论文题名(中文): | 海藻酸盐/聚丙烯酰胺-壳聚糖水凝胶及其用于硬脊膜修复的研究 |
姓名: | |
论文语种: | chi |
学位: | 硕士 |
学位类型: | 学术学位 |
学校: | 北京协和医学院 |
院系: | |
专业: | |
指导教师姓名: | |
论文完成日期: | 2023-05-10 |
论文题名(外文): | Alginate/Polyacrylamide-Chitosan Hydrogel and Its Application in Spinal Dural Repair |
关键词(中文): | |
关键词(外文): | spinal dura defect cerebrospinal fluid leakage spinal dura patch wet environment adhesive hydrogel |
论文文摘(中文): |
目的:硬脊膜缺损和脑脊液漏是脊柱手术常见的并发症。常用的缝合或密封剂的硬脊膜修补方式存在针眼漏或密封失败的风险。本研究拟研发一种湿环境自粘性补片,探讨其用于修复硬脊膜缺损的可能性及其生物学功能。 方法:以海藻酸钠、丙烯酰胺、壳聚糖作为主要原料,通过二次交联方法合成补片。在体外测试该材料的溶胀性能、抗拉伸性能、粘附性能、抗菌性能以及细胞相容性。并构建硬脊膜缺损修复模型,验证该材料的密封性能及其体内修复效果。 结果与讨论:0.25 M 钙离子二次交联处理后的补片基质有最佳的孔隙连通率、孔径和抗拉伸性能,断裂应变11.76±1.72倍,满足硬脊膜活动需求。补片的粘附性满足硬脊膜密封需求。体外抗菌实验证实补片杀菌率可超过99%,可有效预防术后感染。该补片的细胞相容性良好,早期促成纤维细胞增殖,可加速硬脊膜缺损的封闭过程。可承受压力为790 mmH2O,远超生理脑脊液的压力,且长期密封效果稳定。构建了硬脊膜缺损修复的大鼠动物模型,发现 GFAP、IBA-1和MBP在术后显著下调,提示该补片具备抗炎、镇痛和抗粘连作用。 结论:本研究将自粘补片的设计理念应用于硬脊膜缺损修复领域,研制的水凝胶补片具有紧密密封、抗炎、止痛和抗菌的优良特性,作为一种新型硬脊膜缺损修复材料具有良好的应用前景。同时,构建了多种硬脊膜修复效果评估的体内外模型,一定程度上解决了该领域研究中缺乏可靠模型的问题。 |
论文文摘(外文): |
Objective: Dural defects and cerebrospinal fluid leaks are common complications of spinal surgery. The commonly used dural repair with sutures or sealants has the risk of needle leakage or seal failure. In this study, we developed a new self-adhesive patch and investigated its potential use for repairing dural defects and its biological function. Methods: First, the patch was synthesized by a secondary cross-linking method using sodium alginate, acrylamide, and chitosan as the main matrix materials. The patch was tested in vitro for its swelling properties, tensile resistance, adhesion properties, antibacterial properties, and cytocompatibility. Then, fresh porcine small intestine and porcine dural membrane were used to construct a dural defect repair model to verify the sealing properties of the patch. Finally, a rat dural defect repair model was constructed, and the in vivo repair effect of patch was explored by tissue sections and immunohistochemical staining. Results and Discussion: The 0.25 M calcium ion secondary cross-linked treated matrix had the best pore connectivity, pore size and tensile resistance. The fracture strain is 11.76±1.72 times, the tensile stress is 20.28±4.34 kPa, and the Young's modulus is 2.56±0.01 kPa. The adhesion strength of adhesive layer met the spinal dural repair requirements and met the standards of medical tape. In vitro antimicrobial experiments confirmed that the inhibition ratio of the patch could exceed 99% and prevent postoperative infection occurring. Cellular tests have shown that the patch is cytocompatible and promotes fibroblast proliferation in the initial stage which can accelerate the closure process of dural defects. The patch can withstand pressures far beyond physiological pressure of cerebrospinal fluid and is stable for long-term sealing. Cytokines such as GFAP, IBA-1 and MBP, associated with inflammation, pain, and scar formation, were significantly downregulated at 1-3 weeks after surgery, enhancing the anti-inflammatory, analgesic, and anti-adhesive effects of the tissue surrounding the defect site. Conclusion: The hydrogel patch developed in this study has excellent properties of tight sealing, anti-inflammatory, analgesic and antibacterial properties, and has good prospects in application of a new dural defect repair material. |
开放日期: | 2023-06-15 |