颗粒水凝胶支架(GHS)是通过将水凝胶微粒(HMP)紧密接触(包装),然后是物理和/或化学颗粒间键的形成。明胶甲基丙烯酰(GelMA)GHS最近已成为生物医学应用的有希望的平台;然而,很少有人知道如何包装积木,物理交联的软GelMAHMP,影响GHS的物理(孔微结构和机械/流变特性)和生物学(体外和体内)属性。这里,GHS孔微体系结构是通过外部(离心)力诱导的填料和GelMAHMP变形来调节GHS机械和流变特性,以及体外和体内的生物反应。增加离心力的大小和持续时间会增加HMP变形/填料,降低GHS空隙率和中值孔径,并增加GHS压缩和存储模量。MDA-MB-231人三阴性乳腺癌细胞在松散堆积的GHS中在GelMAHMP表面扩散并变平,而由于空间限制,它们在高度堆积的GHS中采用细长的形态。通过在GHS中培养未处理或blebistatin处理的细胞,显示了非肌肉肌球蛋白II驱动的收缩性对细胞形态的影响。在小鼠体内皮下植入证实了显著较高的内皮细胞,成纤维细胞,和巨噬细胞浸润在GHS内,具有较低的填充密度,这与体外细胞迁移结果一致。这些结果表明,GelMAGHS的包装状态可以实现体外细胞反应和体内组织反应的工程化。这项研究是标准化和工程化GelMAGHS微体系结构以进行组织工程和再生的基本一步。
Granular hydrogel scaffolds (GHS) are fabricated via placing hydrogel microparticles (HMP) in close contact (packing), followed by physical and/or chemical interparticle bond formation. Gelatin methacryloyl (
GelMA) GHS have recently emerged as a promising platform for biomedical applications; however, little is known about how the packing of building blocks, physically crosslinked soft
GelMA HMP, affects the physical (pore microarchitecture and mechanical/rheological properties) and biological (in vitro and in vivo) attributes of GHS. Here, the GHS pore microarchitecture is engineered via the external (centrifugal) force-induced packing and deformation of GelMA HMP to regulate GHS mechanical and rheological properties, as well as biological responses in vitro and in vivo. Increasing the magnitude and duration of centrifugal force increases the HMP deformation/packing, decreases GHS void fraction and median pore diameter, and increases GHS compressive and storage moduli. MDA-MB-231 human triple negative breast adenocarcinoma cells spread and flatten on the
GelMA HMP surface in loosely packed GHS, whereas they adopt an elongated morphology in highly packed GHS as a result of spatial confinement. Via culturing untreated or blebbistatin-treated cells in GHS, the effect of non-muscle myosin II-driven contractility on cell morphology is shown. In vivo subcutaneous implantation in mice confirms a significantly higher endothelial, fibroblast, and macrophage cell infiltration within the GHS with a lower packing density, which is in accordance with the in vitro cell migration outcome. These results indicate that the packing state of
GelMA GHS may enable the engineering of cell response in vitro and tissue response in vivo. This research is a fundamental step forward in standardizing and engineering
GelMA GHS microarchitecture for tissue engineering and regeneration.