Biomaterials: What are we looking for? · 2017. 11. 10. · Poster Session – Abstract List 21 Thanks to our Sponsors 41 2 . CBS-QCSC 2 nd Symposium, Quebec City, October 27 th 2017

CANADIAN BIOMATERIALS SOCIETY QUEBEC CITY STUDENT CHAPTER

2nd SYMPOSIUM

Biomaterials:

What are we looking for?

Friday October 27th, 2017

Université Laval, COPL building: room 1168

Quebec City, QC, Canada

Electronic Abstract Book

CBS-QCSC 2nd Symposium, Quebec City, October 27th 2017

Table of Contents

Welcome Message from the Faculty Advisor of the CBS-QCSC 3

Mot de bienvenue du conseiller facultaire du CBS-QCSC 4

Welcome message from the President and Vice-President of the CBS-QCSC 5

Mot de bienvenue du président et vice-président du CBS-QCSC 6

Organizing Committee 7

Symposium information 8 Map of the Symposium 9

Program of the Symposium 10

Session 1: Orthopaedics Biomaterials 11 Lecture 1: Virginie Gauvreau 11 Lecture 2: Geoffroy Rivet-Sabourin 12 Lecture 3: Thomas Willett 13

Session 2: Vascular Biomaterials 14 Lecture 1: Jean-François Tanguay 14 Lecture 2: Stephen Pacetti 16 Lecture 3: Diego Mantovani 17

Session 3: Skin Substitutes 18 Lecture 1: Geneviève Mercier-Couture 18 Lecture 2: Jean-Philippe Therrien 19 Lecture 3: François Berthod 20

Poster Session – Abstract List 21

Thanks to our Sponsors 41

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Welcome Message from the Faculty Advisor of the CBS-QCSC

Welcome to the second symposium organized by the CBS-QCSC!

Once again, this year, the CBS-QCSC student-researchers have joined forces to set up a symposium that, I am convinced, will be of exceptional quality. As you can see, the CBS-QCSC is a unique forum in which scientific, clinical and industrial expertise is combined to develop the biomedical devices of tomorrow.

In recent years, the Canadian Society of Biomaterials has taken a prominent place in the global research area in the biomedical sector. The success of the last World Congress held in Montreal in May 2016 may be taken as an example. Part of this success is most certainly due to the deep motivation that led to the founding of the CBS in 1973, that is training of young researchers in an area of knowledge essential to the Canadian society and economy.

Today, CBS is the victim of its own success as student chapters abound across Canada with organizations in British Columbia, Alberta, Ottawa, Kingston, Montreal and of course, in Quebec City. This is an eloquent proof that CBS students are committed to developing their society and have taken all means to ensure its development.

I am particularly proud to act as the advisor to the CBS-QCSC. Over the past year, I have been able to appreciate the incredible dynamism of the Quebec chapter, which multiplies conferences and scientific activities of all kinds. While it is clear that all Canadian chapters are dynamic, and at the risk of being labeled chauvinism, I would state without hesitation that the CBS-QCSC is by far the most energetic student chapter in Canada!

As proof, the CBS-QCSC proposes a particularly high-profile scientific forum, which brings together actors from clinical, academic and industrial circles in various key research sectors in the field of biomaterials. I foresee animated discussions and why not, future collaborations?

I invite you to take advantage of this opportunity to forge professional, scientific, or just friendly links with participants in this forum. The opportunities are enormous and require only to be exploited.

I conclude by thanking the members of the organizing committee who have deployed treasures of imagination to allow this day to be held.

I wish you an excellent symposium!

Gaétan Laroche, PhD, FBSE Faculty advisor

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Mot de bienvenue du conseiller facultaire du CBS-QCSC

Je vous souhaite la plus cordiale des bienvenues au second symposium organisé par le CBS-QCSC !

Encore une fois cette année, les étudiants-chercheurs du CBS-QCSC ont uni leurs efforts pour mettre sur pied un colloque qui, j’en suis convaincu, sera d’une qualité exceptionnelle. Comme vous pourrez le constater, le CBS-QCSC constitue un forum unique à l’intérieur duquel les expertises scientifiques, cliniques et industrielles sont jointes pour développer les dispositifs biomédicaux de demain.

