In the present study, we fabricated non-toxic, injectable, and thermo-sensitive NIPAAm-g-chitosan (NC) hydrogels with thiol modification for introduction of disulfide cross-linking strategy. Previously, NIPAAm and chitosan copolymer has been proven to have excellent biocompatibility, biodegradability and rapid phase transition after injection, suitable to serve as cell carriers or implanted scaffolds. However, weak mechanical properties significantly limit their potential for biomedical fields. In order to overcome this issue, we incorporated thiol side chains into chitosan by covalently conjugating N-acetyl-cysteine (NAC) with carbodiimide chemistry to strengthen mechanical properties. After oxidation of thiols into disulfide bonds, modified NC hydrogels did improve the compressive modulus over 9 folds (11.4 kPa). Oscillatory frequency sweep showed the positive correlation between storage modulus and cross-liking density as well. Additionally, there was no cytotoxicity observed to mesenchymal stem cells, fibroblasts and osteoblasts. We suggested that the thiol-modified thermo-sensitive polysaccharide hydrogels are promising to be a cell-laden biomaterial for tissue regeneration.

在本研究中，我们制造了无毒、可注射和热敏的 NIPAAm- g- 具有硫醇修饰的壳聚糖 (NC) 水凝胶，用于引入二硫键交联策略。此前，NIPAAm与壳聚糖共聚物已被证明具有优异的生物相容性、生物降解性和注射后的快速相变，适合作为细胞载体或植入支架。然而，较弱的机械性能显着限制了它们在生物医学领域的潜力。为了克服这个问题，我们通过将 N-乙酰半胱氨酸 (NAC) 与碳二亚胺化学共价结合来将硫醇侧链掺入壳聚糖中，以增强机械性能。在硫醇氧化成二硫键后，改性的 NC 水凝胶确实将压缩模量提高了 9 倍以上（11.4 kPa）。振荡频率扫描也显示储能模量与交联密度呈正相关。此外，没有观察到对间充质干细胞、成纤维细胞和成骨细胞的细胞毒性。我们建议硫醇修饰的热敏多糖水凝胶有望成为一种用于组织再生的载细胞生物材料。