Development of the biodegradable graft for cardiovascular surgery with function of local release of growth factors and cytokines

目的：为克服目前合成人工血管的缺点，研制了可生物降解的心血管外科人工血管。最近，骨髓细胞（BMCs）已被接种到移植物再生自体血管壁。然而，一些生长因子和血管生成细胞因子，如碱性成纤维细胞生长因子（bFGF），尚未用于血管壁的再生。在本研究中，我们试图开发一种新的可生物降解的合成移植物释放bFGF在体内，并调查了局部释放的bFGF结合BMC播种的疗效，用于创建血管壁组织下的低压系统，如肺动脉或腔静脉。方法：可生物降解的补丁被用来修复透壁缺损手术造成的右心室流出道的成年大鼠心脏。在植入后2周和4周进行组织学评估。结果：植入后2周，补片的内皮细胞表面发生内皮化。与标准移植物相比，明胶混合移植物中植入bFGF的移植物的新血管形成突出。在明胶混合移植物中，BMC接种促进了新血管形成，bFGF与BMC接种结合的给药进一步增强了新血管形成。bFGF的管理加速了弹性蛋白的积累4 weeks postplantation.Conclusions：明胶混合的可降解的移植物导致局部释放的bFGF，和管理bFGF结合BMC种植是有效的，促进移植物中的新生血管。这种组织工程血管移植物可能是一种有前途的心血管外科材料，可以导致自体静脉壁组织的再生。

Objective: Biodegradable grafts for cardiovascular surgery have been developed to overcome shortcomings of current nonbiodegradable synthetic grafts. Recently, bone marrow cells (BMCs) have been seeded into the graft to regenerate the autologous vascular wall. However, some growth factors and angiogenic cytokines, such as basic fibroblast growth factor (bFGF), have not been used in regeneration of the vascular wall. In the present study, we tried to develop a new biodegradable synthetic graft to release bFGF in vivo, and investigated the efficacy of local release of bFGF combined with BMC seeding for creating vascular wall tissue under low-pressure systems such as the pulmonary artery or vena cava.Methods: Biodegradable patches were used to repair transmural defects created surgically in the right ventricular outflow tract of adult rat hearts. Histologic assessments were performed at 2 and 4 weeks after implantation.Results: Endothelialization on the endocardial surface of the patch occurred 2 weeks after implantation. Neovascularization of the implanted graft impregnated with bFGF was prominent in the gelatin-blended graft compared with the standard graft. In the gelatin-blended graft, BMC seeding promoted neovascularization, and administration of bFGF combined with BMC seeding further enhanced neovascularization. Administration of bFGF accelerated the elastin accumulation 4 weeks after implantation.Conclusions: The gelatin-blended biodegradable graft led to local release of bFGF, and administration of bFGF combined with BMC seeding was effective in promoting neovascularization in the graft. This tissue-engineered vascular graft may be a promising material for cardiovascular surgery that could lead to the regeneration of autologous venous wall tissue.