Au cours des dernières années, la Société Canadienne des Biomatériaux a pris une place prépondérante sur l’échiquier mondial de la recherche dans le secteur biomédical. On prendra pour exemple le succès remporté par le dernier congrès mondial qui s’est tenu à Montréal en mai 2016. Une partie de ce succès est très certainement attribuable à la motivation profonde qui a conduit à la fondation du CBS en 1973, à savoir la formation de jeunes chercheurs dans un domaine du savoir essentiel pour la société et l’économie canadiennes.

Aujourd’hui, le CBS est en quelque sorte victime de son succès et les chapitres étudiants foisonnent partout à travers le Canada avec des organisations en Colombie-Britannique, en Alberta, à Ottawa, à Kingston, à Montréal et bien entendu, à Québec. Il s’agit d’une preuve éloquente que les étudiants membres du CBS ont à cœur le développement du CBS et ont pris en mains les rennes pour en assurer le développement.

Je suis particulièrement fier d’agir à titre de conseiller du CBS-QCSC. Au cours de la dernière année, j’ai pu apprécier le dynamisme incroyable du chapitre de Québec, qui multiplie les conférences et les activités scientifiques de toutes sortes. Même s’il est clair que tous les chapitres canadiens sont dynamiques, et au risque d’être taxé de chauvinisme, j’affirmerai sans hésitation que le CBS-QCSC est de loin le chapitre étudiant le plus énergique au Canada !

À preuve, le CBS-QCSC nous propose aujourd’hui un forum scientifique particulièrement relevé, qui met en scène des acteurs des milieux cliniques, académiques et industriels dans divers secteurs de recherche clés du domaine des biomatériaux. J’anticipe des discussions animées et pourquoi pas, de futures collaborations ?

Je vous invite donc à profiter de l’occasion qui vous est offerte pour tisser des liens professionnels, scientifiques, ou tout simplement amicaux avec les participants à ce forum. Les opportunités offertes sont énormes et ne demandent qu’à être exploitées.

Je termine en remerciant les membres du comité organisateur qui ont déployé des trésors d’imagination pour permettre la tenue de cette journée.

Je vous souhaite un excellent colloque !

Gaétan Laroche, PhD, FBSE Conseiller facultaire

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Welcome message from the President and Vice-President of the CBS-QCSC

Dear colleagues, dear conference delegates,

On behalf of the Organizing Committee, it is our immense pleasure and honor to welcome you to Quebec City to the Second Symposium of the Quebec City Student Chapter of the Canadian Biomaterial Society (CBS-QCSC).

The theme of the Symposium is “Biomaterials: What Are We Looking for?”. A rather peculiar title that tries to reflect the mission of our Organization and what we think is one of the main need in the biomaterial community: a more profound discussion between researchers, clinicians and industry, which are the main players in this fascinating research field.

With this in mind, the Organizing Committee conceived an event where the academic, clinical and industrial perspectives in the orthopaedic, vascular and skin fields are contemplated and where time is mainly spent on discussion, rather than classical lectures followed by a few minutes of questions.

This format, originated directly from the desires of the students of the Chapter, envisages nine lectures from internationally renowned speakers coming from Canada and the United States and three discussion panels. Finally, a networking cocktail with a poster session will close the day. Altogether, more than 5 hours will be dedicated to scientific discussion, making this day a great opportunity to share research, experience and points of view. It is also the perfect time to develop new collaborations and promote cooperation among academia, clinics and industry.

We would like to convey heartfelt thanks to the speakers who kindly accepted our invitation to animate this conference and to all our sponsors that made this event possible and free for all participants. We also thank professors and research associates who agreed to play a special part in this day as chairman or jury member.

