Dual Crosslinked Gelatin Methacryloyl Hydrogels for Photolithography and 3D Printing
Dual Crosslinked Gelatin Methacryloyl Hydrogels for Photolithography and 3D Printing
复制标题
DOI：
10.3390/gels5030034
复制
发表时间：
2019-09-01
期刊：
影响因子：
4.6
通讯作者：
Zorlutuna, Pinar
中科院分区：
文献类型：
--
作者：
Basara, Gozde;Yue, Xiaoshan;Zorlutuna, Pinar
明胶甲基丙烯酰基(GelMA)水凝胶具有良好的生物相容性、光敏性、印刷性以及可调的力学和流变性，已广泛应用于组织工程和再生医学领域。然而，较低的机械强度限制了它们在药物控制释放、非病毒基因治疗以及组织和疾病建模方面的应用。在这项工作中，介绍了一种凝胶MA的双重交联法。首先，使用光刻技术通过甲基丙烯酸甲酯与明胶MA的胺基进行交联制得凝胶图案。其次，引入了微生物谷氨酰胺转氨酶(MTGase)溶液，通过引发GelMA水凝胶中谷氨酰胺和赖氨酸基团之间的化学反应，酶促交联光敏凝胶。结果表明，与紫外线照射或mTGase处理的单交联剂相比，双交联剂改善了水凝胶的硬度和流变性，而不影响细胞存活率。我们的结果还表明，当用mTGase处理时，水凝胶显示出较低的溶胀性能和更好的光刻图案形状保存。当用mTGase处理三维(3D)打印和光交联的底物时，也观察到类似的效果。这种双重交联法可用于改善GelMA凝胶的力学性能和图案保真度，以及动态控制组织工程构造的硬度。
Gelatin methacryloyl (GelMA) hydrogels have been used in tissue engineering and regenerative medicine because of their biocompatibility, photopatternability, printability, and tunable mechanical and rheological properties. However, low mechanical strength limits their applications in controlled drug release, non-viral gene therapy, and tissue and disease modeling. In this work, a dual crosslinking method for GelMA is introduced. First, photolithography was used to pattern the gels through the crosslinking of methacrylate incorporated amine groups of GelMA. Second, a microbial transglutaminase (mTGase) solution was introduced in order to enzymatically crosslink the photopatterned gels by initiating a chemical reaction between the glutamine and lysine groups of the GelMA hydrogel. The results showed that dual crosslinking improved the stiffness and rheological properties of the hydrogels without affecting cell viability, when compared to single crosslinking with either ultraviolet (UV) exposure or mTGase treatment. Our results also demonstrate that when treated with mTGase, hydrogels show decreased swelling properties and better preservation of photolithographically patterned shapes. Similar effects were observed when three dimensional (3D) printed and photocrosslinked substrates were treated with mTGase. Such dual crosslinking methods can be used to improve the mechanical properties and pattern fidelity of GelMA gels, as well as dynamic control of the stiffness of tissue engineered constructs.