Stornello Dean E, Kim Jun, Chen Zhiyuan, Heaton Kyle, Qazi Taimoor H
Weldon School of Biomedical Engineering, Purdue University, West Lafayette 47907-2050, Indiana, United States.
Department of Agricultural and Biological Engineering, Purdue University, West Lafayette 47907-2050, Indiana, United States.
ACS Biomater Sci Eng. 2025 Feb 10;11(2):1242-1252. doi: 10.1021/acsbiomaterials.4c02102. Epub 2025 Jan 9.
Granular hydrogels are injectable and inherently porous biomaterials assembled through the packing of microparticles. These particles typically have a symmetric and spherical shape. However, recent studies have shown that asymmetric particles with high aspect ratios, such as fibers and rods, can significantly improve the mechanics, structure, and cell-guidance ability of granular hydrogels. Despite this, it remains unknown how controlled changes in the particle aspect ratio influence the injectability, porosity, and cell-instructive capabilities of granular hydrogels. Part of the challenge lies in obtaining microparticles with precisely tailored dimensions using fabrication methods such as flow-focusing microfluidics or extrusion fragmentation. In this work, we leveraged facile photolithography and photocurable hyaluronic acid to fabricate rod-shaped microparticles with widths and heights of 130 μm and lengths that varied from 260 to 1300 μm to obtain aspect ratios (ARs) of 2, 4, 6, 8, and 10. All AR microparticles formed porous and injectable granular hydrogels after centrifugation jamming. Interestingly, the longest microparticles neither clogged the needle nor fractured after extrusion from a syringe. This was attributed to a relatively low elastic modulus that permitted microparticle pliability and reversible deformation under shear. Cells (NIH/3T3 fibroblasts) mixed with the jammed microparticles and injected into molds remained viable, adhered to the particles' surface, and showed a significant and rapid rate of proliferation over a period of 7 days compared to bulk hydrogels. The proliferation rate and morphology of the cells were significantly influenced by the particle AR, with higher cell numbers observed with intermediate ARs, likely attributable to the surface area available for cell adhesion. These findings showcase the utility of injectable granular hydrogels made with high-aspect-ratio microparticles for biomedical applications.
颗粒水凝胶是通过微粒堆积组装而成的可注射且具有固有孔隙的生物材料。这些颗粒通常呈对称球形。然而，最近的研究表明，具有高纵横比的不对称颗粒，如纤维和棒状颗粒，可显著改善颗粒水凝胶的力学性能、结构和细胞引导能力。尽管如此，颗粒纵横比的可控变化如何影响颗粒水凝胶的可注射性、孔隙率和细胞诱导能力仍不清楚。部分挑战在于使用诸如流动聚焦微流体或挤出破碎等制造方法来获得尺寸精确定制的微粒。在这项工作中，我们利用简便的光刻技术和光固化透明质酸制备了宽度和高度为130μm、长度在260至1300μm之间变化的棒状微粒，以获得纵横比为2、4、6、8和10的微粒。所有纵横比的微粒在离心挤压后均形成了多孔且可注射的颗粒水凝胶。有趣的是，最长的微粒在从注射器挤出后既不会堵塞针头也不会断裂。这归因于相对较低的弹性模量，该模量允许微粒在剪切作用下具有柔韧性和可逆变形。与细胞混合并注入模具中的细胞（NIH/3T3成纤维细胞）与挤压后的微粒混合后仍保持活力，附着在微粒表面，并且与块状水凝胶相比，在7天的时间内显示出显著且快速的增殖速率。细胞的增殖速率和形态受到颗粒纵横比的显著影响，中等纵横比时观察到的细胞数量更多，这可能归因于可用于细胞粘附的表面积。这些发现展示了由高纵横比微粒制成的可注射颗粒水凝胶在生物医学应用中的实用性。
