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A di-self-crosslinking hyaluronan-based hydrogel combined with type I collagen to construct a biomimetic injectable cartilage-filling scaffold.
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-05-17 , DOI: 10.1016/j.actbio.2020.05.007
Ya Yao 1 , Peilei Wang 1 , Xing Li 1 , Yang Xu 1 , Gonggong Lu 1 , Qing Jiang 1 , Yong Sun 1 , Yujiang Fan 1 , Xingdong Zhang 1
Affiliation  

Injectable hydrogels have attracted increasing attention because of convenient clinical operation, non-invasive surgical procedure and seamless filling of irregular defects. Here, injectable di-self-crosslinking HSMSSA hydrogel was formed via fast thiol/maleimide click chemistry reaction and thiol oxidation reaction as primary and secondary self-crosslinking network, respectively. Molecular weight and precursor concentration significantly affected physichemical properties and biological functions of hydrogels. Although single HSMSSA gel (0.1 M Da, 10 mg/mL) had moderate injectability, preferable mechanical properties and good proliferative ability of chondrocytes in vitro, and could greatly promote cartilaginous tissue formation in vivo, the lack of adhesion sites resulted in an untenable situation in maintaining effective connections among newborn cell clusters. However, the biomimetic injectable di-self-crosslinking blend hydrogel by combing injectable HSMSSA and bioactive Col I had improved resistance to degradation, chondrocytes adhesion and proliferation, especially for multiples ascending genes expression level associated with hyaline cartilage formation and polyproteoglycan secretion, which might be a potential clinical treatment strategy for constructing injectable cartilage repair filler by combining expanded autologous chondrocytes.

Statement of Significance

An injectable di-self-crosslinking Hyaluronan–Based hydrogel was formed via fast thiol/maleimide click chemistry reaction and thiol oxidation reaction as primary/secondary self-crosslinking network, respectively. Molecular weight and precursor concentration significantly affected physichemical properties and biological functions of the hydrogels. Although this HSMSSA gel (0.1 M Da, 10 mg/mL) had moderate injectability, preferable mechanical properties, and good proliferative ability of chondrocytes in vitro, and could greatly promote cartilaginous tissue formation in vivo, the lack of adhesion sites resulted in ineffective connections among newborn cell clusters. The biomimetic injectable di-self-crosslinking blend hydrogel improved chondrocyte adhesion and proliferation by combined injectable HSMSSA and bioactive Col I, especially for multiple ascending gene expression levels associated with hyaline cartilage formation and polyproteoglycan secretion.



中文翻译:

一种基于二自我交联的透明质酸的水凝胶,结合I型胶原蛋白,可构建仿生的可注射软骨填充支架。

由于方便的临床操作,无创外科手术程序和不规则缺陷的无缝填充,可注射水凝胶引起了越来越多的关注。在此,通过快速硫醇/马来酰亚胺点击化学反应和硫醇氧化反应分别作为一级和二级自交联网络,形成了可注射的双自交联HSMSSA水凝胶。分子量和前体浓度显着影响水凝胶的理化性质和生物学功能。尽管单个HSMSSA凝胶(0.1 M Da,10 mg / mL)具有中等注射能力,但其体外软骨细胞具有较好的力学性能和良好的增殖能力,并且可以大大促进体内软骨组织的形成,缺乏粘附位点导致维持新生细胞簇之间有效连接的不可持续的情况。但是,将可注射的HSMSSA和生物活性Col I组合在一起可仿生的可注射的双自交联共混水凝胶具有更好的抗降解,软骨细胞黏附和增殖的能力,特别是对于与透明软骨形成和多蛋白聚糖分泌相关的多个上升基因表达水平。通过结合扩展的自体软骨细胞构建可注射的软骨修复填充剂的潜在临床治疗策略。

重要声明

通过快速硫醇/马来酰亚胺点击化学反应和硫醇氧化反应分别作为一级/二级自交联网络形成了可注射的双自交联透明质酸基水凝胶。分子量和前体浓度显着影响水凝胶的理化性质和生物学功能。尽管该HSMSSA凝胶(0.1 M Da,10 mg / mL)具有适度的注射性,较好的机械性能以及体外软骨细胞的良好增殖能力,并且可以大大促进体内软骨组织的形成,缺乏粘附位点导致新生细胞簇之间的无效连接。仿生可注射双自交联混合水凝胶通过可注射HSMSSA和生物活性Col I的结合改善了软骨细胞的粘附和增殖,特别是与透明软骨形成和多蛋白聚糖分泌相关的多个上升基因表达水平。

更新日期:2020-06-24
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