Yao Ya, Wang Peilei, Li Xing, Xu Yang, Lu Gonggong, Jiang Qing, Sun Yong, Fan Yujiang, Zhang Xingdong
Biomaterials Building, National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, Sichuan 610064, PR China.
Biomaterials Building, National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, Sichuan 610064, PR China.
Acta Biomater. 2020 Jul 15;111:197-207. doi: 10.1016/j.actbio.2020.05.007. Epub 2020 May 17.
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.
可注射水凝胶因其临床操作便捷、手术无创以及能无缝填充不规则缺损而受到越来越多的关注。在此，可注射的双自交联HSMSSA水凝胶分别通过快速硫醇/马来酰亚胺点击化学反应和硫醇氧化反应形成，作为一级和二级自交联网络。分子量和前体浓度显著影响水凝胶的物理化学性质和生物学功能。尽管单一的HSMSSA凝胶（0.1兆道尔顿，10毫克/毫升）具有适度的可注射性、较好的机械性能以及体外软骨细胞良好的增殖能力，并且能在体内极大地促进软骨组织形成，但由于缺乏粘附位点，在维持新生细胞簇之间的有效连接方面难以维系。然而，通过将可注射的HSMSSA与生物活性I型胶原相结合形成的仿生可注射双自交联混合水凝胶，具有更好的抗降解性、软骨细胞粘附和增殖能力，特别是与透明软骨形成和聚蛋白聚糖分泌相关的多个基因表达水平有所提升，这可能是一种通过联合扩增的自体软骨细胞构建可注射软骨修复填充剂的潜在临床治疗策略。重要意义声明：一种可注射的基于透明质酸的双自交联水凝胶分别通过快速硫醇/马来酰亚胺点击化学反应和硫醇氧化反应形成，作为一级/二级自交联网络。分子量和前体浓度显著影响水凝胶的物理化学性质和生物学功能。尽管这种HSMSSA凝胶（0.1兆道尔顿，10毫克/毫升）具有适度的可注射性、较好的机械性能以及体外软骨细胞良好的增殖能力，并且能在体内极大地促进软骨组织形成，但由于缺乏粘附位点，导致新生细胞簇之间的连接无效。通过将可注射的HSMSSA与生物活性I型胶原相结合形成的仿生可注射双自交联混合水凝胶，改善了软骨细胞的粘附和增殖，特别是与透明软骨形成和聚蛋白聚糖分泌相关的多个基因表达水平有所提升。
