Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, United States.
Department of Biomedical Engineering, Columbia University, New York, NY, United States.
Acta Biomater. 2021 Sep 1;131:370-380. doi: 10.1016/j.actbio.2021.06.037. Epub 2021 Jun 27.
In living tissues, mechanical stiffness and biological function are intrinsically linked. Alterations in the stiffness of tissues can induce pathological interactions that affect cellular activity and tissue function. Underlying connections between tissue stiffness and disease highlights the importance of accurate quantitative characterizations of soft tissue mechanics, which can improve our understanding of disease and inform therapeutic development. In particular, accurate measurement of lung mechanical properties has been especially challenging due to the anatomical and mechanobiological complexities of the lung. Discrepancies between measured mechanical properties of dissected lung tissue samples and intact lung tissues in vivo has limited the ability to accurately characterize integral lung mechanics. Here, we report a non-destructive vacuum-assisted method to evaluate mechanical properties of soft biomaterials, including intact tissues and hydrogels. Using this approach, we measured elastic moduli of rat lung tissue that varied depending on stress-strain distribution throughout the lung. We also observed that the elastic moduli of enzymatically disrupted lung parenchyma increased by at least 64%. The reported methodology enables assessment of the nonlinear viscoelastic characteristics of intact lungs under normal and abnormal (i.e., injured, diseased) conditions and allows measurement of mechanical properties of tissue-mimetic biomaterials for use in therapeutics or in vitro models. STATEMENT OF SIGNIFICANCE: Accurate quantification of tissue stiffness is critical for understanding mechanisms of disease and developing effective therapeutics. Current modalities to measure tissue stiffness are destructive and preclude accurate assessment of lung mechanical properties, as lung mechanics are determined by complex features of the intact lung. To address the need for alternative methods to assess lung mechanics, we report a non-destructive vacuum-based approach to quantify tissue stiffness. We applied this method to correlate lung tissue mechanics with tissue disruption, and to assess the stiffness of biomaterials. This method can be used to inform the development of tissue-mimetic materials for use in therapeutics and disease models, and could potentially be applied for in-situ evaluation of tissue stiffness as a diagnostic or prognostic tool.
在活体组织中，力学硬度和生物学功能是内在相关的。组织硬度的改变会引起病理性相互作用，影响细胞活动和组织功能。组织硬度与疾病之间的潜在联系突显了准确量化软组织力学特性的重要性，这可以增进我们对疾病的理解并为治疗方法的开发提供信息。特别是，由于肺的解剖和力学生物学复杂性，准确测量肺的力学特性一直是一项挑战。在体完整肺组织和离体肺组织的力学特性测量之间的差异限制了对整体肺力学的准确描述。在这里，我们报告了一种非破坏性的真空辅助方法来评估软生物材料的力学特性，包括完整组织和水凝胶。使用这种方法，我们测量了大鼠肺组织的弹性模量，这些弹性模量随肺内的应力-应变分布而变化。我们还观察到，经酶处理破坏的肺实质的弹性模量增加了至少 64%。所报道的方法学能够评估正常和异常（即受伤、患病）条件下完整肺的非线性粘弹性特性，并允许测量用于治疗或体外模型的组织模拟生物材料的机械性能。
准确量化组织硬度对于理解疾病机制和开发有效的治疗方法至关重要。目前测量组织硬度的方法是破坏性的，无法准确评估肺的力学特性，因为肺力学是由完整肺的复杂特征决定的。为了解决需要替代方法来评估肺力学的问题，我们报告了一种非破坏性的基于真空的方法来量化组织硬度。我们将该方法应用于将肺组织力学与组织破坏相关联，并评估生物材料的硬度。该方法可用于为治疗和疾病模型中使用的组织模拟材料的开发提供信息，并且可以潜在地应用于作为诊断或预后工具的组织硬度的原位评估。