It is important to acknowledge and emphasize that this event is the result of the passionate work of CBS-QCSC members. Our deepest thanks go particularly to the members of the Organizing Committee and to all our collaborators who have been dedicating their spare time to the planning and management of this initiative for more than a year. A special word of thanks to our current and former Faculty Advisors, Prof. Gaétan Laroche and Prof. Diego Mantovani, who always thoroughly trusted, supported and guided the Chapter in this adventure.

Finally, thanks to all of you for being here, contributing with your participation to the success of this event.

Wishing you an interesting, enjoyable and fruitful experience at this meeting,

Daniele Pezzoli Morgane Laurent President of CBS-QCSC Vice-President of CBS-QCSC

Chairs of the CBS-QCSC 2nd Symposium

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Mot de bienvenue du président et vice-président du CBS-QCSC

Chers collègues, chers participants,

Au nom du Comité Organisateur, c’est avec un immense plaisir et honneur que nous vous accueillons à Québec pour ce Second Symposium du Chapitre Étudiant de Québec de la Société Canadienne des Biomatériaux (CBS-QCSC).

Le thème du Symposium est « Biomatériaux : Que recherchons nous ? ». Ce titre un peu particulier essaye de refléter la mission de notre Organisation et ce que nous pensons être le principal besoin au sein de la communauté des biomatériaux : une discussion plus profonde entre chercheurs, cliniciens et industriels, qui sont les acteurs clés de ce champ de recherche fascinant.

En gardant cela en tête, le Comité Organisateur a conçu un évènement où les perspectives académiques, cliniques et industrielles des domaines orthopédique, vasculaire et plastique sont évaluées et où la majorité du temps est dédiée à la discussion, à l’encontre des conférences plus classiques suivies de quelques minutes de questions.

Ce format, directement issu de l’imagination des étudiants du Chapitre, propose 9 présentations de conférenciers internationalement reconnus, venant du Canada et des États-Unis, et 3 discussions-débats. Enfin, un cocktail de réseautage accompagné d’une session d’affiches scientifiques clôturera la journée. En tout, plus de 5 heures seront dédiées à la discussion scientifique, rendant ainsi ce jour une belle opportunité de partager vos recherches, expériences et points de vue. C’est aussi le moment parfait pour développer de nouvelles collaborations et encourager la coopération entre l’académie, le milieu clinique, et l’industrie.

Nous aimerions adresser nos plus sincères remerciements aux conférenciers qui ont gentiment accepté notre invitation pour animer cette conférence et à tous nos sponsors qui ont rendu cet évènement possible et gratuit pour tous les participants. Nous remercions de plus les professeurs et professionnels de recherche qui ont bien voulu jouer un rôle particulier en tant que chair de session ou membre du jury.

Il est important de mentionner que cet évènement est le résultat du travail passionné des membres du CBS-QCSC. En particulier, nos plus profonds remerciements vont aux membres du Comité Organisateur et à tous nos collaborateurs qui ont dédié leur temps libre à la planification et à l’élaboration de cette initiative depuis plus d’un an. Un merci tout particulier à nos conseillers facultaires présent et passé, Prof. Gaétan Laroche et Prof. Diego Mantovani, qui ont su faire confiance, supporter et guider le Chapitre dans cette aventure.

Finalement, merci à vous tous d’être ici et de contribuer par votre participation au succès de cet évènement.

En vous souhaitant une expérience intéressante, enrichissante et fructueuse lors de cette rencontre,

Daniele Pezzoli Morgane Laurent Président of CBS-QCSC Vice-Président of CBS-QCSC

Chairs of the 2nd CBS-QCSC Symposium

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Organizing Committee

Program Directors Daniele Pezzoli Morgane Laurent

Faculty Advisor Gaétan Laroche

Scientific Committee Dimitria Bonizol Camasao Josy Baldaheani Naud Nawel Ghribi Souhaila Ghadhab

Logistics Caroline Loy

Natalia Milaniak Amna Amri

Ruchi Sharma

Communication Jean-François Sauvageau Linda Bonilla Sergio Agustin Diaz Rodriguez

Fundraising Francesco Copes Jad Mousselli Samira Ravanbakhsh

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Symposium information

Registration and information desk The registration desk will be in COPL building in front of room 1168 and will be open: Friday 27th October 2017: 9:00-17:00 Symposium proceeding Guidelines for speakers

