Like the three mus­ke­teers who, as every­one knows, were four, Anne-Vir­ginie Sal­sac, direc­tor of research at the CNRS in the Bio­me­chan­ics and Bio­engi­neer­ing Lab­o­ra­to­ry (BMBI), Pro­fes­sor Jean-Paul Cou­etil and Dr Éric Bergoënd, both car­diac sur­geons, and Adrien Laperrousaz,then an engi­neer­ing stu­dent at the UTC, designed an inno­v­a­tive implant for the treat­ment of func­tion­al mitral insuf­fi­cien­cy. The implant is already patent­ed nation­al­ly and is await­ing approval for a Euro­pean exten­sion patent. 

It all began in 2014 with an e‑mail sent to Cécile Legal­lais, direc­tor of UTC-BMBI, by Pro­fes­sor Jean-Paul Cou­etil, then head of the tho­racic and car­dio­vas­cu­lar surgery depart­ment, and his col­league, Doc­tor Éric Bergoënd, both car­diac sur­geons at the CHU Hen­ri-Mon­dor of Créteil. They explained the con­cept of a new type of car­diac implant and want­ed to put their idea into prac­tice with the help of BMBI researchers and engi­neers. The e‑mail was sent to Anne-Vir­ginie Sal­sac and led to a meet­ing to assess the fea­si­bil­i­ty of the project.

“They were look­ing for peo­ple spe­cialised in bio­me­chan­ics, with skills in med­ical device tech­nol­o­gy and bio­engi­neer­ing, famil­iar with the world of research and who could col­lab­o­rate with them. In short, for a research team with the abil­i­ty to see the needs from a clin­i­cal point of view and capa­ble of propos­ing device ideas, design them and sup­port the project through to com­ple­tion. It was at a meet­ing held short­ly after­wards that they explained to us the prob­lem of func­tion­al mitral insuf­fi­cien­cy, its seri­ous con­se­quences from a clin­i­cal point of view, par­tic­u­lar­ly on patients who can­not tol­er­ate exist­ing devices”, explains AnneVir­ginie Salsac. 

We there­fore had to think about oth­er solu­tions. “Dis­cov­er­ing means defin­ing the prob­lem or issue pre­cise­ly. They are the ones that, depend­ing on your state of mind, you have the cer­tain­ty that there will be var­i­ous pos­si­ble solu­tions. It’s up to the team to try to find the best one,” says Jean-Paul Cou­etil, who has sev­er­al patents in car­diac surgery to his cred­it. It’s impor­tant to rec­og­nize that he’s come from a good school, since he was one of the last stu­dents of Pro­fes­sor Alain Car­pen­tier, a lead­ing spe­cial­ist in mitral repara­to­ry surgery and mitral valve repair at the Brous­sais Hos­pi­tal. A field that he con­tin­ued to explore when he joined the CHU Hen­ri-Mon­dor in 2010 as head of department. 

What rea­sons led Jean-Paul Cou­etil and Éric Bergoënd to think about a new sys­tem? “There are two types of mitral insuf­fi­cien­cy: organ­ic mitral insuf­fi­cien­cy and func­tion­al mitral insuf­fi­cien­cy. In the first case, the mitral valve that is struc­tural­ly defec­tive. In short, the valvu­lar tis­sues, pil­lars or cords attached to the left ven­tri­cle which may be defec­tive. In the sec­ond case, it is the valve func­tion that is dam­aged but not the struc­ture itself. A func­tion that may be impaired due to an anom­aly in the anato­my of the valve. In prin­ci­ple, the valve allows blood to flow in one direc­tion only from the left atri­um to the left ven­tri­cle, like a dou­ble non-return valve. How­ev­er, when the two sheets of the valve, for exam­ple, no longer come ful­ly into con­tact dur­ing the con­trac­tion of the ven­tri­cle, some of the blood flows back into the atri­um, mak­ing the heart less effi­cient as a pump. This can even­tu­al­ly lead to heart fail­ure, i.e., a severe defi­cien­cy of the ven­tric­u­lar mus­cle. This is all the more crit­i­cal that some patients can­not tol­er­ate exist­ing treat­ments”, explains Pro­fes­sor Couetil. 

So, how did the idea of a new type of implant come to be? “Pro­fes­sor Cou­etil’s par­tic­u­lar­i­ty is to have sev­er­al ideas per minute. We often dis­cuss patholo­gies for which exist­ing treat­ments are either inef­fec­tive or too inva­sive, and how to improve patient care. We have been par­tic­u­lar­ly inter­est­ed in the treat­ment of func­tion­al mitral insuf­fi­cien­cy, which is due to a dete­ri­o­ra­tion in valve func­tion char­ac­terised by an imper­fect con­tact between the two leaflets of the valve in sys­tole. It was dur­ing dis­cus­sions on this top­ic in 2011–2012 that he launched the idea of com­pen­sat­ing for this lack of con­tact by fill­ing the unwant­ed space between the leaflets with an implantable device; the exact nature of the device had not yet defined,” says Dr Éric Bergoënd. 

Until now, the only exist­ing tech­nique for repair­ing a defec­tive valve in a “min­i­mal­ly inva­sive” way (tran­scu­ta­neous­ly, with­out open­heart surgery) con­sists of plac­ing a small clamp con­nect­ing the two valve leaflets in the mid­dle. This pro­motes improves the con­tact between the two sheets, but it does dis­turb the func­tion­ing of the valve and the blood flow. 

