Robert H Smith Institute of Plant Science and Genetics, Robert H Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, Rehovot, Israel.
Division of Medicinal Chemistry, Israel Institute for Biological Research, Ness-Ziona, Israel.
J Tissue Eng Regen Med. 2022 Feb;16(2):140-150. doi: 10.1002/term.3265. Epub 2021 Nov 22.
Polyvinyl alcohol (PVA)-based hydrogels are promising biomaterials for tissue engineering printing applications. However, one of their main disadvantages is their inability to support cell attachment, which is a critical feature for the preparation of biological scaffolds. The goal of this study was to develop a printable, cell-supportive PVA-based bioink with tunable mechanical properties, without using animal-derived polymers which potentially harbor human pathogens. An ultraviolet light (UV) curable PVA-methacrylate (PVA-MA) polymer mixed with Cys-Arg-Gly-Asp (CRGD) peptide was developed. This peptide holds the integrin receptor binding sequence - RGD, that can enhance cell attachment. The additional cysteine was designed to enable its thiol binding under UV to methacrylate groups of the UV curable PVA-MA. Vero cell, as an adherent cell model was used to assess the hydrogel's cell adhesion. It was found that the PVA-MA-CRGD formula enables the preparation of hydrogels with excellent cell attachment and had even shown superior cell attachment properties relative to added gelatin. Adding hyaluronic acid (HA) as a rheologic modulator enabled the printing of this new formula. Our overall data demonstrates the applicability of this mixture as a bioink for soft tissue engineering such as skin, adipose, liver or kidney tissue.
聚乙烯醇(PVA)基水凝胶是组织工程打印应用中很有前途的生物材料。然而,其主要缺点之一是无法支持细胞附着,这是制备生物支架的关键特征。本研究的目的是开发一种可打印的、具有可调节机械性能的细胞支持性 PVA 基生物墨水,而不使用可能携带人类病原体的动物源性聚合物。本研究开发了一种可紫外光(UV)固化的 PVA-甲基丙烯酰胺(PVA-MA)聚合物,与含有整合素受体结合序列-RGD 的半胱氨酸-精氨酸-甘氨酸-天冬氨酸(CRGD)肽混合。该肽含有整合素受体结合序列-RGD,可增强细胞附着。额外的半胱氨酸设计用于在 UV 下将其巯基与 UV 可固化的 PVA-MA 的甲基丙烯酰基结合。作为贴壁细胞模型的vero 细胞用于评估水凝胶的细胞粘附性。结果发现,PVA-MA-CRGD 配方可制备具有优异细胞附着性的水凝胶,甚至显示出比添加明胶更好的细胞附着性能。添加透明质酸(HA)作为流变改性剂可使这种新配方得以打印。我们的整体数据表明,这种混合物可作为软组织工程(如皮肤、脂肪、肝脏或肾脏组织)的生物墨水使用。