Extracellular matrix-inspired hydrogel of hyaluronan and gelatin crosslinked via a Link module with a transglutaminase reactive sequence
Extracellular matrix-inspired hydrogel of hyaluronan and gelatin crosslinked via a Link module with a transglutaminase reactive sequence
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DOI：
10.1038/s43246-022-00309-4
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发表时间：
2022-10-30
影响因子：
7.8
通讯作者：
Ito，Taichi
中科院分区：
文献类型：
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作者：
Okawa，Masashi;Tanabe，Aki;Ito，Taichi
细胞外基质（ECM）是体内细胞的天然支架。它具有复杂的结构，包括各种蛋白质，例如胶原蛋白和透明质酸（HA）等多糖。在这里，受到交联ECM结构的启发，我们设计了一个基因工程连接模块LinkCFQ-通过融合微生物转氨酶（MTG）反应标签的连接模块，HA结合域的肿瘤坏死因子刺激基因-6。尽管Link模块的HA特异性结合特性得以保留，但LinkCFQ显示出与各种蛋白质的优异MTG反应性。此外，ECM激发的水凝胶由HA-明胶混合物制成，该混合物通过HA/Link模块相互作用和LinkCFQ中MTG催化的异肽键形成而交联。细胞培养和小鼠实验证实了水凝胶的生物相容性和可降解性。我们的研究结果为组织工程、再生医学、药物发现和递送、疾病模型、生物织物和医疗器械的生物材料和蛋白质的设计提供了见解。
The extracellular matrix (ECM) is a natural scaffold of cells in the body. It has a complex structure comprising various proteins, such as collagen and hyaladherins, and polysaccharides such as hyaluronan (HA). Here, inspired by the crosslinked ECM structure, we design a genetically engineered Link module—LinkCFQ—by fusing a microbial transglutaminase (MTG)-reactive tag to the Link module, an HA-binding domain of tumor necrosis factor-stimulated gene-6. Although the HA-specific binding property of the Link module is preserved, LinkCFQ demonstrates excellent MTG reactivity with various proteins. Furthermore, an ECM-inspired hydrogel is fabricated from an HA–gelatin mixture crosslinked via HA/Link module interaction and MTG-catalyzed isopeptide bond formation in LinkCFQ. Cell culture and mouse experiments confirm the hydrogel’s biocompatibility and degradability. Our findings provide insights into the design of biomaterials and proteins for tissue engineering, regenerative medicine, drug discovery and delivery, disease models, biofabrication, and medical devices.