Compact and tunable stretch bioreactor advancing tissue engineering implementation. Application to engineered cardiac constructs

Physical stimuli are crucial for the structural and functional maturation of tissues both in vivo and in vitro. In tissue engineering applications, bioreactors have become fundamental and effective tools for providing biomimetic culture conditions that recapitulate the native physical stimuli. In addition, bioreactors play a key role in assuring strict control, automation, and standardization in the production process of cell-based products for future clinical application. In this study, a compact, easy-to-use, tunable stretch bioreactor is proposed. Based on customizable and low-cost technological solutions, the bioreactor was designed for providing tunable mechanical stretch for biomimetic dynamic culture of different engineered tissues. In-house validation tests demonstrated the accuracy and repeatability of the imposed mechanical stimulation. Proof of concepts biological tests performed on engineered cardiac constructs, based on decellularized human skin scaffolds seeded with human cardiac progenitor cells, confirmed the bioreactor Good Laboratory Practice compliance and ease of use, and the effectiveness of the delivered cyclic stretch stimulation on the cardiac construct maturation

An automated 3D-printed perfusion bioreactor combinable with pulsed electromagnetic field stimulators for bone tissue investigations

In bone tissue engineering research, bioreactors designed for replicating the main features of the complex native environment represent powerful investigation tools. Moreover, when equipped with automation, their use allows reducing user intervention and dependence, increasing reproducibility and the overall quality of the culture process. In this study, an automated uni-/bi-directional perfusion bioreactor combinable with pulsed electromagnetic field (PEMF) stimulation for culturing 3D bone tissue models is proposed. A user-friendly control unit automates the perfusion, minimizing the user dependency. Computational fluid dynamics simulations supported the culture chamber design and allowed the estimation of the shear stress values within the construct. Electromagnetic field simulations demonstrated that, in case of combination with a PEMF stimulator, the construct can be exposed to uniform magnetic fields. Preliminary biological tests on 3D bone tissue models showed that perfusion promotes the release of the early differentiation marker alkaline phosphatase. The histological analysis confirmed that perfusion favors cells to deposit more extracellular matrix (ECM) with respect to the static culture and revealed that bi-directional perfusion better promotes ECM deposition across the construct with respect to uni-directional perfusion. Lastly, the Real-time PCR results of 3D bone tissue models cultured under bi-directional perfusion without and with PEMF stimulation revealed that the only perfusion induced a similar to 40-fold up-regulation of the expression of the osteogenic gene collagen type I with respect to the static control, while a similar to 80-fold up-regulation was measured when perfusion was combined with PEMF stimulation, indicating a positive synergic proosteogenic effect of combined physical stimulations

AIM (Artery in microgravity): Design and development of an ice cubes mission

The Artery In Microgravity (AIM) project is the first experiment to be selected for the “Orbit Your Thesis!” programme of ESA Academy. It is a 2U experiment cube designed for the ICE Cubes facility on board of the International Space Station. The experiment is expected to be launched on SpaceX-20 in early 2020. The project is being developed by an international group of students from ISAE-SUPAERO and Politecnico di Torino, under the supervision of the ISAE-SUPAERO and Politecnico di Torino staff. The experiment is a test-bench for investigating haemodynamics in microgravity focusing on coronary heart disease, the most common form of cardiovascular disease and the cause of approximately 9 million deaths every year. Coronary heart disease is caused by stenosis of the coronary artery due to the build-up of plaque. While the development of atherosclerosis is not fully understood, the primary event seems to be subtle and repeated injury to the artery walls through various mechanisms including physical stresses from flow disturbances as well as from systemic and biological risk factors. In the presence of severe stenosis, patients are treated with the implantation of one or more coronary stents, which are tubular scaffolds devoted to restore and maintain myocardial perfusion. The coronary stenting procedure is largely applied (e.g., 1.8 million stents per year implanted in USA) In view of the impact that coronary artery disease has on humans, as well as of the increasing number of people that will be involved in space flights in the future, the way astronauts in space coronary hemodynamics is affected by the absence of gravity in the presence of stenosis or of stenting needs to be investigated in depth. In addition, as most stents are metallic objects, the radiation exposure in space might interact with their surface, altering blood flow, inducing particles release and ultimately leading to stent failure. Therefore, the aim of AIM is to start studying the vascular haemodynamics in a stented and a stenosed coronary artery on Earth and in microgravity and the stent-radiation coupling. This will allow to learn about the effect gravity plays on coronary artery haemodynamics, the effects of microgravity and radiation on the performance of implantable devices and ultimately the risks of myocardial infarction to astronauts on long-distance spaceflight. The experimental setup consists of a closed hydraulic loop containing two models of a coronary artery in series. An electric pump and reservoir will control the flow of a blood-mimicking fluid through the system. One model of the coronary artery will contain a coronary stent. The pressure of the fluid will be studied along its path using a series of pressure sensors and a camera will visualise the flow. The same experiments will be repeated on the ground with the same conditions as the in-flight model for comparison. The paper will outline in detail the design and development of the AIM experiment cube and the results of testing. The full data and results will be available after the completion of the mission which is expected to be between March and June 2020

Quartiere castello a Nichelino, Masterplan

pubblicato in: Torino, Atlante dell'architettura 1984/2008, Allemandi, Torin