Presentations should be uploaded on the computers in the symposium room. Members of the organizing committee (yellow name tag) will assist you to upload and preview your presentations. Please upload your presentation at least 5 minutes before the start of your session. Guidelines for poster holders

Posters will be presented during the networking cocktail in the Atrium at Alexandre-Vachon building starting at 17:00. Please hang your poster on the corresponding poster panel. Poster numbers can be found in the book of abstracts. Please do not forget to pick up your poster after the closing session. Awards: Posters will be judged during the posters session by members chosen by the organizing committee. Poster prices will be awarded at the end of the networking cocktail. Symposium networking cocktail The conference networking cocktail will take place at 17:00 in the Atrium at Alexandre-Vachon building. The location of the Alexandre-Vachon building can be found on the next page.

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Map of the Symposium

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Program of the Symposium

9:00 - 9:45

9:45 - 10:00

10:00 - 10:20Clinical perspective

Virginie Gauvreau, Gaspé Hôtel-Dieu Hospital

10:20 - 10:40Industrial perspective

Geoffroy Rivet-Sabourin, Bodycad

10:40 - 11:00Academic perspective

Thomas Willett, University of Waterloo11:00 - 11:45 Panel Discussion

11:45 - 13:00


Jean-François Tanguay, Montreal Heart Institute


Stephen Pacetti, Abbott Vascular

13:40 - 14:00Academic perspective

Diego Mantovani, Université Laval

14:00 - 14:45 Panel Discussion

14:45 - 15:00


Geneviève Mercier-Couture, CHU de Québec


Jean-Philippe Therrien, EnDev Laboratories

15:40 : 16:00Academic perspective

François Berthod, Université Laval16:00 - 16:45 Panel Discussion

16:45 - 17:00

17:00 - 19:30

Registration & Networking breakfast

Symposium closing

Networking cocktail with posters & exhibition

Alexandre-Vachon Building - Atrium

Session 1:

Orthopaedics

Biomaterials

Session 2:

Vascular

Biomaterials

Session 3:

Skin Substitutes

Welcoming from faculty advisor and president of the CBS-QCSC

Social Lunch

Coffee break

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Session 1: Orthopaedics Biomaterials

Lecture 1: Virginie Gauvreau

Brainstorming the Future of Orthopaedic Surgery

Abstract

The future of orthopaedic surgery implant design takes into account variables known from the past to be required for the ideal orthopaedic biomaterial such as inertia, non-toxicity, corrosion proof, great strength, high resistance to fatigue, inexpensiveness and ease of processing. In the past decade, these concepts lead to the development of various new implant designs and uses of new alloys that should revolutionize our world. However, more recently, fatigue failures attributed to corrosion at the trunnion-neck junction of newly designed hip prothesis, development of pseudo-tumours attributed to metallic ion release in big femoral head metal-on-metal hip replacement, evidences of systemic metal toxicity effects on patient’s vital functions, ceramic component fractures, rapid polyethylene wear accentuated by oxidation have been reported. Newly designed implants were recalled has they were associated with catastrophic consequences for the patients. From these lessons learned, we may still try to improve a fail design or material, or we could reinvent the future to design implants perfectly fitted for every case. Consider using modern imaging technologies, software solutions, robotic assistance implantation, personalized implant design and production, self regeneration promoting materials, intrinsic infection resistance and life lasting implants. There is no limit to our imagination but that of our past experience acquired anchored bias. Young researchers can make a difference precisely because they haven’t absorbed corporate conventions. Let’s brainstorm the future of orthopaedic implants!

