动态席夫碱交联的壳聚糖基水凝胶的合成与性能研究

Synthesis and Property Documentation of Chitosan-Based Hydrogel Cross-Linked by Dynamic Schiff Base Bond

壳聚糖基水凝胶机械性能往往较差,为提高其机械性能通常进行戊二醛交联,但是戊二醛会对水凝胶的生物安全性造成影响。为在提高壳聚糖基水凝胶的机械性能时充分保障其生物安全性,本研究制备了一款完全基于壳聚糖及其衍生物的水凝胶。羧甲基壳聚糖(CMC)与双醛壳聚糖(DACS)通过席夫碱键共价交联,形成壳聚糖基水凝胶(CBH),通过流变学实验、拉伸实验、黏附实验对CBH的自愈合性能、机械性能进行评价。通过抗菌实验、活/死细胞实验、细胞毒性、溶血实验、抗炎实验对CBH的抗菌性能、生物相容性以及抗炎性能进行了全面评估。研究发现,CBH可拉伸至原长的2倍,在4 h后的愈合效率可达72%,这证明席夫碱键交联赋予了CBH良好的自愈合性能并提高了其机械性能。CBH的平衡溶胀率可达4 500%,且具有pH响应性。CBH对大肠杆菌(Escherichia coli)和金黄色葡萄球菌(Staphylococcus aureus)的抑制效率分别为80.95%和79.79%。与CBH共用培养的细胞可随时间正常增殖,无明显细胞死亡,且溶血率仅为3%,这证明CBH具有优异的生物相容性。同时,CBH还可以抑制一氧化氮和TNF-α、IL-1β、IL-6等促炎因子的分泌,增加IL-10等抗炎因子的分泌,具有良好的抗炎活性。研究结果表明,利用CMC和DACS制备的CBH,具有良好的自愈合性能、机械性能、抗菌、抗炎性能以及高度生物相容性,其在生物医学领域有广阔的应用潜力。

The mechanical performance of chitosan hydrogel is often undesirable,and glutaraldehyde cross-linking is widely carried out to improve their mechanical performance.Unfortunately,glutaraldehyde affects the biosafety of hydrogel.In order to improve the mechanical performance of chitosan hydrogel and ensure their biosafety,a hydrogel and its derivatives were prepared entirely from chitosan in this study.Carboxymethyl chitosan(CMC)and dialdehyde chitosan(DACS)were covalently crosslinked through Schiff base bonding to form a chitosan-based hydrogel(CBH).The self-healing and mechanical property of CBH were evaluated through rheological,tensile and adhesion experiments.In addition,the antibacterial function,biocompatibility and anti-inflammatory function of CBH were comprehensively evaluated via antibacterial,live/dead and anti-inflammatory assays,and cytotoxicity and haemolysis tests.It was found that CBH has a healing efficiency of 72%after 4 h and can be stretched to double its original length.Our results demonstrated that Schiff base bond cross-linking endows CBH with a good self-healing performance and improves its mechanical property.CBH has an equilibrium swelling rate of up to 4500%and is pH responsive.The inhibition efficiency against E.coli and S.aureus was 80.95%and 79.79%,respectively.Cells co-cultured with CBH proliferated normally over time without a significant cell death,and the hemolysis rate was only 3%,proving that CBH has an excellent biocompatibility.Meanwhile,CBH also inhibited the secretion of pro-inflammatory factors such as nitric oxide and TNF-α,IL-1β,IL-6,and increased the secretion of anti-inflammatory factors such as IL-10.Our results showed that CBH prepared by CMC and DACS have good self-healing,mechanical,antibacterial and anti-inflammatory properties,and are highly biocompatible.CBH holds broad potentials for being applied in biomedical fields.