Probleemstelling:

In bypass surgery for atherosclerotic stenosis of limb arteries and coronary arteries, an autologous segment of a blood vessel is the conventional vascular graft used. However, pre-existing pathological conditions of the vascular system can lower the availability of appropriate grafts. Synthetic grafts, made from materials such as polytetrafluoroethylene, are an alternative for autologous grafts. However, synthetic grafts have a low patency due to surface thrombogenicity in the acute setting and development of neointimal hyperplasia in the long term. Tissue engineered vascular grafts can improve the patency by providing biochemical signals that prevent these complications.

Additionally, the tissue engineering of organs can be a solution for the lack of donor organs in transplant surgery. To engineer organs in vitro, the biofabrication of vasculature is essential. Without any form of vascular integration, tissues thicker than 100-200 μm struggle to survive and proliferate due to the diffusion limits of nutrients and oxygen. The vascular integration within large tissues should comprise microvasculature (< 0.1 mm) that overcomes this diffusional limit and macrovasculature (> 0.1 mm) that permits fast perfusion of the whole construct after anastomosis to the host’s vasculature. In context of the Ghent Advanced therapies & Tissue Engineering (GATE) initiative, a project has been set up for the 3D bioprinting of macrovasculature for organ culture and treatment of cardiovascular diseases.

Doelstelling:

The student will help with the development of an advanced flow bioreactor that can mimic the physiological shear stress and biaxial (circumferential and axial) stretch during physiological pulsatile flow. The separate components of the flow bioreactor (Pump, flowchamber, tubing and the macrovasculature design – see fig. A) will be adapted towards these physiological conditions based on computational fluid dynamics. For the adaptation of the macrovasculature design, the student will help with the modelling and the 3D bioprinting of the vessels in sterile conditions using the Regemat BioV1 3D bioprinter (see fig. B). Additionally, the student will optimize the sterile operation of the flow bioreactor: the system needs to be easy to assemble and it should be practical to refill the culture medium reservoir within a laminar flow cabinet. The different components of the flow system should be able to resist steam sterilization to guarantee sterility during the experiment. Also, the student will investigate the most optimal position within a CO2 incubator without disrupting the incubator operation. If necessary, an alternative for the CO2 incubator system needs to be found.

Figure 1: A) Illustration of a biaxial flow bioreactor system: (1) schematic top view of the flow chamber. (2) image of macrovasculature grafts inside the flow chamber. (3) A schematic of the flow chamber connected to both a linear motor and peristaltic pump to generate cyclic biaxial stretching. Adapter from huang et al (2016). B) Regemat BioV1 3D bioprinter