Hiscox Colin, Li Juanyong, Gao Ziyang, Korkin Dmitry, Furlong Cosme, Billiar Kristen
Mechanical Engineering Department, Worcester Polytechnic Institute, Worcester, Massachusetts 01609, United States.
Biomedical Engineering Department, Worcester Polytechnic Institute, Worcester, Massachusetts 01609, United States.
ACS Biomater Sci Eng. 2025 Feb 10;11(2):1051-1059. doi: 10.1021/acsbiomaterials.4c01503. Epub 2025 Jan 15.
Mechanical properties of engineered connective tissues are critical for their success, yet modern sensors that measure physical qualities of tissues for quality control are invasive and destructive. The goal of this work was to develop a noncontact, nondestructive method to measure mechanical attributes of engineered skin substitutes during production without disturbing the sterile culture packaging. We optimized a digital holographic vibrometry (DHV) system to measure the mechanical behavior of Apligraf living cellular skin substitute through the clear packaging in multiple conditions: resting on solid agar as when the tissue is shipped, on liquid media in which it is grown, and freely suspended in air as occurs when the media is removed for feeding. We utilized full-field measurement to assess the complete surface deformation pattern to compare with vibration theory and found the patterns observed in air showed the closest behavior to theory. To simulate the effects of the actual culture dish geometry and the trilayer composition of the tissue on the porous membrane support, we employed finite element (FE) analysis. To simulate changes in thickness and stiffness that may occur with manufacturing process variations, we dried samples over time and observed measurable increases in the fundamental mode frequency which could be predicted by altering the thickness of the tissue layers in the FE model. However, quantitative estimates of the engineered tissue stiffness based on vibration theory are unrealistically high due to the signal being dominated by the stiff underlying membrane on which the tissue is cultured. Thus, although DHV is not able to specifically quantify the thickness or modulus or identify small spot defects, it has the potential to be used assess the overall properties of a tissue in-line and noninvasively for quality control.
工程化结缔组织的力学性能对其成功应用至关重要，然而，用于质量控制以测量组织物理特性的现代传感器具有侵入性且具有破坏性。这项工作的目标是开发一种非接触、无损的方法，在生产过程中测量工程化皮肤替代物的力学属性，同时不干扰无菌培养包装。我们优化了一种数字全息振动测量（DHV）系统，以在多种条件下通过透明包装测量Apligraf活性细胞皮肤替代物的力学行为：放置在固体琼脂上（如组织运输时的状态）、在其生长的液体培养基中以及在去除培养基进行喂食时自由悬浮于空气中。我们利用全场测量来评估完整的表面变形模式，以便与振动理论进行比较，发现空气中观察到的模式与理论行为最为接近。为了模拟实际培养皿几何形状以及组织在多孔膜支架上的三层结构的影响，我们采用了有限元（FE）分析。为了模拟制造过程变化可能导致的厚度和刚度变化，我们随时间干燥样品，并观察到基模频率有可测量的增加，这可以通过改变有限元模型中组织层的厚度来预测。然而，基于振动理论对工程化组织刚度的定量估计过高，不切实际，因为信号主要由组织所培养的坚硬底层膜主导。因此，尽管DHV无法具体量化厚度或模量，也无法识别小的点状缺陷，但它有潜力用于在线、非侵入性地评估组织的整体属性以进行质量控制。
