Center of 3D Printing & Organ Manufacturing, School of Fundamental Sciences, China Medical University (CMU), No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.
Molecules. 2020 Feb 10;25(3):756. doi: 10.3390/molecules25030756.
Crosslinking is an effective way to improve the physiochemical and biochemical properties of hydrogels. In this study, we describe an interpenetrating polymer network (IPN) of alginate/gelatin hydrogels (i.e., A-G-IPN) in which cells can be encapsulated for in vitro three-dimensional (3D) cultures and organ bioprinting. A double crosslinking model, i.e., using Ca to crosslink alginate molecules and transglutaminase (TG) to crosslink gelatin molecules, is exploited to improve the physiochemical, such as water holding capacity, hardness and structural integrity, and biochemical properties, such as cytocompatibility, of the alginate/gelatin hydrogels. For the sake of convenience, the individual ionic (i.e., only treatment with Ca) or enzymatic (i.e., only treatment with TG) crosslinked alginate/gelatin hydrogels are referred as alginate-semi-IPN (i.e., A-semi-IPN) or gelatin-semi-IPN (i.e., G-semi-IPN), respectively. Tunable physiochemical and biochemical properties of the hydrogels have been obtained by changing the crosslinking sequences and polymer concentrations. Cytocompatibilities of the obtained hydrogels are evaluated through in vitro 3D cell cultures and bioprinting. The double crosslinked A-G-IPN hydrogel is a promising candidate for a wide range of biomedical applications, including bioartificial organ manufacturing, high-throughput drug screening, and pathological mechanism analyses.
交联是改善水凝胶的物理化学和生物化学性质的有效方法。在本研究中，我们描述了一种藻酸盐/明胶水凝胶（即 A-G-IPN）的互穿聚合物网络（IPN），其中可以封装细胞用于体外三维（3D）培养和器官生物打印。利用双重交联模型，即使用 Ca 交联藻酸盐分子和转谷氨酰胺酶（TG）交联明胶分子，来改善藻酸盐/明胶水凝胶的物理化学性质，如保水能力、硬度和结构完整性，以及生物化学性质，如细胞相容性。为了方便起见，将单独离子（即仅用 Ca 处理）或酶（即仅用 TG 处理）交联的藻酸盐/明胶水凝胶分别称为藻酸盐半互穿网络（即 A-半互穿网络）或明胶半互穿网络（即 G-半互穿网络）。通过改变交联序列和聚合物浓度，可以获得可调的物理化学和生物化学性质的水凝胶。通过体外 3D 细胞培养和生物打印来评估所得水凝胶的细胞相容性。双交联 A-G-IPN 水凝胶是一种很有前途的候选材料，可用于广泛的生物医学应用，包括生物人工器官制造、高通量药物筛选和病理机制分析。
