Novel Sensor-EnabledEx VivoBioreactor: A New Approach towards Physiological Parameters and Porcine Artery Viability

Abstract

The aim of the present work is to design and construct an ex vivo bioreactor system to assess the real time viability of vascular tissue. Porcine carotid artery as a model tissue was used in the ex vivo bioreactor setup to monitor its viability under physiological conditions such as oxygen, pressure, temperature, and flow. The real time tissue viability was evaluated by monitoring tissue metabolism through a fluorescent indicator “resorufin.” Our ex vivo bioreactor allows real time monitoring of tissue responses along with physiological conditions. These ex vivo parameters were vital in determining the tissue viability in sensor-enabled bioreactor and our initial investigations suggest that, porcine tissue viability is considerably affected by high shear forces and low oxygen levels. Histological evaluations with hematoxylin and eosin and Masson's trichrome staining show intact endothelium with fresh porcine tissue whereas tissues after incubation in ex vivo bioreactor studies indicate denuded endothelium supporting the viability results from real time measurements. Hence, this novel viability sensor-enabled ex vivo bioreactor acts as model to mimic in vivo system and record vascular responses to biopharmaceutical molecules and biomedical devices.

Artificial Circulatory Model for Analysis of Human and Artificial Vessels

“…Similar considerations have been taken into account by Mundagi et al, who investigated carotid arteries with lengths varying from 8 to 12 cm [2], whereas Piola et al mounted 5 cm long segments in the vessel culture system [14]. Contrary to our assumption, Miyakawa et al introduced saphenous veins with 2 cm each [16].…”

“…However, effects of altered flow conditions have only been investigated in human saphenous veins after coronary artery bypass grafting [13]. Mundagi et al also reported on an ex vivo bioreactor that allowed an evaluation of cellular interactions in the carotid artery of pigs under controlled physiologic conditions [2]. Oxygen saturation and temperature have been successfully controlled.…”

“…Piola et al applied an axial flow pump under a steady state regime achieving an unrealistic blood flow character [14]. On the contrary, Mundargi et al reconstructed the blood flow with the use of a peristaltic pump working at a constant speed, which did not reflect the human situation [2].…”

“…Therefore, both in vivo and ex vivo research is performed to find new strategies to protect the circulatory system [2]. However, in vivo experiments, performed mainly in animal models, may not directly reflect the changes in the human body, while clinical studies could raise ethical issues.…”

“…So far, few efforts have been taken to exploit the potential of ex vivo vessel bioreactors towards a high-fidelity ex vivo replication of the hemodynamic factors affecting arterial wall behavior in an artificial environment. Ex vivo vessel culture systems for replication of the hemodynamic factors enable investigation of flow and pressure conditions [2,14]. They may also offer the possibility to indicate the effects caused by wall shear stress [15,16], as well as generated by the pure pulsatile pressure [17,18].…”