小口径人工血管的原位再生及炎症反应的作用

Small diameter artificial vascular grafts（SDAVG) have great clinical needs. In situ regeneration and reconstruction of SDAVG is a straightforward and effective method which is a greatly complex process involving in the body and used biomaterials. The mechanical and degradable properties of biomaterials and the architectural structure of the SDAVG play very important influence on vascular regeneration in situ. Based on our our previous research results,this project put forward: the preparation of biocompatible polyester biomaterials with different degradation rates and mechanical properties,which will be used to fabricate new types of fiber-based SDAVG using fiber weaving technology,melt and solution electrospinning technologies, the resulting SDAVG is expected to be capable of regenerating and remodeling vascular intima, tunica media and tunica adventitia in situ. The effects of the SDAVG mechanical properties, degradation rates, pore size and porosity, as well as diameter and orientation of fiber on patency, endothelialization and formation of smooth muscle layer will be investigated through the abdomen aorta transplantation in SD rats. The intimal hyperplasia, calcification and regeneration of capillary and the new neural network will also be studied by long-term inplantation(1-2 years). Moreover, the effects of inflammatory response and macrophages on the regeneration of vascular tissue will be researched. With optimizing material properties and conditions for the preparation of vascular grafts, new small diameter vessels with similar structure to natural blood vessels would be regenerate in situ. This study holds important clinical value for in situ regeneration of SDAVG using of cell-free grafts.

小口径人工血管具有巨大的临床需求，其原位再生与重建是直接而有效地方法。小口径人工血管原位再生与重建是宿主和材料共同参与的复杂过程。针对材料的降解速度、力学性质和人工血管的结构对血管原位再生的影响。基于我们的前期研究结果，本项目提出：合成不同降解速度和力学性质的生物相容性聚酯生物材料，采用纤维编织、熔融电纺丝和溶液电纺丝等技术制备新型的能够再生血管内膜、中膜和外膜的纤维基小口径人工血管，通过大鼠腹主动脉移植实验研究材料的降解速度、力学性质及纤维基人工血管的孔径大小、孔隙率、纤维直径及取向程度对于通畅性、内皮化和平滑肌层再生的影响规律与调控机制。远期考察新内膜发生/发展、钙化现象、毛细血管新生及神经网络形成。探索炎症反应程度和巨噬细胞对人工血管组织再生的影响。在体内实现拟天然血管结构的血管再生与重建。本项目对于无细胞人工血管的原位再生具有重要的理论意义和使用价值

小口径人工血管具有巨大的临床需求，其原位再生与重建是直接而有效的方法。小口径人工血管原位再生与重建是宿主和材料共同参与的复杂过程。本项目研究并证明了白藜芦醇和神经肽物质能够通过促进内皮化和平滑肌细胞再生，调控巨噬细胞的表型和分布来促进PCL人工血管的血管再生。利用材料结构诱导/引导组织再生的原理，通过设计制备了纤维取向或孔道取向的人工血管移植物，通过控制结构和降解来促进血管组织重塑以及支架的力学性能，阐释了巨噬细胞的招募和极化对血管再生的影响，为具有诱导动脉再生能力的移植物的制备提供了一种新的策略。证实了负载TanⅡA的取向微米纤维支架通过调节巨噬细胞表型转变促进内源性干细胞募集和血管化，同时抑制了纤维包裹，增加了支架内部的细胞外基质沉积，此类材料可作为一种极具应用潜力的新型生物材料来促进例如肌肉，肌腱，神经等取向组织的内源性修复