Artificial arteries to improve the study of disease

Small wind­ing paths or blood high­ways, ves­sels are essen­tial ele­ments of bio­logy. Long con­sidered as simple por­ous pipes by physiology, they turn out to be involved in com­plex phys­ic­al and bio­chem­ic­al mech­an­isms that Abdul Barakat’s team is study­ing in the Hydro­dynam­ics Labor­at­ory (Lad­HyX).

We are devel­op­ing arti­fi­cial arter­ies and ves­sels to study the form­a­tion of bio­lo­gic­al phe­nom­ena, such as dis­eases, on dif­fer­ent scales. The aim is to take into account a factor often neg­lected by mod­ern bio­logy: the flu­id mech­an­ics in arter­ies. We have thus devised two mod­els, which can be adap­ted and applied to mul­tiple med­ic­al questions.

The first is formed from a col­la­gen hydro­gel base form­ing a tube of 3 mil­li­metres intern­al dia­met­er and 4.5 mil­li­metres extern­al dia­met­er. Smooth muscle cells and endotheli­al cells, which form nat­ur­al arter­ies, are intro­duced into the tube. The res­ult is an arti­fi­cial ves­sel that closely resembles a coron­ary artery, which sup­plies the heart with oxy­gen. This mod­el rep­res­ents a very high-pres­sure flow regime with shear. It is inten­ded to study coron­ary artery dis­ease, also known as atherosclerosis. 

In order to char­ac­ter­ise the cel­lu­lar response to the induced mech­an­ic­al factors, it is pos­sible to make use of high-res­ol­u­tion ima­ging sys­tems, such as con­focal fluor­es­cence micro­scopy, as well as imped­ance sensors. By pla­cing these sensors on the wall of our arti­fi­cial arter­ies, we pro­duce a true spa­tial­isa­tion that accounts for the cel­lu­lar dynam­ics involved. This approach makes it pos­sible to account for the dynam­ics of cel­lu­lar responses or inter­ac­tions between the dif­fer­ent types of cells in the vas­cu­lar wall. 

This sys­tem is, for example, deployed in col­lab­or­a­tion with the Uni­ver­sity Hos­pit­al of Lille in order to meas­ure the pro­duc­tion and dis­tri­bu­tion of the Wil­l­eb­rand factor involved in the form­a­tion of throm­bos­is, which can clog blood ves­sels. It also enables the Uni­ver­sity of New South Wales in Sydney to study the effect of tur­bu­lence on arter­i­al walls and the EFS in Stras­bourg to study the form­a­tion of plate­lets in the blood.

At Lad­hyx, this mod­el is help­ing us to under­stand the heal­ing of a ves­sel dur­ing the inser­tion of a stent, the small springs used to cor­rect a vas­cu­lar nar­row­ing. The pro­ced­ure can dam­age the endotheli­al cells that line the ves­sel lumen, cre­at­ing a risk of “sten­os­is”, a col­lapse of the vas­cu­lar walls. By anti­cip­at­ing the heal­ing char­ac­ter­ist­ics of each type of stent, we hope to avoid this phe­nomen­on¹.

The second type of mod­el, still based on col­la­gen hydro­gel, has dia­met­ers of 120 to 150 µm² and allows the rep­res­ent­a­tion of microvas­cu­lar dis­eases such as hyper­ten­sion or Alzheimer­’s dis­ease. In the case of Alzheimer­’s dis­ease, this brain patho­logy is often con­sidered as a dis­ease caused by the abnor­mal beha­viour of pep­tides (tau or β‑amyloid). How­ever, this rep­res­ent­a­tion has not led to real clin­ic­al advances des­pite sig­ni­fic­ant invest­ment over the last few dec­ades. Now, the idea is emer­ging that Alzheimer­’s dis­ease may res­ult from a microvas­cu­lar dis­order. Labor­at­or­ies have shown a cor­rel­a­tion between this dis­ease and cereb­ral hypo­p­er­fu­sion, i.e. abnor­mal blood flow in the brain.

In some anim­al mod­els, it is pos­sible to manip­u­late per­fu­sion of the brain. In this way, it is pos­sible to observe degen­er­a­tion of neur­ons and an accu­mu­la­tion of the pep­tides asso­ci­ated with Alzheimer­’s dis­ease. We there­fore sus­pect that an anom­aly in mech­an­ic­al factors par­ti­cip­ates in the devel­op­ment of the dis­ease or may even ini­ti­ate it. Our mod­els make it pos­sible to study this ques­tion by rep­res­ent­ing a ves­sel in all its com­plex­ity, with the dif­fer­ent types of cells that make it up or are shared with it in the brain. We can even vary the cell com­pos­i­tion to rep­res­ent dif­fer­ent bio­lo­gic­al situations.

In gen­er­al, our mod­els open up the study of the bio­lo­gic­al effects of mech­an­ic­al forces. It is known that such factors can modi­fy the expres­sion of pro­teins. There is there­fore a dimen­sion of mech­an­ic­al-bio­chem­ic­al inter­ac­tions that we are seek­ing to explore.

Interview by Agnès Vernet