Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Biomed Mater Res A. 2020 Dec;108(12):2504-2518. doi: 10.1002/jbm.a.37001. Epub 2020 Jun 20.
Polysaccharides are explored for various tissue engineering applications due to their inherent cytocompatibility and ability to form bulk hydrogels. However, bulk hydrogels offer poor control over their microarchitecture and multiscale hierarchy, parameters important to recreate extracellular matrix-mimetic microenvironment. Here, we developed a versatile platform technology to self-assemble oppositely charged polysaccharides into multiscale fibrous hydrogels with controlled anisotropic microarchitecture. We employed polyionic complexation through microfluidic flow of positively charged polysaccharide, chitosan, along with one of the three negatively charged polysaccharides: alginate, gellan gum, and kappa carrageenan. These hydrogels were composed of microscale fibers, which in turn were made of submicron fibrils confirming multiscale hierarchy. Fibrous hydrogels showed strong tensile mechanical properties, which were further modulated by encapsulation of shape-specific antioxidant cerium oxide nanoparticles (CNPs). Specifically, hydrogels with chitosan and gellan gum showed more than eight times higher tensile strength compared to the other two pairs. Incorporation of sphere-shaped cerium oxide nanoparticles in chitosan and gellan gum further reinforced fibrous hydrogels and increased their tensile strength by 40%. Altogether, our automated hydrogel fabrication platform allows fabrication of bioinspired biomaterials with scope for one-step encapsulation of small molecules and nanoparticles without chemical modification or use of chemical crosslinkers.
多糖因其固有细胞相容性和形成块状水凝胶的能力而被探索用于各种组织工程应用。然而，块状水凝胶对其微观结构和多尺度层次结构的控制较差，这些参数对于重建类似细胞外基质的微环境很重要。在这里，我们开发了一种通用的平台技术，通过带正电荷的多糖壳聚糖的微流控流动，将带相反电荷的多糖自组装成具有可控各向异性微观结构的多尺度纤维水凝胶。这些水凝胶由微尺度纤维组成，而这些纤维又由亚微米原纤维组成，从而证实了多尺度层次结构。纤维水凝胶具有很强的拉伸力学性能，通过封装特定形状的抗氧化铈氧化物纳米颗粒（CNP）进一步调节了其拉伸性能。具体来说，与其他两种配对物相比，壳聚糖和结冷胶组成的水凝胶的拉伸强度提高了 8 倍以上。将球形氧化铈纳米颗粒掺入壳聚糖和结冷胶中，进一步增强了纤维水凝胶的强度，并使其拉伸强度提高了 40%。总之，我们的自动化水凝胶制造平台允许制造具有仿生特性的生物材料，具有一步封装小分子和纳米颗粒的范围，而无需化学修饰或使用化学交联剂。
