Sreerekha Perumcherry Raman, Krishnan Lissy K
Thrombosis Research Unit, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.
Artif Organs. 2006 Apr;30(4):242-9. doi: 10.1111/j.1525-1594.2006.00211.x.
Completely biological tissue-engineered vascular graft is an upcoming substitute for damaged blood vessel, but its clinical use is currently limited due to poor mechanical strength. Therefore, at present, polymeric small-diameter vascular grafts lined with endothelial cells (ECs) to reduce graft thrombosis may be a more viable option. Successful construction of EC-seeded artificial grafts faces some challenges such as (i) retention of endothelial lining; and (ii) availability of differentiated autologous cells. Biomaterial surfaces that are modified by depositing extracellular matrix (ECM) components may stabilize cells in the lumen against forces of blood flow. Adult stem cells such as endothelial progenitor cells (EPCs) circulate in the blood and they usually attach to the exposed matrix at the injured blood vessel site. Depending on the signaling capabilities of ECM, cells may differentiate into ECs,, and if a similar composition of the matrix is provided in vitro, EPCs isolated from blood might get differentiated and thus autologous cells for tissue engineering may be obtained. In this in vitro study, ECM scaffold consisting of biomolecules such as fibrin, fibronectin, and gelatin along with growth factors is found to have supported differentiation of EPC into EC. Further, the ECM precoated on Dacron and polytetrafluoroethylene is found to have supported the formation of EC monolayer that synthesized nitric oxide, and resisted shear stress. Thus, biomimetic fibrin composite is found to be suitable not only to seed cells on currently available artificial grafts but also to obtain differentiated EC from EPC.
完全生物组织工程血管移植物是一种即将用于替代受损血管的材料,但由于其机械强度较差,目前在临床上的应用受到限制。因此,目前,内衬内皮细胞(ECs)以减少移植物血栓形成的聚合物小直径血管移植物可能是一个更可行的选择。成功构建接种内皮细胞的人工移植物面临一些挑战,例如:(i)内皮衬里的保留;以及(ii)分化的自体细胞的可用性。通过沉积细胞外基质(ECM)成分进行修饰的生物材料表面可以使管腔内的细胞抵抗血流的作用力而保持稳定。成体干细胞,如内皮祖细胞(EPCs),在血液中循环,它们通常附着在受损血管部位暴露的基质上。根据ECM的信号传导能力,细胞可能分化为内皮细胞,并且如果在体外提供类似的基质成分,从血液中分离的EPCs可能会分化,从而获得用于组织工程的自体细胞。在这项体外研究中,发现由纤维蛋白、纤连蛋白和明胶等生物分子以及生长因子组成的ECM支架支持EPC分化为内皮细胞。此外,发现预涂覆在涤纶和聚四氟乙烯上的ECM支持合成一氧化氮并抵抗剪切应力的内皮细胞单层的形成。因此,发现仿生纤维蛋白复合材料不仅适用于在现有的人造移植物上接种细胞,而且适用于从EPC获得分化的内皮细胞。