Biography

Dr Virginie Gauvreau is an orthopaedic surgeon with a specialty in hip and knee reconstruction surgeries. After completing a bachelor degree in Biochemistry, she obtained a Masters degree in Experimental Medicine at the Biotechnologies and Bioengineering Unit of the Laval University Surgical Department working on the development of micropatterning printed activated biomaterial surfaces while completing a medical degree. She was board certified in orthopaedic surgery in 2012. She further completed a fellowship at the University of Western Ontario acquiring a strong experience in complicated hip and knee joint restoration while pursuing research at their renowned

orthopaedic biomaterial retrieval research lab. She presented at the world biomaterial conference on printing of activated peptides on PTFE Films to promote endothelialization and at the international symposium of regenerative medicine about micropatterning of cell signals onto biomaterial surfaces to improve endothelialization. Awarded by Laval University Surgical Department for research on determinant factors of pain, functional limitations and quality of life after a total knee replacement, and for study assessing metallic ions release in total knee replacements. Was previously granted by the Natural Sciences and Engineering Research Council of Canada and recently granted by the Current Concepts in Joint Replacement foundation.

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Lecture 2: Geoffroy Rivet-Sabourin

Custom Devices in Orthopedic: Changing the Way to Think about Patient Treatment and Surgical Procedure

Abstract

Since more than 30 years, the orthopedic domain treat patients with standard devices. We are currently at the beginning of a new revolution in this domain going from standard off-the-shelve products to patient specific products. This kind of product are currently available for niche procedures like complex revision or tumor treatment. Now, the number of players developing personalized primary knee, primary hip or primary shoulder is growing rapidly. This is now possible because of the new manufacturing techniques like 3D printing and also availability and improvements of the imaging machine like CT and MRI. What are benefits for the patients and health care system?

Biography Geoffroy Rivet-Sabourin is computer engineer. He has a master degree in computer vision and a PhD in medical imaging processing. He is currently Research Director at Bodycad where he is leading development of new products. M. Rivet-Sabourin also trains orthopedists around the world to use Bodycad technology. He is a member of the Standards Council of Canada for Bone and joint replacements. He has been working in medical technology research and development for more than 10 years with an emphasis on patient specific solutions using imaging technology.

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Lecture 3: Thomas Willett

"Biomaterials for Skeletal Reconstruction: What Are We Looking for?"

Abstract

Reconstruction of large structural defects in the skeleton is a significant clinical challenge with unmet needs. Large structural defects can result from tumour resection, infection resection, traumatic fractures, and even revision arthroplasty. If the defect is large enough (critically sized), bone biology is insufficient to close the gap and a therapeutic intervention is required. Current options include metal prostheses and allograft-based approaches. Various structural biomaterials and tissue engineered products are in development. Metal prostheses and allograft have high failure rates due to mechanical issues, uncontrolled resorption, infection and non-union. In this presentation, Prof. Willett will discuss his groups work on cortical bone as a high performance biomaterial, allograft bone as a structural biomaterial, and current endeavors to develop 3D printable, bone-mimetic nanocomposite biomaterials in order to offer a robust solution to the large structural defect problem.

Biography

Thomas L. Willett, PhD, PEng, is an Assistant Professor in the Biomedical Engineering program in the Department of Systems Design Engineering at the University of Waterloo. He has recently established his new Composite Biomaterial Systems Laboratory, which includes facilities for composite biomaterials formulation, additive manufacturing (3D printing) using biomaterials, thermomechanical testing, and state-of-the-art mechanical testing. He trained in mechanical engineering at Queen's University (BASc, 2001;

MASc, 2003) and received his PhD (tissue mechanics) from the School of Biomedical Engineering at Dalhousie University in 2008. He worked on bone and orthopaedics research at Mount Sinai Hospital/University of Toronto from 2007-2015. During that time, he developed a patented method for protecting the mechanical properties of bone from damage that occurs during irradiation sterilization used in tissue banking. His research interests include: mechanics of biomaterials and skeletal tissues (especially cortical bone), development of composite biomaterial systems for use in skeletal reconstruction, and biomedical technology design and innovation.

