One of the main concerns we had while developing our synthetic biology project was to determine in which way our biofilm could be used and who would be using it, in order to evaluate its impact on society. The field which would benefit the most of a nerves redirection while reducing the risk of infection, was orthopedic surgery, targeting patients suffering amputation.
Investigating Infection During Surgery
In medicine, surgery is a very common procedure. According to the data available, gathered by the Royal College of Surgeons, around 4.7 million surgical procedures were performed in 2014 in England; meaning that 7% of the total population is impacted by surgery. In the United States of America, according again to data gathered by the 2010 Ambulatory Medical Care Survey (NHAMCD), 48.23 million surgical procedures were performed in 2010. That’s around 14.8% of the total population. 5% of patients undergoing surgery develop surgical site infections (SSIs), which may cause substantial morbidity that can endanger a patient’s life, increase the number of days in the hospital and increase healthcare costs. SSIs are defined as infections that occur within 1 year if an implant is being placed.
We wanted to understand what goes on during a surgical procedure, what types of precautions were taken and what were the impacts of an infection for the patient. Thus, we began contacting surgeons and associations to learn more.
European Hospital Georges-Pompidou (HEGP) in Paris
The European Hospital Georges-Pompidou is the newest and biggest Parisian hospital. It opened in 2001, receiving the name of one of the French Presidents, Georges Pompidou. It’s one of the most efficient hospitals in Europe, illustrating itself by being the first cardiac transplant facility on the continent.
At the HEGP, we learned about the methods used to minimize the risks of infection, as well as how the surgeon was approaching those risks for the patients. With authorization from Dr. Benjamin Bouyer, we also had the chance to observe a team of surgeons during a spine implant operation. It became clear to us that even though every step was taken to eliminate the risk of infection, it could be useful to develop a system to minimize one step further this risk in the case of an implant.
Interview with Dr. Benjamin Bouyer
Dr. Benjamin Bouyer’s main concern with our project was how we would be incorporating the biofilm inside the patient. Indeed, every implant is given to the surgeon in a sterile way, inside a bag the doctor would not open until the very last moment. He also brought up the issue of our system being 3 in 1. Indeed, our biofilm would be capable of reducing the risk of infection by Staphylococcus aureus but would also be modified to induce the growth of nerves when needed, all this while conducting a signal. Indeed, our project is focusing on amputated patients, meaning only they would need all the three branches of our system. We reassured him by explaining that our system could also be used only for its inhibition of virulence properties and that it could be open to every type of patient. He did, however, believe that our project could be useful to many branches of medicine. We also asked him if he would, as a surgeon, use our device if the laws changed about the use of GMOs, and his response was very positive. Indeed, in his opinion, no doctor would reject a system proven to reduce infections.
Dr. Benjamin Bouyer is a surgeon at the HEGP specialized in lumbar rachis surgeries. He is currently clinical assistant head at the hospital and is also part of the “Société Française de Chirurgie du Rachis” or in english the “French Society of Rachis Surgeries”.
The Institut Pasteur
Dr. Jean-Marc Ghigo is the head of the Genetics of Biofilms Unit at Institut Pasteur. He is interested in the mechanisms involved in infections independent of a material, and infection linked to an implanted material.
Interview with Pr. Jean-Marc Ghigo.
Pr. Jean-Marc Ghigo was the first professional to talk to us about the formation of biofilms. In addition to his help with lab biofilm growth protocols, he also gave us great advice concerning our device and the confinement of our biofilm. Indeed, biofilms have a tendency to colonize the system and we needed to think of a way to confine them so they don’t disperse in the patient’s body or contaminate other material during the integration of the implant. By confining the biofilm, we would also reduce the chances of bacterial conjugation between possible pathogenic bacteria and ours.
Investigating Neural Connections and Prostheses
ICM
The “Institut du Cerveau et de la Moelle épinière” - ICM (Brain and Spine Institute), is an international brain and spinal cord research center in Paris whose innovative concept and structure make it the only institute of its kind in the world. The ICM brings patients, doctors, and researchers together with the aim to develop treatments for disorders of the nervous system and enable patients to benefit from them as quickly as possible.
