Crosslinked nanogel-based porous hydrogel as a functional scaffold for tongue muscle regeneration

Crosslinked nanogel-based porous hydrogel as a functional scaffold for tongue muscle regeneration
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DOI:
10.1080/09205063.2020.1744246
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发表时间:
2020-06-15
影响因子:
3.6
通讯作者:
Akiyoshi, Kazunari
Akiyoshi, Kazunari
中科院分区:
工程技术4区
文献类型:
--
作者:
Kinoshita, Naoya;Sasaki, Yoshihiro;Akiyoshi, Kazunari

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舌癌的手术切除会损害语言和吞咽,降低生活质量。需要能够再生舌肌组织缺损的生物材料。理想情况下,这种生物材料将允许治疗性蛋白质的受控释放,支持治疗性细胞的存活和分化,并促进体内舌肌再生。本研究的目的是评估丙烯酰基修饰的交联纳米凝胶中的这些因素,该纳米凝胶由含胆固醇的普鲁兰多糖水凝胶纳米颗粒组成,以确定其作为舌切除术后再生治疗的潜力。水凝胶表现出相当大的孔隙率,并经历缓慢的生物降解。当装载模型蛋白质时,凝胶能够在血清中持续释放蛋白质超过两周,而没有初始的爆发释放。小鼠成肌细胞表现出对水凝胶的粘附,并且观察到细胞存活长达一周。凝胶包裹的成肌细胞表现出正常的肌管分化。将成肌细胞负载的凝胶植入小鼠的舌缺损中,并且在凝胶植入动物中新再生的肌纤维显著增加。开发的生物材料平台显示出作为舌切除术后再生治疗的巨大潜力,因为它有助于蛋白质和细胞介导的治疗,并刺激体内舌肌再生。
Surgical resection in tongue cancer can impair speech and swallowing, reducing quality of life. There is a need for biomaterials that can regenerate tongue muscle tissue defects. Ideally, such a biomaterial would allow controlled release of therapeutic proteins, support the survival and differentiation of therapeutic cells, and promote tongue muscle regenerationin vivo. The aim of the current study was to assess these factors in an acryloyl group-modified crosslinked nanogel, consisting of cholesterol-bearing pullulan hydrogel nanoparticles, to determine its potential as a regenerative therapeutic following tongue resection. The hydrogel demonstrated substantial porosity and underwent slow biodegradation. When loaded with a model protein, the gel enabled sustained protein release over two weeks in serum, with no initial burst release. Mouse myoblasts demonstrated adhesion to the hydrogel and cell survival was observed up to one week. Gel-encapsulated myoblasts demonstrated normal myotube differentiation. Myoblast-loaded gels were implanted in a tongue defect in mice, and there was a significant increase in newly-regenerated myofibers in gel-implanted animals. The developed biomaterial platform demonstrates significant potential as a regenerative treatment following tongue resection, as it facilitates both protein and cell-mediated therapy, and stimulates tongue muscle regenerationin vivo.