小口径同轴共纺血管支架构建过程参数对其生物学特性的影响规律

According to the problems of easier blood coagulation and thrombus, lower long-term patency rate and poor mechanical strength after small diameter vascular scaffolds were implanted in vivo, we put forward to construct sequential multilayer blood vessels using coaxial electrospinning technique with good biocompatible human-like collagen, and improve the biological properties of vascular scaffolds by construction process and culture methods. It will be studied to fluid properties of the electrospinning solution and fluid dynamics of coaxial electrospinning process, vascular scaffold surface morphologies, spatial structure, hydrophilicity, hydrophobicity, charge, surface energy and mechanical properties, and through the correlation analysis between which and biocompatibility, we will reveal constraints and rules for coaxial electrospinning process control engineering. Training methods and means of cultivation will be developed in order to improve the vascular scaffold mechanical strength, then we can obtain the perfusion rate of growth kinetics, substrate consumption dynamics and deposition kinetics of ectosecretion matrix. By the study, we can master the intrinsic relationship between mechanical strength and structure, composition and blood compatibility, cell compatibility of construction, and which can provide a theoretical basis for further improving mechanical properties and biocompatibility of vascular tissue engineering scaffold.

针对小口径血管支架植入体内后易凝血、易形成血栓、远期通畅率低、力学强度差等现象，课题组提出用良好生物相容性的类人胶原蛋白作为基本材料，以静电纺丝同轴共纺技术获得顺序多层血管支架及体外培养方式两方面为切入点，提高所构建组织工程血管支架的生物学性能。通过研究预纺丝溶液的流体性质及同轴共纺过程中流体动力学与所形成血管支架的表面形貌、空间结构、亲疏水性、荷电性、表面能、力学性能及生物相容性的相关性，揭示同轴共纺过程中的工程控制限制因素及规律。研究可以提高血管支架的力学强度的培养方式、培养手段，获得灌注速率下的生长动力学、培养基质消耗动力学和胞外分泌的基质沉积动力学。真正掌握支架的结构、组成与组织相容性、细胞相容性及机械强度之间的内在关系。为进一步提高小口径血管支架的力学性能及生物相容性提供理论依据。

心脑血管疾病严重危害着人类的健康。临床替代手术中，大口径(＞6mm)人工血管对高流量、低阻力的血管替代效果较好，但小口径(＜4-6mm)人工血管，由于生物相容性、力学强度差、易出现血栓等原因一直困扰着临床医生。针对这一现象，本课题提出采用生物相容性好的类人胶原蛋白为基本材料，通过优化同轴共纺顺序多层血管支架的静电纺丝工艺条件和体外培养方式，提高血管支架的力学性能。并对其理化性能及生物学相容性进行评估。结果表明：(1)当HLC/chitosan/PEO=4/3/1时，获得以类人胶原蛋白和壳聚糖为复合纺丝纤维的血管内层；当HLC/silk fibroin/PEO=3/2/1时，获得以类人胶原蛋白丝素蛋白纺丝纤维的中间层；当PLA/(H+C+P)=1/4，获得以类人胶原蛋白聚乳酸壳聚糖作为血管外层的顺序多层支架。(2) SEM结果显示，纤维直径大部分分布在为694 nm，与天然血管纤维接近。(3) 血管支架动态培养后，最大应力从4.0 MPa提高到4.5MPa，应变从20%提高到25%。(4) 该复合多层血管支架能够有效促进细胞贴附与增殖，组织相容性良好。本研究将为小口径血管支架的进一步研究提供经验及理论支持。