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微凝胶制备技术对颗粒水凝胶性能的影响。

Influence of Microgel Fabrication Technique on Granular Hydrogel Properties.

机构信息

Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

Department of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, 97070 Würzburg, Germany.

出版信息

ACS Biomater Sci Eng. 2021 Sep 13;7(9):4269-4281. doi: 10.1021/acsbiomaterials.0c01612. Epub 2021 Feb 16.

Abstract

Bulk hydrogels traditionally used for tissue engineering and drug delivery have numerous limitations, such as restricted injectability and a nanoscale porosity that reduces cell invasion and mass transport. An evolving approach to address these limitations is the fabrication of hydrogel microparticles (i.e., "microgels") that can be assembled into granular hydrogels. There are numerous methods to fabricate microgels; however, the influence of the fabrication technique on granular hydrogel properties is unexplored. Herein, we investigated the influence of three microgel fabrication techniques (microfluidic devices (MD), batch emulsions (BE), and mechanical fragmentation by extrusion (EF)) on the resulting granular hydrogel properties (e.g., mechanics, porosity, and injectability). Hyaluronic acid (HA) modified with various reactive groups (i.e., norbornenes (NorHA), pentenoates (HA-PA), and methacrylates (MeHA)) were used to form microgels with an average diameter of ∼100 μm. The MD method resulted in homogeneous spherical microgels, the BE method resulted in heterogeneous spherical microgels, and the EF method resulted in heterogeneous polygonal microgels. Across the various reactive groups, microgels fabricated with the MD and BE methods had lower functional group consumption when compared to microgels fabricated with the EF method. When microgels were jammed into granular hydrogels, the storage modulus (') of EF granular hydrogels (∼1000-3000 Pa) was consistently an order of magnitude higher than G' for MD and BE granular hydrogels (∼50-200 Pa). Void space was comparable across all groups, although EF granular hydrogels exhibited an increased number of pores and decreased average pore size when compared to MD and BE granular hydrogels. Furthermore, granular hydrogel properties were tuned by varying the amount of cross-linker used during microgel fabrication. Lastly, granular hydrogels were injectable across formulations due to their general shear-thinning and self-healing properties. Taken together, this work thoroughly characterizes the influence of the microgel fabrication technique on granular hydrogel properties to inform the design of future systems for biomedical applications.

摘要

传统上用于组织工程和药物输送的块状水凝胶有许多局限性,例如限制了可注射性和纳米级孔隙率,从而降低了细胞入侵和质量传递。解决这些局限性的一种不断发展的方法是制造水凝胶微球(即“微凝胶”),这些微球可以组装成颗粒状水凝胶。有许多制造微球的方法;然而,制造技术对颗粒状水凝胶性质的影响尚未得到探索。在这里,我们研究了三种微球制造技术(微流控装置(MD)、批量乳液(BE)和挤出机械破碎(EF))对所得颗粒状水凝胶性质(例如力学性能、孔隙率和可注射性)的影响。用各种反应性基团(即降冰片烯(NorHA)、戊烯酸酯(HA-PA)和甲基丙烯酸酯(MeHA))修饰的透明质酸(HA)用于形成平均直径约为 100 μm 的微球。MD 方法得到的是均匀的球形微球,BE 方法得到的是不均匀的球形微球,EF 方法得到的是不均匀的多边形微球。在各种反应性基团中,与 EF 方法相比,MD 和 BE 方法制造的微球的功能基团消耗较低。当微球被挤入颗粒状水凝胶中时,EF 颗粒状水凝胶的储能模量(')(约 1000-3000 Pa)始终比 MD 和 BE 颗粒状水凝胶的 G'(约 50-200 Pa)高一个数量级。所有组之间的空隙空间都相当,尽管 EF 颗粒状水凝胶与 MD 和 BE 颗粒状水凝胶相比,表现出更多的孔和更小的平均孔径。此外,通过改变微球制造过程中使用的交联剂的量来调节颗粒状水凝胶的性质。最后,由于颗粒状水凝胶具有普遍的剪切稀化和自修复特性,因此可以通过各种配方进行注射。总之,这项工作彻底描述了微球制造技术对颗粒状水凝胶性质的影响,为生物医学应用的未来系统设计提供了信息。

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