School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
Mater Sci Eng C Mater Biol Appl. 2017 Feb 1;71:67-74. doi: 10.1016/j.msec.2016.09.068. Epub 2016 Sep 30.
Injectable hydrogels and microspheres derived from natural polysaccharides have been extensively investigated as drug delivery systems and cell scaffolds. In this study, we report a preparation of covalent hydrogels basing polysaccharides via the Schiff' base reaction. Water soluble carboxymethyl chitosan (CMC) and oxidized chondroitin sulfate (OCS) were prepared for cross-linking of hydrogels. The mechanism of cross-linking is attributed to the Schiff' base reaction between amino and aldehyde groups of polysaccharides. Furthermore, bovine serum albumin (BSA) loaded chitosan-based microspheres (CMs) with a diameter of 3.8-61.6μm were fabricated by an emulsion cross-linking method, followed by embedding into CMC-OCS hydrogels to produce a composite CMs/gel scaffold. In the current work, gelation rate, morphology, mechanical properties, swelling ratio, in vitro degradation and BSA release of the CMs/gel scaffolds were examined. The results show that mechanical and bioactive properties of gel scaffolds can be significantly improved by embedding CMs. The solid CMs can serve as a filler to toughen the soft CMC-OCS hydrogels. Compressive modulus of composite gel scaffolds containing 20mg/ml of microspheres was 13KPa, which was higher than the control hydrogel without CMs. Cumulative release of BSA during 2weeks from CMs embedded hydrogel was 30%, which was significantly lower than those of CMs and hydrogels. Moreover, the composite CMs/gel scaffolds exhibited lower swelling ratio and slower degradation rate than the control hydrogel without CMs. The potential of the composite hydrogel as an injectable scaffold was demonstrated by encapsulation of bovine articular chondrocytes in vitro. These results demonstrate the potential of CMs embedded CMC-OCS hydrogels as an injectable drug and cell delivery system in cartilage tissue engineering.
基于多糖的可注射水凝胶和微球已被广泛研究作为药物传递系统和细胞支架。在这项研究中,我们报告了一种通过席夫碱反应制备多糖共价水凝胶的方法。制备了水溶性羧甲基壳聚糖(CMC)和氧化硫酸软骨素(OCS)用于水凝胶的交联。交联的机制归因于多糖的氨基和醛基之间的席夫碱反应。此外,通过乳液交联法制备了直径为 3.8-61.6μm 的载牛血清白蛋白(BSA)壳聚糖基微球(CMs),然后将其嵌入 CMC-OCS 水凝胶中以制备复合 CMs/凝胶支架。在目前的工作中,研究了 CMs/凝胶支架的凝胶速率、形态、力学性能、溶胀比、体外降解和 BSA 释放。结果表明,通过嵌入 CMs 可以显著改善凝胶支架的力学和生物活性性能。固态 CMs 可以作为填充剂来增强软质 CMC-OCS 水凝胶的韧性。含有 20mg/ml 微球的复合凝胶支架的压缩模量为 13kPa,高于不含 CMs 的对照水凝胶。从嵌入微球的水凝胶中在 2 周内释放的 BSA 累积量为 30%,明显低于 CMs 和水凝胶。此外,与不含 CMs 的对照水凝胶相比,复合 CMs/凝胶支架具有更低的溶胀率和更慢的降解率。体外包封牛关节软骨细胞证明了复合水凝胶作为可注射支架的潜力。这些结果表明,嵌入 CMC-OCS 水凝胶的 CMs 作为软骨组织工程中可注射药物和细胞递送系统具有潜力。