3D生物打印技术促进人工血管内皮化

Endothelialization is considered as one of the most promising methods to solve the problem of vascular restenosis after artificial vascular replacement. Efforts have been made to improve endothelialization of artificial vessels, but the result was not satisfactory. Microenvironment is the key factor affecting normal cell function. Studies have proved that cell distribution is an important factor affecting cell microenviroment. But due to technical restriction, current studies on vascular endothelialization have not focused on the role of cell distribution in vascular endothelialization. With the progression of 3D bio-printing technology, it is possible to realize the accurate artificial arrangement of cell distribution. In this project, by using molecular imaging and immunohistochemical method, the precise distribution of vascular cells will be obtained and vascular digital model will be constructed. Taking advantage of 3D bio-printing technology, cells will be precisely planted on artificial vessels which will be used to study the impact of cell distribution on endothelization of artificial vessels. The expected results of this project are: (1) to understand the precise distribution of vascular endothelial cells and smooth muscle cells in the vessel; (2) to determine the role of improved arrangement by 3D bio-printing technique of vascular endothelial cells in the artificial vascular endothelialization.

促进内皮化是解决人工血管置换术后血管发生再狭窄问题的关键。科研工作者为解决人工血管内皮化问题进行了大量研究尝试但效果都不理想。细胞微环境是影响细胞功能正常发挥的关键，已有研究证明细胞分布是影响细胞微环境的一个重要因素，但基于技术条件限制，目前对血管内皮化的研究都未涉及到细胞分布的问题。3D生物打印技术的日趋成熟，使实现人工调控细胞精确定位成为可能。本项目将通过分子影像、免疫组化等实验手段获得血管细胞分布的精确结构，构建血管数字模型，利用3D生物打印技术将细胞精确排布种植在人工血管上，研究“细胞分布对人工血管内皮化的影响”。本项目研究的预期结果是：1、明确血管中内皮细胞与平滑肌细胞的精确分布规律。2、验证细胞精确定位种植在促进人工血管内皮化方面的作用。本项目的完成，将从细胞分布这一新的角度对血管重塑的机制进行阐述，并为解决临床人工血管内皮化提供新的思路和方案。

本项目以恒河猴作为实验动物模型，将自体来源的脂肪间充质干细胞进行体外扩增培养并制备成生物墨汁，通过3D生物打印机构建3D生物打印血管，对恒河猴腹主动脉进行血管置换。术后进行临床观察、影像学检测和组织病理学检测。观察期包括急性期（24 小时内）、亚慢性期（术后5-70天）和慢性期（术后71天及以上）。实验结果显示，植入的3D生物打印血管不仅形成完整的内皮细胞层，还具有完整的与血管收缩功能密切相关的平滑肌细胞层，且与自体血管完美融合成一体。该技术成功制造出具有与自体血管结构和功能相一致的人工血管，是人工血管发展史上新的里程碑。