Xu Sheng, Li Qingtao, Pan Haotian, Dai Qiyuan, Feng Qi, Yu Chenxi, Zhang Xiaohua, Liang Zhibin, Dong Hua, Cao Xiaodong
Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, People's Republic of China.
National Engineering Research Center for Tissue Restoration and Reconstruction (NERC-TRR), South China University of Technology, Guangzhou 510641, People's Republic of China.
ACS Biomater Sci Eng. 2020 Dec 14;6(12):6896-6905. doi: 10.1021/acsbiomaterials.0c01183. Epub 2020 Nov 19.
In recent years, biomimetic tubular scaffolds have been widely used to repair various human tissue defects, due to their hollow structure similar to the native tissues such as blood vessel, trachea, ureter, and bone marrow cavity. However, there are still many challenges in manufacturing a tubular hydrogel scaffold with suitable mechanical properties, specific microstructure, and good biocompatibility. In this study, we exploited an enzymatic cross-linking method using horseradish peroxidase (HRP) as an enzyme and hydrogen peroxide (HO) as a substrate, and combining with gelatin's thermal sensitivity to produce an enzymatically cross-linked silk fibroin/gelatin-tyramine (E-SF/GT) tubular hydrogel. Through further treatment with methanol, we fabricated an EM-SF/GT tubular hydrogel with fine-wall architecture that consists of two different layers (inner and outer, dense and porous). Mechanical measurement showed that the compressive moduli values were up to 4.82 MPa and the tensile moduli values were up to 4.79 kPa under the static loading conditions. Also, degradation test showed that the hydrogel's degradation time was prolonged. Finally, the bioactivity was tested by seeding mouse bone marrow mesenchymal stem cells (mBMSCs) in the lumen of a small-diameter (2 mm) EM-SF/GT tubular hydrogel. Cell morphology and immunofluorescence test indicated that mBMSCs differentiated into endothelial cells and lined the inner surface of the tubular hydrogel under induction. This work provided a feasible strategy for developing tubular hydrogels, which could be potentially used as scaffolds for hollow multilayer tissue engineering, such as blood vessels.
近年来，仿生管状支架因其空心结构与血管、气管、输尿管和骨髓腔等天然组织相似，已被广泛用于修复各种人体组织缺损。然而，制造具有合适机械性能、特定微观结构和良好生物相容性的管状水凝胶支架仍面临许多挑战。在本研究中，我们利用以辣根过氧化物酶（HRP）为酶、过氧化氢（HO）为底物的酶交联方法，并结合明胶的热敏性，制备了一种酶交联丝素蛋白/明胶-酪胺（E-SF/GT）管状水凝胶。通过甲醇进一步处理，我们制备了一种具有精细壁结构的EM-SF/GT管状水凝胶，它由两层不同的层（内层和外层，致密层和多孔层）组成。力学测量表明，在静态加载条件下，压缩模量值高达4.82 MPa，拉伸模量值高达4.79 kPa。此外，降解试验表明水凝胶的降解时间延长。最后，通过将小鼠骨髓间充质干细胞（mBMSCs）接种到小直径（2 mm）EM-SF/GT管状水凝胶的管腔中来测试其生物活性。细胞形态和免疫荧光测试表明，mBMSCs在诱导下分化为内皮细胞并排列在管状水凝胶的内表面。这项工作为开发管状水凝胶提供了一种可行的策略，其有可能用作中空多层组织工程的支架，如血管。