Interview with Dr. Bernard Zalc, Ph.D
Dr. Bernard Zalc is co-leader of the oligodendrocyte development and neurovascular interactions department. He studies oligodendroglial cell development in the embryonic brain and the interactions between neural cells and the cerebral vascular network.
Dr. Bernard Zalc facilitated our understanding of the nerve growth and explained to us some issues that we could encounter. He gave us some tips regarding nerve growth and the connection between the nerve and our interface. Indeed, for him, other neurotrophins (like BDNF and VEGFA) and chemoattractant molecules are needed in order to attract and direct the growth toward the implanted interface of our system. We exposed to him our experimental approach for the proof of concept and he talked about the importance of the Schwann cells and the myelinization for the conduction. Moreover, he shared contacts which can help us regarding the modeling parts and the prosthesis.
SORBONNE UNIVERSITÉ
Sorbonne University is a multidisciplinary, research-intensive and world-class academic institution. Firmly rooted in the heart of Paris, it is committed to the success of its students and devoted to meeting the scientific challenges of the 21st century.
Dr. Jean-Marc Victor is a researcher at Sorbonne University. He is currently Director of Research at the CNRS, the French National Center for Scientific Research and is also working for the group “Multiscale Modeling of Living Matter at the Laboratory of Theoretical Physics of Condensed Matter.
Interview with Jean-Marc Victor, Ph.D.
Dr. Jean-Marc Victor was a real help for our modeling team. After presenting him the project, that he was very fond of, he helped us with the modeling of the growth of the neurons when we faced problems. His dynamism and interest for our project really helped us to finish our modeling, and in consequence, our in vitro primary culture.
ADEPA
ADEPA stands for “Association de Défense et d’Etude des Personnes Amputées », which translates to « Association for the Defense and Study of Amputated Persons ». This national association was created in 1996 and aims to unite forces between disabled persons. They represent the community during ministerial commissions and try to help people in their daily lives with their handicap by giving support and finding solutions.
Jean-Pascal Hons-Olivier is a country security Manager and member of the board of directors of ADEPA. As a leg amputee who underwent multiple corrective surgeries on his leg, Mr. Hons-Olivier is very involved in ADEPA.
Interview with Jean-Pascal Hons-Olivier
Mr. Jean-Pascal Hons-Olivier gave us great input on the different causes of amputation and the relationship between a patient and his prosthetist. He also allowed us to understand what was the process of getting an implant in France, how someone is living with an amputated limb and also gave his opinion on the different type of prosthesis on the market. He also talked about the type of prosthesis our system would integrate into: osseointegrated prostheses. The type of surgery is currently not taken in charge by the French health care system due to the high risk of infection, and breaking of the bone and the prosthesis, and only one surgeon is doing this type of operation in the country: Dr. Marion Bernard. Mr. Hons-Olivier did raise up some concerns about our project being too innovative since only a few industries in the USA are working on bionic prostheses and this type of surgery costs more around 100 000 euros at the moment.
CERAH
Thanks to Jean-Pascal Hons-Olivier’s generosity and his prosthetist, Didier Azoulay, we visited CERAH, the center of studies and research on equipment for disabled persons. We attended a course on prostheses with students in physical therapy. Also, we had the opportunity to see a step of prosthesis fabrication: namely stump molding for its sleeve. During this afternoon, we discovered osseointegration as a surgical technique to implant the prosthesis. Most of the time, the arm or leg’s prostheses aren’t integrated into the body but just attached to the body by a silicon sleeve which maintains the device by creating the vacuum. We understood that this method causes an excessive transpiration due to the sleeve and can generate pain on the bone’s end. Encouraged by these observations and due to the fact that we need a physical link between the body’s inside and the prosthesis, we chose osseointegration to NeuronArch project.
i.CERAM
i.CERAM based in Limoges, France, was founded in 2005 and is designing, manufacturing and marketing high-tech implants for various joints of the human body. The marriage of different ceramic materials and processes is one of the main features of the company. Thus, the clinical experience, combined with compressive strength qualities, osseocompatibility or decreased friction ceramics are exploited in the design of new implants of the company. The best seller of the company is a ceramic implant charged in antibiotics.
