Vascular Composite Graft : Entwicklung einer kleinlumigen Gefäßprothese auf der Basis einer Fibringelmatrix ; Optimierung von Gussverfahren, Bioreaktor und Kulturbedingungen

摘要

Atherosclerosis remains the main cause of mortality in the western hemisphere despite remarkable advances in medicine. Though a prosthetic replacement of the diseased vessels is feasible, the long-term outcome depends on the type of prosthesis that is used, especially in small-calibered vessels. The patency rates of autologous vessels are significantly higher than those of vascular substitutes. However the availability of suitable vein or artery tissue is limited. Cardiovascular tissue engineering has emerged as an opportunity to produce small-caliber vascular grafts using autologous materials. Jockenhoevel et al. developed the Vascular Composite Graft to assure short-term availability of a vascular graft while minimizing the use of foreign material. This concerns a small-caliber vascular graft based on fibrin gel and autologous myofibroblasts, supported by a textile structure of PVDF. The matter of this dissertation is the improvement of the production process of Vascular Composite Graft, firstly described by Röhl. The new moulding process of the vascular graft faciliates an all-over polymerisation of the fibrin gel inside the mould and allows the equal distribution of cells upon the textile structure as condition precedent to its complete integration into the vascular wall. The main improvements of the existing bioreactor are: 1. The opportunity of integrating the mould as a flow chamber into the bioreactor system itself and 2. the fusion of the formerly separated circulations for applying physical forces and for providing stable culture conditions on the other. As a condition for a serial production serveral Vascular Composite Grafts can be produced at the same time. Furthermore the new bioreactor makes the cultivation of the vascular grafts under standardized conditions possible. This permits the production of Vascular Composite Grafts in a simple and reproducible way. The evaluation of suitable culture conditions for Vascular Composite Graft indicated a flow rate of 100 ml/min and a successively increasing mean pressure up to 100 mmHg as ideal parameters for physical stimulation. These results emphasize the importance of an adaptation of the physical stress applicated to cultured tissue to its state of development. In the future, increasing flow rates will have to be examined with regard to tissue development.