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Injectable and Tunable Gelatin Hydrogels Enhance Stem Cell Retention and Improve Cutaneous Wound Healing

机译:可注射和可调节的明胶水凝胶可增强干细胞保留能力并改善皮肤伤口愈合

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摘要

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.
机译:在临床前和临床试验中,干细胞已显示出对多种疾病的巨大希望。然而,低的细胞植入率显着限制了干细胞疗法的临床翻译。已经开发出许多可注射的水凝胶来增强细胞保留。然而,理想的材料具有可调节的特性,可以模仿不同的组织壁and并调节干细胞的行为,这仍然是一个未实现的承诺。在此,从多功能的基于PEG的超支化聚合物和可商购的硫醇化明胶中设计出具有高度可调性的可注射聚(乙二醇)(PEG)-明胶水凝胶。在生理条件下约2分钟内发生自发胶凝。鼠类脂肪干细胞(ASC)可以很容易地封装到水凝胶中,从而支持ASC的生长并保持其干性。通过改变水凝胶的配方和细胞接种密度,可以很好地控制水凝胶的机械性能,生物降解性和细胞反应。一项动物研究表明,使用鼠伤口愈合模型,原位形成的水凝胶可显着改善细胞保留能力,增强血管生成并加速伤口闭合。这些数据表明,可注射的PEG-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。

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  • 来源
    《Advanced Functional Materials》 |2017年第24期|1606619.1-1606619.12|共12页
  • 作者单位

    Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA|Univ Coll Dublin, Sch Med & Med Sci, Charles Inst Dermatol, Dublin 4, Ireland;

    Univ Coll Dublin, Sch Med & Med Sci, Charles Inst Dermatol, Dublin 4, Ireland;

    Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA;

    Univ Coll Dublin, Sch Med & Med Sci, Charles Inst Dermatol, Dublin 4, Ireland;

    Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA;

    Univ Coll Dublin, Sch Med & Med Sci, Charles Inst Dermatol, Dublin 4, Ireland;

    Univ Coll Dublin, Sch Med & Med Sci, Charles Inst Dermatol, Dublin 4, Ireland;

    Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    gelatin; hyperbranched polymers; injectable hydrogels; stem cells; wound healing;

    机译:明胶;超支化聚合物;可注射水凝胶;干细胞;伤口愈合;

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