Porous Ceramic
Prosthesis made of polished ceramic
Interview with Dr. Eric DENES, Dr. Evelyn Poli and Dr. Christelle Arico
Dr. Eric Denes is an infectious diseases specialist at the University Hospital of Limoges and is the scientific director of i.CERAM. Dr. Evelyn Poli is a chemistry research and development engineer and Dr. Christelle Arico is a project manager at i.CERAM.
Dr. Eric Denes, as well as Dr. Evelyn Poli and Dr. Christelle, were very interested in our project. They are currently designing new materials in ceramic, titanium, and stainless-steel to test the bacterial adhesion on their prostheses. They warned us about the use of metals for the prostheses since S. aureus and P. aeruginosa tend to form biofilms easily on metals rather than on ceramic. They are also using Gentamicin and Vancomycin charged implants to cure infections. Their system does have a long half-life time (4 days) whereas our biofilm could be a longer-term solution.
IRAMIS
IRAMIS is at the Saclay Institute of Matter and Radiation and is the second institute in size of the CEA Fundamental Research Division. Inside IRAMIS there are projects directly linked to nanoscience for the technology of information and health, the interaction between matter, radiation and low-carbon energy applications.
Interview with Dr. Bernard Geffroy
We contacted Dr. Bernard Geffroy to learn more about OLED and to see if we could integrate the technology he is currently working on inside the prosthesis. It could be a way to let the patient know if S. aureus is present at the junction site of its osseointegrated prosthesis. Dr. Bernard Geffroy did go along the sayings of Mr. Jean-Pascal Hons Olivier on our project, mentioning it as being a bit innovative for now on. At first, we wanted to know if he thought the integration of a flexible screen inside the prosthesis, letting the patient know at every moment his/her health data, was possible. Dr. Bernard Geffroy did applaud for our ideas but doesn’t think this technology would be on the market for at least 10 or 20 years. He did redirect our ideas towards the use of OLEDs and color codes and was really interested in the following of our project.
Dr. Bernard Geffroy is currently working at the IRAMIS on OLED and flexible panels technology. OLED stands for Organic Light-Emitting Diode, in which the emissive electroluminescent layer is a film of organic compound that emits light in response to an electric current.
PARIS CITY HALL (Mairie de Paris)
The Paris City Hall is the headquarters of municipal and departmental representatives. In 2024, after 100 years, Paris will be hosting once again the Olympic games and Paralympic games. The city hall has 3 priorities toward this event. First, to create a more just society for everyone, where nobody is left aside. Second, a better participation and social integration of handicapped people. Third, to increase the spectator’s and partner’s interest for the Paralympic games.
Contact with Cyril Cartron and Marion Liard
Cyril Cartron and Marion Liard are two members of the Paris City Hall. Cyril Cartron works for the DICOM (Direction of Information and Communication) and deals with all events organized by the City Hall, especially sporting events. Marion Liard is a project manager in the Town Communication department. Her actions are particularly devoted to handicap.
Since NeuronArch is a project directly linked to handicap, we decided to get involved with the Mairie de Paris to make Paris a more accessible town for disabled people by creating new markings and signs in direct connection with the Paralympic games. For this, we contacted the Paris City Hall to make this project in collaboration, especially in preparation for 2024 Paralympics in Paris.
First, we contacted Cyril Cartron by phone. He was determined to help us. He gave us the contact of Marion Liard, in charge of handicap events. After some emails, she put us in contact with the cabinet of Nicolas Nordman, deputy mayor of the Paris City Hall, responsible for all issues concerning disabled people and their accessibility. This cabinet will contact us for a conciliation meeting, the December 3rd, to discuss with specialists during the International Handicap Day. Thus, we are eager to do this meeting with them!