取向微通道细胞外基质人工血管的构建与功能修饰诱导血管拟天然再生

At present, synthetic materials and decellularized extracellular matrix (dECM) are mainly used to construct small diameter vascular grafts. The structure of synthetic materials can be controlled by various techniques, but its compatibility is inferior to dECM, the compatibility of dECM is excellent, while its structure is uncontrollable, which will hinder the regeneration of dECM small diameter vascular grafts. In this study, we will employ orientated polymer microfiber scaffolds as pore-formed templates, the tubular tissue capsule were formed with the help of the host regenerative capacity after the templates were implanted subcutaneously in animals, and then the polymer microfibers leaching process and cell extraction were performed successively, so that the orientated microchannel extracellular matrix vascular grafts were obtained, which can simultaneously achieve the migration and orientated regeneration of vascular smooth muscle cell. To achieve the aim of the prevention of acute thrombosis and fast endothelialization, the coagulation factors (heparin or hirudin) and endothelialization promoting peptides (SDF-1α or REDV) were modified on the surface of vascular grafts through collagen mimetic peptide (CMP). Finally, the animal carotid artery transplantation model (rabbit or rat) were used to evaluate tissue regeneration of the vascular grafts. In order to acquire some vascular grafts owning clinical application prospects, the construction condition of vascular grafts would be optimized according to evaluation results.

当前，构建小口径人工血管主要包括合成材料和脱细胞基质两类，其中合成材料的结构可通过多种工艺来控制，但它的相容性稍差，脱细胞基质的相容性较好，但其结构致密，限制了这类人工血管的细胞迁移和再生。针对上述问题，我们将结合两种材料的优势，设计并构建结构可控的脱细胞基质人工血管，进而对其进行功能修饰，促进该人工血管的再生。本项目拟采用取向聚合物微米纤维支架作为模板，将其埋植于动物皮下，利用宿主再生能力形成管状组织包裹，脱掉聚合物纤维和细胞，获得能够引导平滑肌拟天然再生的取向微通道细胞外基质人工血管。基于细胞外基质材料富含胶原的特性，通过胶原模拟肽将抗凝因子（肝素或水蛭素）和促内皮化多肽（SDF-1α或REDV）修饰到人工血管表面以实现其抗凝血与快速内皮化的目的。通过人工血管大鼠（异体）和兔子（异种）颈动脉血管移植，根据其诱导血管组织再生的效果优化人工血管的性能，以获得具有临床应用前景的人工血管。

血管，神经，跟腱和肌肉等组织缺损的功能恢复一直临床上的难题。组织工程材料的发展为这些受损组织的修复提供了新的方向。模拟天然组织的结构特点来设计和构建组织修复材料被证明是一种有效的修复手段。基于此，我们设计了具有不同拟天然组织结构的多种材料来修复缺损组织。其中包括：1）取向微通道细胞外基质用于血管，神经，肌肉和跟腱缺损组织再生；2）取向PCL微米纤维人工血管大鼠腹主动脉移植长期评价；3）可降解弹性取向PLCL微米纤维双层人工血管促进血管组织重塑；4）构建内层光滑双层人工血管改善血液相容性和内皮形成；5）梯度孔结构丝素蛋白支架用于组织工程。我们发现这些材料均能在一定程度上恢复受损组织的功能，尤其是细胞外基质材料支架效果要优于聚合物材料。材料的降解对于血管组织功能的恢复具有促进作用。多孔细胞外基质材料相比天然组织脱细胞材料，能够显著增强内源性重塑能力和功能恢复。这些材料也具有较大的临床转化价值，这些研究为组织再生材料的设计提供了新思路和参考。