Astrab Leilani R, Hannan Riley T, Skelton Mackenzie L, Sturek Jeffrey M, Caliari Steven R
bioRxiv. 2025 Sep 11:2025.09.06.674583. doi: 10.1101/2025.09.06.674583.
In pulmonary fibrosis, excessive scar tissue accumulates in the alveolar interstitial space, impairing gas exchange and compromising lung function. This fibrotic remodeling results in tissue stiffening, but more complex lung mechanical properties critical to tissue function, such as viscoelasticity and stress relaxation, remain poorly defined. To address this gap, we use the bleomycin aged mouse model to characterize both bulk and spatially-resolved viscoelastic mechanical properties of normal and fibrotic lungs. Our analysis reveals that while bleomycin-induced fibrosis leads to heterogeneously increased lung stiffness, viscoelasticity as measured by tan delta (ratio of loss to storage modulus) and stress relaxation timescales remains remarkably consistent as a function of both age and bleomycin treatment. This unexpected preservation of viscoelasticity despite fibrotic stiffening highlights a previously underappreciated mechanical phenotype of fibrotic lungs. To model these distinct mechanical features , we utilize a hyaluronic acid-based hydrogel system that largely recapitulates the viscoelastic mechanical properties observed in both normal and fibrotic lungs. These findings provide new insight into the mechanical consequences of fibrosis and establish a tunable hydrogel platform mimicking key tissue viscoelastic properties.
在肺纤维化中，过多的瘢痕组织积聚在肺泡间质空间，损害气体交换并损害肺功能。这种纤维化重塑导致组织变硬，但对组织功能至关重要的更复杂的肺力学特性，如粘弹性和应力松弛，仍定义不清。为了填补这一空白，我们使用博来霉素老化小鼠模型来表征正常和纤维化肺的整体和空间分辨的粘弹性力学特性。我们的分析表明，虽然博来霉素诱导的纤维化导致肺硬度异质性增加，但用损耗角正切（损耗模量与储能模量之比）和应力松弛时间尺度测量的粘弹性作为年龄和博来霉素治疗的函数仍然非常一致。尽管纤维化变硬，但粘弹性的这种意外保留突出了纤维化肺以前未被充分认识的力学表型。为了模拟这些不同的力学特征，我们使用了一种基于透明质酸的水凝胶系统，该系统在很大程度上概括了在正常和纤维化肺中观察到的粘弹性力学特性。这些发现为纤维化的力学后果提供了新的见解，并建立了一个模拟关键组织粘弹性特性的可调水凝胶平台。
