this study, alginate (Alg) was selected as the major component of the 'bio-ink' formulations for extrusion printing of cells. The rheological properties of alginate-gelatin (Alg-Gel) blends were compared with pre-crosslinked alginate and alginate solution to establish their printability whilst maintaining their ability to support optimal cell growth. Pre-crosslinked alginate on its own was liquid-like during printing. However, by controlling the temperature, Alg-Gel formulations had higher viscosity, storage modulus and consistency which facilitated higher print resolution/precision. Compression and indentation testing were used to examine the mechanical properties of alginate compared to Alg-Gel. Both types of gels yielded similar results with modulus increasing with alginate concentration. Decay in mechanical properties over time suggests that Alg-Gel slowly degrades in cell culture media with more than 60% decrease in initial modulus over 7 days. The viability of primary myoblasts delivered as a myoblast/Alg-Gel bio-ink was not affected by the printing process, indicating that the Alg-Gel matrix provides a potential means to print 3D constructs that may find application in myoregenerative applications.
机译:附加生物制造(3D生物打印)使创建具有精确几何形状的支架,控制孔的互连性和传统技术无法实现的架构成为可能。将细胞包含在墨水中以形成“生物墨水”具有打印3D结构的潜力,该3D结构可以植入受损/患病的组织中,以促进高度受控的基于细胞的再生和修复。 “油墨”的性质由其配方定义,并严重影响所形成结构的传递和完整性。重要的是,油墨特性需要符合它们打算支持的细胞系统所必需的生物学要求,而寻找有助于组织生物工程这一关键方面的印刷条件通常是具有挑战性的。在这项研究中,藻酸盐(Alg)被选作“生物墨水”配方的主要成分,用于细胞的挤压印刷。将藻酸盐-明胶(Alg-Gel)混合物的流变特性与预交联的藻酸盐和藻酸盐溶液进行比较,以建立其可印刷性,同时保持其支持最佳细胞生长的能力。预交联的藻酸盐本身在印刷过程中呈液体状。但是,通过控制温度,Alg-Gel配方具有更高的粘度,储能模量和稠度,从而有助于更高的打印分辨率/精度。与Alg-Gel相比,压缩和压痕测试用于检查藻酸盐的机械性能。两种类型的凝胶均产生相似的结果,其模量随藻酸盐浓度的增加而增加。机械性能随时间下降表明Alg-Gel在细胞培养基中缓慢降解,初始模量在7天内降低了60%以上。作为成肌细胞/ Alg-Gel生物墨水交付的原始成肌细胞的生存力不受印刷过程的影响,这表明Alg-Gel基质提供了一种潜在的手段来印刷可能在肌再生应用中发现的3D构建体。

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