And what about the par­tic­u­lar­i­ty of the project being car­ried out with­in UTC-BMBI…“Once the prob­lem was defined, we thought that the design of a new device con­sist­ing of re-estab­lish­ing the valve’s tight­ness was an ide­al project for set­ting up a research project for engi­neer­ing stu­dents as part of their train­ing. This is how a project team was set up, bring­ing togeth­er heart sur­geons Jean­Paul Cou­etil and Éric Bergoënd, mul­ti­dis­ci­pli­nary groups of UTC stu­dents (bac+3 to bac+5) and some UTC-BMBI research sci­en­tists,” empha­sis­es Anne-Vir­ginie Sal­sac, adding “We formed groups of 5–6 stu­dents who worked on the project over a six-month peri­od. Of course, as lec­tur­er-cum­re­search sci­en­tists, we mon­i­tored the project at reg­u­lar meet­ings with them to check that it was mov­ing in the right direc­tion and to pro­vide the stu­dents an appro­pri­ate lev­el of impetus.” 

As a 4th year engi­neer­ing stu­dent in mechan­i­cal engi­neer­ing, Adrien Laper­rousaz served, accord­ing to Dr Sal­sac, as a guide through­out the entire project. “Until then, I had only been inter­est­ed in mechan­ics in the sense of the sci­ence of move­ment of mech­a­nisms and had nev­er approached the med­ical field,” says Adrien Laper­rousaz. “In Feb­ru­ary 2014, Anne-Vir­ginie Sal­sac sub­mit­ted a CC-project sub­ject (“PR” in UTC jar­gon) on the ded­i­cat­ed UTC dig­i­tal work­space around this new mitral valve repair device. I was inter­est­ed and was select­ed among the five stu­dents for the start of the first PR ded­i­cat­ed to the car­diac implant. I was the only one from mechan­i­cal engi­neer­ing, the oth­er four from bio­engi­neer­ing, and the only one to mas­ter the design soft­ware to do 3D mod­el­ling. This makes it pos­si­ble to cre­ate more mean­ing­ful visu­als. We then met, accom­pa­nied by AnneVir­ginie Sal­sac, the two sur­geons who described their idea to us and we set to work for five months”, Adrien Laper­rousaz explains. 

“Once the CC is over, what can you do?” he won­dered. All the more so as the four oth­er class mates had left for their final intern­ship. Hav­ing tak­en a lik­ing for what he was doing, he decid­ed to reap­ply in Sep­tem­ber 2014. Being the only one present from the begin­ning and the only one who had mas­tered the state-of-the-art for this project, we decid­ed to set up sev­er­al PR groups — one group work­ing on mate­ri­als, for exam­ple; anoth­er on the patient sta­tus, etc.”, he says. “In Jan­u­ary 2015, we realised that we had enough mate­r­i­al to put togeth­er a dossier and start look­ing for fund­ing to devel­op pro­to­types,” he says. 

Thus, in March 2015, Adrien and his col­leagues sub­mit­ted an appli­ca­tion to the nation­al I‑Lab com­pe­ti­tion in the cat­e­go­ry “Emerg­ing Projects” and were declared lau­re­ates, in May 2015. At the end of the com­pe­ti­tion, they received a grant of 25 000 euros. This allowed UTC to finance Adrien’s final intern­ship at the UTC Daniel Thomas Inno­va­tion Cen­tre. “It was in Sep­tem­ber 2015, dur­ing this intern­ship, that I start­ed to devel­op a pro­to­type implant in order to be able to car­ry out in vit­ro tests”, adds Adrien Laperrousaz. 

The inno­v­a­tive approach devel­oped by this UTCCNRS team con­sists in restor­ing the valve’s tight­ness by attach­ing an inflat­able bal­loon to one of its leaflets, via a tran­scu­ta­neous insert route. 

“The cre­ation of a new sys­tem is always accom­pa­nied by a phase of exper­i­men­ta­tion. In short, we want­ed to see how it works in the most real­is­tic con­di­tions pos­si­ble. Hence the idea of implant­i­ng the pro­to­type in vit­ro, on an exper­i­men­tal heart mod­el — at Uni­ver­si­ty Col­lege Lon­don (UCL) — which repro­duces the flow of blood as in a human heart. The patholo­gies linked to the mitral valve were also repro­duced to be as close as pos­si­ble to real­i­ty. These tests were suc­cess­ful, as there was a real reduc­tion in resid­ual leak­age. This enabled us to pro­vide a proof of con­cept,” describes Anne-Vir­ginie Sal­sac. What moti­vat­ed the choice of UTC? “A col­league who has devel­oped sev­er­al projects in the field of biotech­nol­o­gy advised us to call on the engi­neers and researchers of the UTC if we want­ed this project to suc­ceed. An opin­ion shared by a teacher-researcher from the École poly­tech­nique whom I had con­tact­ed and who gave me the names of Cécile Legal­lais and Anne-Vir­ginie Sal­sac. They both praised the dynamism of UTC and assured me that we would find real skills in bio­engi­neer­ing there,” explains Éric Bergoënd. It took a lot of ener­gy for the whole team to come up with such a suc­cess­ful con­cept and work on the draft­ing of the patent claim. But the adven­ture is not over giv­en that a Cifre PhD stu­dent, Thibaut Alleau is pur­su­ing — under the super­vi­sion of Anne-Vir­ginie Sal­sac, in part­ner­ship with the com­pa­ny SEGULA Tech­nolo­gies — the cre­ation of a dig­i­tal mod­el of the dynam­ics of the mitral valve, enabling the posi­tion­ing of implants to be mod­elled and tested.