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Bioreactor for Dynamic Flexural Stimulation

Background

Dynamic flexure is a major mode of deformation in the native heart valve cusp, and may effect the mechanical and biological development of tissue engineered heart valves (TEHV). This novel bioreactor was developed to study the effect of dynamic flexural stimulation on TEHV biomaterials. It has been implemented in a study to compare the effect of uni-directional cyclic flexure on the effective stiffness of two candidate TEHV scaffolds: a non-woven mesh of polyglycolic acid (PGA) .bers, and a non-woven mesh of PGA and poly l-lactic acid (PLLA) fibers, both coated with poly 4-hydroxybutyrate (P4HB).

Device Operation

The bioreactor consists of two identical chambers (127mm_101.6 mm),

Bioreactor for Dynamic Flexural Stimulation
Bioreactor operating inside a standard cell culture incubator at 37_C and 5% CO2. The bioreactor consists of two parallel chambers secured to a base plate and coupled via a cross-arm to a centrally positioned linear actuator.

each containing 6 culture wells (25.4mm diameter, 16mm deep). Situated within each well are four stainless-steel ‘‘stationary posts’’ arranged orthogonally around a central channel in the floor of the culture well. The device can accommodate a total of 12 rectangular samples (maximum dimensions approximately 25mm_7.5mm_2 mm), with each sample being positioned between the four stationary posts, orthogonal to the central channel. The structural elements of the device were machined from polysulfone, chosen for its excellent thermal and chemical stability, and abrasion-resistant acrylic, which provides good optical transparency.

Dynamic flexural stimulation can be applied to each of the samples in the form of cyclic three-point flexure by an environmentally sealed linear actuator. The piston of the actuator is rigidly coupled to a cross arm in the form of a T-junction. Conversely, the cross-arm is rigidly coupled to the arm of each chamber. Each arm bifurcates and extends into a chamber (two penetrations per chamber). Both arms terminate in six fingers through which ‘‘flexure pins’’ can be inserted to bracket the rectangular samples in the middle. Therefore, each sample can be subjected to uni-directional or bi-directional three-point flexure. Frequency, amplitude, acceleration, and deceleration profiles can be developed using Windows-based Si Programmer software (Applied Motion Products, Watsonville, CA). The structural elements of the device can be cold gas sterilized by ethylene oxide, and the entire device was designed to be operated inside of a standard humidified incubator.

For more information, please see the following article:

[1] Engelmayr, G.C., Hildebrand, D.K., Sutherland, F.W.H., Mayer, J.E., Sacks, M.S. A novel bioreactor for the dynamic flexural stimulation of tissue engineered heart valve biomaterials. Biomaterials 24 (2003) 2523–2532

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