Design, realization and optimization of a disposable bioreactor
for culturing and testing heart valves
Citation for published version (APA):
Neerincx, P. E., Beelen, M. J., & Meijer, H. E. H. (2008). Design, realization and optimization of a disposable bioreactor for culturing and testing heart valves. Poster session presented at Mate Poster Award 2008 : 13th Annual Poster Contest.
Document status and date: Published: 01/01/2008 Document Version:
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Polymer Technology
Design, Realization and Optimization
of a Disposable Bioreactor for
Culturing and Testing Heart Valves
/department of mechanical engineering
P. E. Neerincx, M. J. Beelen, H. E. H. Meijer Den Dolech, Eindhoven
Introduction
The most common heart diseases include stenosis (improperly closing and opening of the aortic valve, see Figure (1)). In se-vere cases a heart valve replacement is needed. Nowadays this is done by using a mechanical valve or a tissue valve that are not able to grow and have a higher risk of thrombo-embolism. Tis-sue engineered heart valves, as shown in Figure (1), constructed of cells of the patient seeded on a scaffold and cultured in a bioreactor by mechanical conditioning, are a third alternative. Existing bioreactors have a large number of parts, either flow or strain applied and testing the heart valve is not possible. This results in the need for a new disposable bioreactor.
Figure 1: Human heart, heart valve stenosis (left) [1] and a tissue engineered heart valve (right) [2]
Objective
The goal of this research is to design and realize a disposable bioreactor, actuated by air pressure, for culturing and testing tissue engineered heart valves (by imitation of true physiological heart cycles) consisting of as few as possible parts that can be fabricated on the Ferromatic injection moulding machine in our laboratory.
Final design
Design steps and numerical simulations verified by rapid tool-ing resulted in a bioreactor design, as depicted in Figure (2), consisting of two identical shells that are fabricated by a two component (blue hard and red soft polymer) injection mould-ing process. Each shell is equipped with seals and air pressure actuated steering valves and membranes.
Figure 2: 3D Unigraphics model of the bioreactor (left) and a schematic representation of the active parts during heart cycle im-itation (right)
Two membranes (one for imitation of the left ventricle volume displacement and one for imitating the resistance, compliance of the blood vessels and the blood inertia in vivo) and one steering valve are needed to imitate the pressures in front of and behind the valve, the valve closing pressure and flow trough the valve,
see Figure (2). The other steering valves are needed during nu-trient fluid circulation and valve placing or removal.
Design realization
Figure (3) shows the mould used for injection moulding the biore-actor shells and a injection moulded biorebiore-actor assembly (con-sisting of shells, clips, pressure caps, tubes, connectors and a heart valve adapter) with air pressure actuated valves and mem-branes. Pressures measured in front of and behind the valve (in this case a hand made polyurethane valve) and the positions of the membranes (measured by ultrasonic sensors) and used for feedback control.
Figure 3: The bioreactor mould (left) and a bioreactor assembly (right)
Results
Figure (4) shows the results of the aortic and valve closing pres-sure imitation obtained using cycle volumes of 35 [cc] (80 [cc] in vivo) and therefore reduced maximum flows of 200 [cc/sec] (600 [cc/sec] in vivo). 0 0.5 1 1.5 2 −10 −5 0 5 10 15 20 time [sec] pressure [KPa]
imitation of aortic pressure
reference pressure measured pressure 0 0.5 1 1.5 2 −20 −15 −10 −5 0 5 10 15 20 25 time [sec] pressure [KPa]
imitation of the valve closing pressure reference pressure
measured valve closing pressure (Pao−Plv)
Figure 4: Imitation of the aortic pressure (left), and valve closing pressure (right)
Conclusions and Recommendations
A symmetrical, two component, mouldable and disposable biore-actor design is established with all functions for culturing and testing tissue engineered heart valves. A mould is designed and fabricated, bioreactor parts are injection moulded and used for a bioreactor assembly wherein physiological flows and pressures are successfully imitated, which can still be improved. A user friendly interface for an easy culture protocol implementation is needed, wherein pressure profiles and cycle volumes gradually increase in order to reach test values at the end.
References
[1] Human heart and stenosis: www.myhealth.com, Healthwise [2] Tissue engineered heart valve: biomedical brochure, TU/e
