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首页> 外文期刊>Advanced Functional Materials >Bio-Orthogonally Crosslinked, Engineered Protein Hydrogels with Tunable Mechanics and Biochemistry for Cell Encapsulation
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Bio-Orthogonally Crosslinked, Engineered Protein Hydrogels with Tunable Mechanics and Biochemistry for Cell Encapsulation

机译：生物正交交联的工程蛋白水凝胶，具有可调的力学和生物化学特性，可用于细胞包封

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摘要

Covalently-crosslinked hydrogels are commonly used as 3D matrices for cell culture and transplantation. However, the crosslinking chemistries used to prepare these gels generally cross-react with functional groups present on the cell surface, potentially leading to cytotoxicity and other undesired effects. Bio-orthogonal chemistries have been developed that do not react with biologically relevant functional groups, thereby preventing these undesirable side reactions. However, previously developed biomaterials using these chemistries still possess less than ideal properties for cell encapsulation, such as slow gelation kinetics and limited tuning of matrix mechanics and biochemistry. Here, engineered elastin-like proteins (ELPs) are developed that crosslink via strain-promoted azide-alkyne cycloaddition (SPAAC) or Staudinger ligation. The SPAAC-crosslinked materials form gels within seconds and complete gelation within minutes. These hydrogels support the encapsulation and phenotypic maintenance of human mesenchymal stem cells, human umbilical vein endothelial cells, and murine neural progenitor cells. SPAAC-ELP gels exhibit independent tuning of stiffness and cell adhesion, with significantly improved cell viability and spreading observed in materials containing a fibronectin-derived arginine-glycine-aspartic acid (RGD) domain. The crosslinking chemistry used permits further material functionalization, even in the presence of cells and serum. These hydrogels are anticipated to be useful in a wide range of applications, including therapeutic cell delivery and bioprinting.
机译：共价交联的水凝胶通常用作细胞培养和移植的3D基质。然而，用于制备这些凝胶的交联化学通常与细胞表面上存在的官能团发生交叉反应，潜在地导致细胞毒性和其他不良作用。已经开发了不与生物学相关的官能团反应的生物正交化学，从而防止了这些不良副反应。然而，先前使用这些化学方法开发的生物材料仍具有较不理想的细胞封装特性，例如缓慢的凝胶动力学以及有限的基质力学和生物化学调节。在这里，工程弹性蛋白样蛋白（ELPs）被开发出来，可以通过应变促进的叠氮化物-炔烃环加成（SPAAC）或施陶丁格连接来交联。 SPAAC交联的材料在数秒内形成凝胶，并在数分钟内完全凝胶化。这些水凝胶支持人间充质干细胞，人脐静脉内皮细胞和鼠神经祖细胞的封装和表型维持。 SPAAC-ELP凝胶表现出独立的硬度和细胞粘附性调节，在含有纤连蛋白衍生的精氨酸-甘氨酸-天冬氨酸（RGD）域的材料中观察到，细胞活力和铺展性显着提高。所使用的交联化学试剂即使在存在细胞和血清的情况下也允许进一步的材料功能化。预期这些水凝胶可用于广泛的应用中，包括治疗性细胞递送和生物打印。

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