Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Biotech. & Biomed. Reserch Institute, Northwest University, Taibai North Road 229, Xi'an 710069, Shaanxi, China.
Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Biotech. & Biomed. Reserch Institute, Northwest University, Taibai North Road 229, Xi'an 710069, Shaanxi, China.
Int J Biol Macromol. 2019 Dec 1;141:700-712. doi: 10.1016/j.ijbiomac.2019.08.233. Epub 2019 Aug 29.
In this study, we fabricated multifunctionalized hydrogel scaffolds based on hyaluronic acid (HA)-tyrosine and human-like collagen (HLC) by crosslinking with 1, 4-butanedioldiglycidyl ether (BDDE) for soft tissue fillers. The physicochemical of HA-tyrosine/BDDE (HTB) and various proportions of HA-tyrosine/BDDE/HLC (HTBH) hydrogels were characterized by swelling ratio, mechanical strength, morphology and thermal stability. The results demonstrated various HTBH hydrogels had superior performance in mechanical properties than HTB hydrogels. The biodegradation in vitro results demonstrated the degradation of HTBH hydrogels were slower than HTB hydrogels, and residual masses of HTBH hydrogels varied with different proportions of HA-tyrosine and HLC in the presence of the combination of HAse/collagenase I. The cell counting kit-8 (CCK-8), Hoechst/PI staining and cell adhesion of various HTBH hydrogels showed less cytotoxic and superior fibroblast attachment than those of HTB hydrogels. Moreover, subcutaneous injections of HTBH hydrogels containing high proportions of HLC in mice and rabbits all exhibit better biocompatibility and anti-biodegradation compared to HTB hydrogels after 1, 4, 8, 12 and 16 weeks. Hematoxylin-eosin staining (H&E), immunohistochemical and transmission electron microscope (TEM) analysis results indicated HTBH hydrogels had less intense inflammatory responses with increase proportion of HLC. Taken together, HTBH hydrogels had great potential application as ideal soft tissue fillers with excellent mechanical properties, biological stability and biocompatibility.
在这项研究中，我们通过用 1,4-丁二醇二缩水甘油醚（BDDE）交联，制备了基于透明质酸（HA）-酪氨酸和类人胶原蛋白（HLC）的多功能水凝胶支架，用于软组织填充剂。通过溶胀比、机械强度、形态和热稳定性对 HA-酪氨酸/BDDE（HTB）和不同比例的 HA-酪氨酸/BDDE/HLC（HTBH）水凝胶的物理化学性质进行了表征。结果表明，各种 HTBH 水凝胶在机械性能方面优于 HTB 水凝胶。体外降解结果表明，HTBH 水凝胶的降解速度比 HTB 水凝胶慢，在 HAse/胶原酶 I 的存在下，HTBH 水凝胶的残留质量随 HA-酪氨酸和 HLC 比例的不同而变化。细胞计数试剂盒-8（CCK-8）、Hoechst/PI 染色和各种 HTBH 水凝胶的细胞黏附实验表明，与 HTB 水凝胶相比，它们的细胞毒性更低，成纤维细胞黏附性更好。此外，在小鼠和兔体内皮下注射高比例 HLC 的 HTBH 水凝胶，与 HTB 水凝胶相比，在 1、4、8、12 和 16 周后，均表现出更好的生物相容性和抗降解性。苏木精-伊红染色（H&E）、免疫组织化学和透射电子显微镜（TEM）分析结果表明，随着 HLC 比例的增加，HTBH 水凝胶的炎症反应较弱。综上所述，HTBH 水凝胶具有良好的机械性能、生物稳定性和生物相容性，有望成为理想的软组织填充剂。
