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Synthesis and characterization of site selective photo-crosslinkable glycidyl methacrylate functionalized gelatin-based 3D hydrogel scaffold for liver tissue engineering
Biomaterials Advances ( IF 7.9 ) Pub Date : 2021-02-11 , DOI: 10.1016/j.msec.2020.111694
Md Moniruzzaman Sk , Prativa Das , Amit Panwar , Lay Poh Tan

The presented work outlined the development of a new biocompatible hydrogel material that has potential applications in soft tissue engineering. As a proof of concept, human hepatocytes were used to demonstrate the suitability of this material in providing conducive environment for cellular growth and functional development. Herein, a detailed synthesis of novel gelatin derivatives - photo-crosslinkable glycidyl methacrylate (GMA) functionalized gelatins (Gelatin-GMA), and preparation of three-dimensional (3D) hydrogel scaffolds for the encapsulated Huh-7.5 cells is reported. The Gelatin-GMA biopolymers were synthesized at two different pH values of 3.5 (acidic) and 10.5 (basic) where two different photo-crosslinkable polymers were formed utilizing –COOH & –OH groups in acidic pH, and –NH2 & –OH groups in basic pH. The hydrogels were prepared using an initiator (Irgacure I2959) in the presence of UV light. The Gelatin-GMA biopolymers were characterized using spectroscopic studies which confirmed the successful preparation of the polymer derivatives. Rheological measurement was carried out to characterize the mechanical properties and derive the mesh sizes of the 3D hydrogels. Subsequently, detailed in vitro hepatocyte compatibility and functionality studies were performed in the 3D cell seeded hydrogel platform. The 3D hydrogel design with larger mesh sizes utilizes the advantage of the excellent diffusion properties of porous platform, and enhanced cell-growth was observed, which in turn elicited favorable Huh-7.5 response. The hydrogels led to improved cellular functions such as differentiation, viability and proliferation. Overall, it showed that the Gelatin-GMA based hydrogels presented better results compared to control sample (GelMA) because of the higher mesh sizes in Gelatin-GMA based hydrogels. Additionally, the functional group studies of the two Gelatin-GMA samples revealed that the cell functionalities are almost unaffected even after the tripeptide - Arg-Gly-Asp (RGD) in Gelatin-GMA synthesized at pH 3.5 is no longer completely available.



中文翻译:

用于肝组织工程的定点选择性光交联的甲基丙烯酸缩水甘油酯功能化明胶基3D水凝胶支架的合成与表征

提出的工作概述了一种新的生物相容性水凝胶材料的开发,该材料在软组织工程中具有潜在的应用。作为概念的证明,人类肝细胞被用来证明这种材料在为细胞生长和功能发育提供有利环境方面的适用性。本文中,报道了新型明胶衍生物的详细合成-可光交联的甲基丙烯酸缩水甘油酯(GMA)功能化明胶(Gelatin-GMA),以及用于封装的Huh-7.5细胞的三维(3D)水凝胶支架的制备。明胶-GMA生物聚合物是在两种不同的pH值3.5(酸性)和10.5(碱性)下合成的,其中两种不同的光可交联聚合物是利用酸性pH的–COOH&–OH和–NH 2形成的。碱性pH中的-OH基团。在紫外光存在下,使用引发剂(Irgacure I2959)制备水凝胶。明胶-GMA生物聚合物的使用光谱学研究进行了表征,证实了聚合物衍生物的成功制备。进行流变学测量以表征机械性能并得出3D水凝胶的筛孔尺寸。随后,详细体外在3D细胞接种的水凝胶平台中进行了肝细胞相容性和功能性研究。具有较大筛孔尺寸的3D水凝胶设计利用了多孔平台优异的扩散特性的优势,并观察到增强的细胞生长,进而引发了良好的Huh-7.5反应。水凝胶导致改善的细胞功能,例如分化,生存力和增殖。总体而言,这表明基于明胶-GMA的水凝胶比对照样品(GelMA)表现出更好的结果,因为基于明胶-GMA的水凝胶的筛孔尺寸更大。此外,对两个明胶-GMA样品的官能团研究表明,即使在pH 3合成的明胶-GMA中的三肽-Arg-Gly-Asp(RGD)之后,细胞功能几乎也不受影响。

更新日期:2021-02-24
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