Orthopaedic Bioengineering Research Laboratory, Department of Mechanical Engineering and School of Biomedical Engineering, Colorado State University, Ft Collins, CO, USA.
Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopaedic Surgery and Musculoskeletal Medicine, Centre for Bioengineering & Nanomedicine, University of Otago Christchurch, Christchurch, 8011, New Zealand.
J Mech Behav Biomed Mater. 2019 Oct;98:317-326. doi: 10.1016/j.jmbbm.2019.06.029. Epub 2019 Jun 29.
Tissue engineering strategies require the provision of a micromechanical state of stress that is conducive to the generation and maintenance of healthy mature tissue. Of particular interest, angle-ply biomimetic scaffolds augmented with cellular content have been proposed for annulus fibrosus (AF) engineering in order to repair the intervertebral disc. However, the influence of the inherent variability of fabricated constructs and physiological conditions on overall scaffold mechanics, micromechanical environment within the scaffold, and consequent cellular differentiation is relatively unknown. In this study, melt extrusion 3D fiber-deposition (3DF) was used to fabricate five different polycaprolactone angle-ply scaffold architectures which were subject to multiaxial tensile testing and linear elastic orthotropic constitutive fitting. All scaffold groups predicted stiffnesses similar to previously reported native AF moduli in biaxial and uniaxial tensile strain. However, no single scaffold group in this study simultaneously achieved all target AF mechanics in all loading regimes. In equibiaxial tension, the biaxial stiffness ratio of native AF (EE = 0.55 to 0.62) was predicted between fiber angles of 30° and 35°, which is similar to the collagen orientation in native AF. In global equibiaxial loading, an apparent asymptote in the transverse moduli (EE ranging -380 MPa to 700 MPa) was observed near the 40° fiber angle scaffolds in equibiaxial tensile strain, attributed to stiffening from the transverse loading. These results highlight that tissue engineering scaffold designs should target replication of physiologically-relevant native tissue mechanics and demonstrate the importance of designing constructs that are unaffected by anticipated variations in manufacturing and clinical application.
组织工程策略需要提供有利于生成和维持健康成熟组织的微机械状态的应力。特别感兴趣的是,已经提出了具有细胞内容物的角层仿生支架来增强纤维环(AF)工程,以修复椎间盘。然而,制造结构的固有可变性和生理条件对整体支架力学、支架内的微机械环境以及随后的细胞分化的影响还相对未知。在这项研究中,使用熔融挤出 3D 纤维沉积(3DF)来制造五种不同的聚己内酯角层支架结构,这些结构经受多轴拉伸测试和线性弹性各向异性本构拟合。所有支架组都预测出与之前在双轴和单轴拉伸应变中报告的天然 AF 模量相似的刚度。然而,在本研究中,没有一个支架组在所有加载状态下同时达到所有目标 AF 力学性能。在等双轴拉伸中,天然 AF 的双轴刚度比(EE=0.55 至 0.62)在纤维角度为 30°和 35°之间预测,这与天然 AF 中的胶原蛋白取向相似。在全局等双轴加载中,在等双轴拉伸应变中,接近 40°纤维角支架的横向模量(EE 范围为-380 MPa 至 700 MPa)出现明显的渐近线,这归因于横向加载引起的变硬。这些结果表明,组织工程支架设计应针对复制生理相关的天然组织力学性能,并证明设计不受制造和临床应用预期变化影响的构建体的重要性。