Aliabouzar Mitra, Davidson Christopher D, Wang William Y, Kripfgans Oliver D, Franceschi Renny T, Putnam Andrew J, Fowlkes J Brian, Baker Brendon M, Fabiilli Mario L
Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Soft Matter. 2020 Jul 22;16(28):6501-6513. doi: 10.1039/d0sm00753f.
Acoustically-responsive scaffolds (ARSs), which are composite fibrin hydrogels, have been used to deliver regenerative molecules. ARSs respond to ultrasound in an on-demand, spatiotemporally-controlled manner via a mechanism termed acoustic droplet vaporization (ADV). Here, we study the ADV-induced, time-dependent micromechanical and microstructural changes to the fibrin matrix in ARSs using confocal fluorescence microscopy as well as atomic force microscopy. ARSs, containing phase-shift double emulsion (PSDE, mean diameter: 6.3 μm), were exposed to focused ultrasound to generate ADV - the phase transitioning of the PSDE into gas bubbles. As a result of ADV-induced mechanical strain, localized restructuring of fibrin occurred at the bubble-fibrin interface, leading to formation of locally denser regions. ADV-generated bubbles significantly reduced fibrin pore size and quantity within the ARS. Two types of ADV-generated bubble responses were observed in ARSs: super-shelled spherical bubbles, with a growth rate of 31 μm per day in diameter, as well as fluid-filled macropores, possibly as a result of acoustically-driven microjetting. Due to the strain stiffening behavior of fibrin, ADV induced a 4-fold increase in stiffness in regions of the ARS proximal to the ADV-generated bubble versus distal regions. These results highlight that the mechanical and structural microenvironment within an ARS can be spatiotemporally modulated using ultrasound, which could be used to control cellular processes and further the understanding of ADV-triggered drug delivery for regenerative applications.
声学响应支架（ARSs）是复合纤维蛋白水凝胶，已被用于递送再生分子。ARSs通过一种称为声滴汽化（ADV）的机制，以按需、时空可控的方式对超声波作出响应。在这里，我们使用共聚焦荧光显微镜和原子力显微镜研究了ADV诱导的、随时间变化的ARSs中纤维蛋白基质的微观力学和微观结构变化。含有相移双乳液（PSDE，平均直径：6.3μm）的ARSs被暴露于聚焦超声以产生ADV——PSDE向气泡的相转变。由于ADV诱导的机械应变，在气泡-纤维蛋白界面处发生了纤维蛋白的局部重组，导致形成局部更致密的区域。ADV产生的气泡显著减小了ARS内纤维蛋白的孔径和数量。在ARSs中观察到两种类型的ADV产生的气泡响应：超壳球形气泡，直径每天增长31μm，以及可能是由声驱动微喷射导致的充满液体的大孔。由于纤维蛋白的应变硬化行为，与远端区域相比，ADV在ARS中靠近ADV产生的气泡的区域诱导硬度增加了4倍。这些结果突出表明，ARS内的机械和结构微环境可以通过超声进行时空调节，可以用于控制细胞过程，并进一步理解ADV触发的用于再生应用的药物递送。
