Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania.
Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania; BioFrontiers Institute, University of Colorado Boulder; Department of Chemical and Biological Engineering, College of Engineering and Applied Science, University of Colorado Boulder;
J Vis Exp. 2022 May 17(183). doi: 10.3791/63867.
Granular hydrogels are jammed assemblies of hydrogel microparticles (i.e., "microgels"). In the field of biomaterials, granular hydrogels have many advantageous properties, including injectability, microscale porosity, and tunability by mixing multiple microgel populations. Methods to fabricate microgels often rely on water-in-oil emulsions (e.g., microfluidics, batch emulsions, electrospraying) or photolithography, which may present high demands in terms of resources and costs, and may not be compatible with many hydrogels. This work details simple yet highly effective methods to fabricate microgels using extrusion fragmentation and to process them into granular hydrogels useful for biomedical applications (e.g., 3D printing inks). First, bulk hydrogels (using photocrosslinkable hyaluronic acid (HA) as an example) are extruded through a series of needles with sequentially smaller diameters to form fragmented microgels. This microgel fabrication technique is rapid, low-cost, and highly scalable. Methods to jam microgels into granular hydrogels by centrifugation and vacuum-driven filtration are described, with optional post-crosslinking for hydrogel stabilization. Lastly, granular hydrogels fabricated from fragmented microgels are demonstrated as extrusion printing inks. While the examples described herein use photocrosslinkable HA for 3D printing, the methods are easily adaptable for a wide variety of hydrogel types and biomedical applications.
颗粒状水凝胶是水凝胶微球（即“微凝胶”）的被阻塞的组装体。在生物材料领域，颗粒状水凝胶具有许多有利的特性，包括可注射性、微尺度孔隙率和通过混合多种微凝胶群体的可调变性。制造微凝胶的方法通常依赖于水包油乳液（例如，微流控、批量乳液、静电喷雾）或光刻技术，这可能在资源和成本方面提出很高的要求，并且可能与许多水凝胶不兼容。这项工作详细介绍了使用挤出破碎制造微凝胶的简单而高效的方法，并将其加工成适用于生物医学应用的颗粒状水凝胶（例如，3D 打印墨水）。首先，将块状水凝胶（以光交联透明质酸（HA）为例）通过一系列直径逐渐减小的针挤出，形成碎片化的微凝胶。这种微凝胶制造技术快速、低成本且具有高度可扩展性。描述了通过离心和真空驱动过滤将微凝胶堵塞成颗粒状水凝胶的方法，并可选地进行后交联以稳定水凝胶。最后，展示了由碎片化微凝胶制成的颗粒状水凝胶作为挤出打印墨水的用途。虽然本文所述的示例使用光交联透明质酸用于 3D 打印，但这些方法很容易适应各种水凝胶类型和生物医学应用。
