Hong Xiaowei, Stegemann Jan P, Deng Cheri X
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2099, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2099, USA.
Biomaterials. 2016 May;88:12-24. doi: 10.1016/j.biomaterials.2016.02.019. Epub 2016 Feb 18.
Characterization of the microscale mechanical properties of biomaterials is a key challenge in the field of mechanobiology. Dual-mode ultrasound elastography (DUE) uses high frequency focused ultrasound to induce compression in a sample, combined with interleaved ultrasound imaging to measure the resulting deformation. This technique can be used to non-invasively perform creep testing on hydrogel biomaterials to characterize their viscoelastic properties. DUE was applied to a range of hydrogel constructs consisting of either hydroxyapatite (HA)-doped agarose, HA-collagen, HA-fibrin, or preosteoblast-seeded collagen constructs. DUE provided spatial and temporal mapping of local and bulk displacements and strains at high resolution. Hydrogel materials exhibited characteristic creep behavior, and the maximum strain and residual strain were both material- and concentration-dependent. Burger's viscoelastic model was used to extract characteristic parameters describing material behavior. Increased protein concentration resulted in greater stiffness and viscosity, but did not affect the viscoelastic time constant of acellular constructs. Collagen constructs exhibited significantly higher modulus and viscosity than fibrin constructs. Cell-seeded collagen constructs became stiffer with altered mechanical behavior as they developed over time. Importantly, DUE also provides insight into the spatial variation of viscoelastic properties at sub-millimeter resolution, allowing interrogation of the interior of constructs. DUE presents a novel technique for non-invasively characterizing hydrogel materials at the microscale, and therefore may have unique utility in the study of mechanobiology and the characterization of hydrogel biomaterials.
生物材料微观力学性能的表征是力学生物学领域的一项关键挑战。双模超声弹性成像（DUE）使用高频聚焦超声在样品中诱导压缩，并结合交错超声成像来测量由此产生的变形。该技术可用于对水凝胶生物材料进行非侵入性蠕变测试，以表征其粘弹性特性。DUE被应用于一系列水凝胶构建体，这些构建体由羟基磷灰石（HA）掺杂的琼脂糖、HA-胶原蛋白、HA-纤维蛋白或接种前成骨细胞的胶原蛋白构建体组成。DUE以高分辨率提供了局部和整体位移及应变的空间和时间映射。水凝胶材料表现出特征性的蠕变行为，最大应变和残余应变均取决于材料和浓度。使用伯格斯粘弹性模型提取描述材料行为的特征参数。蛋白质浓度的增加导致刚度和粘度增加，但不影响无细胞构建体的粘弹性时间常数。胶原蛋白构建体的模量和粘度明显高于纤维蛋白构建体。随着时间的推移，接种细胞的胶原蛋白构建体在发育过程中变得更硬，力学行为也发生了改变。重要的是，DUE还能洞察亚毫米分辨率下粘弹性特性的空间变化，从而能够对构建体内部进行研究。DUE提出了一种在微观尺度上对水凝胶材料进行非侵入性表征的新技术，因此在力学生物学研究和水凝胶生物材料表征方面可能具有独特的用途。
