Karim Najibulla, Golz Katrin, Bader Augustinus
TEPS-Tissue Engineering Platforms, Strasbourg, France.
Artif Organs. 2006 Oct;30(10):809-14. doi: 10.1111/j.1525-1594.2006.00304.x.
The shortage of human donor valves and disadvantages of current mechanical and xenogenic valve grafts cause a growing demand for biologically engineered valves. We developed a bioreactor for in vitro transformation of porcine semilunar heart valves into human valves. The reactor design was optimized in order to achieve a complete removal of porcine cells by trypsinization and cellularization of the remaining matrix with human vascular cells. The physical parameters of the reactor were characterized. Based on these data, decellularization and cellularization protocols were developed and the successful application of protocols was investigated by immunohistochemistry. The resulting reactor consisted of two connectable and perfuseable modules. Heart valve structures of varying sizes could be mounted into the reactor and could be completely depopulated within 4 days by a sequence of enzymatic and mechanical treatments applied simultaneously to the valves. Complete cellularization with human cells could be achieved after optimizing the seeding design, density, and time.
人类供体瓣膜的短缺以及当前机械瓣膜和异种瓣膜移植物的缺点导致对生物工程瓣膜的需求不断增长。我们开发了一种生物反应器，用于将猪半月形心脏瓣膜体外转化为人造瓣膜。对反应器设计进行了优化，以便通过胰蛋白酶消化完全去除猪细胞，并用人类血管细胞使剩余基质细胞化。对反应器的物理参数进行了表征。基于这些数据，制定了去细胞化和细胞化方案，并通过免疫组织化学研究了方案的成功应用。最终的反应器由两个可连接且可灌注的模块组成。不同尺寸的心脏瓣膜结构可安装到反应器中，并通过同时对瓣膜进行一系列酶促和机械处理，在4天内完全去除细胞。优化接种设计、密度和时间后，可实现用人类细胞完全细胞化。
