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首页> 外文期刊>Advanced Functional Materials >Covalently Adaptable Elastin-Like Protein-Hyaluronic Acid (ELP-HA) Hybrid Hydrogels with Secondary Thermoresponsive Crosslinking for Injectable Stem Cell Delivery
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Covalently Adaptable Elastin-Like Protein-Hyaluronic Acid (ELP-HA) Hybrid Hydrogels with Secondary Thermoresponsive Crosslinking for Injectable Stem Cell Delivery

机译：具有二次热响应性交联的共价适应性弹性蛋白样蛋白-透明质酸（ELP-HA）杂化水凝胶，用于可注射干细胞递送。

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摘要

Shear-thinning, self-healing hydrogels are promising vehicles for therapeutic cargo delivery due to their ability to be injected using minimally invasive surgical procedures. An injectable hydrogel using a novel combination of dynamic covalent crosslinking with thermoresponsive engineered proteins is presented. Ex situ at room temperature, rapid gelation occurs through dynamic covalent hydrazone bonds by simply mixing two components: hydrazine-modified elastin-like protein (ELP) and aldehyde-modified hyaluronic acid. This hydrogel provides significant mechanical protection to encapsulated human mesenchymal stem cells during syringe needle injection and rapidly recovers after injection to retain the cells homogeneously within a 3D environment. In situ, the ELP undergoes a thermal phase transition, as confirmed by coherent anti-Stokes Raman scattering microscopy observation of dense ELP thermal aggregates. The formation of the secondary network reinforces the hydrogel and results in a tenfold slower erosion rate compared to a control hydrogel without secondary thermal crosslinking. This improved structural integrity enables cell culture for three weeks postinjection, and encapsulated cells maintain their ability to differentiate into multiple lineages, including chondrogenic, adipogenic, and osteogenic cell types. Together, these data demonstrate the promising potential of ELP-HA hydrogels for injectable stem cell transplantation and tissue regeneration.
机译：剪切稀化，自修复水凝胶因其具有使用微创外科手术程序进行注射的能力，因此有望用于治疗性货物运输。提出了使用动态共价交联与热响应工程蛋白的新型组合的可注射水凝胶。在室温下非原地，通过简单地混合两个组分：肼修饰的弹性蛋白样蛋白（ELP）和醛修饰的透明质酸，通过动态的共价键发生快速胶凝。这种水凝胶在注射器针头注射过程中为封装的人间充质干细胞提供了显着的机械保护，并在注射后迅速恢复，以将细胞均匀地保留在3D环境中。如相干的反斯托克斯拉曼散射显微镜观察所致，致密的ELP热聚集体所证实的，ELP原位经历了热相变。与没有次级热交联的对照水凝胶相比，次级网络的形成增强了水凝胶并导致腐蚀速率慢了十倍。这种改进的结构完整性使细胞能够在注射后培养三周，并且封装的细胞保持了分化为多种谱系的能力，包括成软骨，成脂和成骨细胞类型。总之，这些数据证明了ELP-HA水凝胶在可注射干细胞移植和组织再生中的潜力。

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