Injectable and Tunable Gelatin Hydrogels Enhance Stem Cell Retention and Improve Cutaneous Wound Healing
Injectable and Tunable Gelatin Hydrogels Enhance Stem Cell Retention and Improve Cutaneous Wound Healing
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DOI：
10.1002/adfm.201606619
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发表时间：
2017-06-27
影响因子：
19
通讯作者：
Gurtner, Geoffrey C.
中科院分区：
文献类型：
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作者：
Dong, Yixiao;Sigen, A.;Gurtner, Geoffrey C.
在临床前和临床试验中，干细胞已经显示出对各种疾病的巨大希望。然而，较低的细胞植入率大大限制了干细胞疗法的临床应用。许多可注射的水凝胶已经被开发出来以增强细胞的保留力。然而，设计一种理想的材料，具有可调的性能，可以模拟不同的组织生态位，并调节干细胞的行为，仍然是一个未兑现的承诺。在这里，由多功能聚乙二醇基超支化聚合物和商业上可获得的硫醇化明胶设计了一种具有高度可调性能的可注射聚乙二醇明胶水凝胶。在生理条件下，自发凝胶化发生在大约2分钟内。小鼠脂肪干细胞(ASCs)可以很容易地被包裹到水凝胶中，支持ASC的生长并保持其干细胞的干性。通过改变水凝胶配方和细胞接种密度，可以很好地控制水凝胶的力学性能、生物降解性和细胞响应。一项动物研究表明，在小鼠伤口愈合模型中，原位形成的水凝胶显著改善了细胞保留率，增强了血管生成，并加速了伤口的愈合。这些数据表明，可注射的聚乙二醇明胶水凝胶可用于调节3D培养中的干细胞行为，为伤口愈合和其他组织再生应用输送细胞。
Stem cells have shown substantial promise for various diseases in preclinical and clinical trials. However, low cell engraftment rates significantly limit the clinical translation of stem cell therapeutics. Numerous injectable hydrogels have been developed to enhance cell retention. Yet, the design of an ideal material with tunable properties that can mimic different tissue niches and regulate stem cell behaviors remains an unfulfilled promise. Here, an injectable poly(ethylene glycol) (PEG)-gelatin hydrogel is designed with highly tunable properties, from a multifunctional PEG-based hyperbranched polymer and a commercially available thiolated gelatin. Spontaneous gelation occurs within about 2 min under the physiological condition. Murine adipose-derived stem cells (ASCs) can be easily encapsulated into the hydrogel, which supports ASC growth and maintains their stemness. The hydrogel mechanical properties, biodegradability, and cellular responses can be finely controlled by changing hydrogel formulation and cell seeding densities. An animal study shows that the in situ formed hydrogel significantly improves cell retention, enhances angiogenesis, and accelerates wound closure using a murine wound healing model. These data suggest that injectable PEG-gelatin hydrogel can be used for regulating stem cell behaviors in 3D culture, delivering cells for wound healing and other tissue regeneration applications.