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Session 2: Vascular Biomaterials

Lecture 1: Jean-François Tanguay

From Pre-Clinical to Clinical Development of the Bioresorbable Scaffold: A 25 Years Discovery Journey

Abstract

Since Gruentzig’s first percutaneous balloon angioplasty in 1977, significant advances have been made in the percutaneous treatment of coronary artery disease. The development of bare metal stents (BMS) addressed the issue of acute vessel closure, and while BMS prevented elastic recoil and constrictive remodeling, high rates of in-stent restenosis remained because of neointimal hyperplasia. This prompted the development of drug eluting stents (DES), which were able to reduce the incidence of in-stent restenosis with the addition of anti-proliferative drugs to the stent platform, thereby reducing the occurrence of neointimal hyperplasia. Safety issues were however described with the first generation of DES, when a new entity of late stent thrombosis became a significant problem, with risk quoted at 0.6% per year. Second generation DES, with more biocompatible antiproliferative drugs and thinner struts/improved designs were able to significantly decrease the incidence of major adverse cardiac events and late stent thrombosis. Newer bioresorbable scaffolds were designed to overcome some limitations of DES. The presence of a metallic structure that will forever remain in the vessel comes at a cost: decreased vaso-reactivity/impaired physiology of the artery, prevention of positive remodeling, obstruction of the side-branch by stent struts, impaired lesion imaging with computed tomography of magnetic resonance, and inability to insert a coronary bypass graft at the site a stent was implanted. This led to the development of bioresorbable scaffolds (BRS), that would theoretically allow for the benefits of transient scaffold support by preventing acute vessel recoil/closure, but overcome the limitations of metallic stents such as impaired vasomotor response, and late stent thrombosis, while facilitating repeat treatments of the lesion site. The development of BRS technology has been an extraordinary journey with opportunities for engineers, scientists and interventional cardiologists to interact and address multiple challenges.

Biography Dr. Jean-Francois Tanguay is an expert in Interventional Cardiology with a strong interest in translational research. He is involved in undergraduate and postgraduate medical training and CME education. Dr. Tanguay is Director of the Coronary Unit at the Montreal Heart Institute and Clinical Cardiologist, combining work in the emergency room, the coronary care unit, the outpatient clinic and the catheterization laboratory (1995-ongoing). He is Director of the MD-PhD and Interventional Cardiology Training Programs and professor at the Faculty of Medicine of the Universite de Montreal. He was President of the Canadian Interventional Cardiology Association (2002-2005)

and Director of the Interventional Cardiology Montreal Symposium (2004-2015). He is Fellow of the Royal College of Physicians and Surgeons of Canada (FRCPC), the Canadian Cardiovascular Society (FCCS), the American Heart Association (FAHA), the American College of Cardiology (FACC), and the

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European Society of Cardiology (FESC). Dr. Tanguay is Chair of the CCS Anti Platelet Guidelines Committee and their guidelines’ recommendations were published in the Canadian Journal of Cardiology in 2011, 2013 with an updated version in 2017. His research is focused on understanding the interactions between platelets, leukocytes and endothelial cells in order to improve vascular healing. Dr. Tanguay’s investigations brought promising discoveries related to 17beta-estradiol and the specific contribution of estrogen receptors in vascular healing. During his research fellowship, Dr Tanguay studied the early prototypes of bioresorbable drug eluting stents platforms in pre-clinical and thrombosis models. With his colleagues at MHI, he performed the first coronary implantation of a drug-eluting bioresorbable scaffold (ABSORBTM) in North-America. Dr. Tanguay is member of steering committees for NIH-, CIHR- and industry-sponsored clinical trials. He has written 180 papers in peer-reviewed journals, 6 book chapters & guidelines, and 266 abstracts & posters. He has given more than 250 invited lectures or oral presentations at national and international scientific meetings. His research team received more than $40 million from academic and from other granting agencies. In addition to his clinical, teaching and research background, he is the father of four teenagers, and has been happily married for 26 years.

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Lecture 2: Stephen Pacetti

Developing New Cardiovascular Biomaterials Applications: Challenges and Successes with the XIENCE and Absorb Coronary Implants

Abstract

Percutaneous coronary intervention is a major, and often preferred, option for the treatment of coronary artery disease. Restoration of coronary flow is the primary objective and stenting of coronary lesions is widely done. Coronary stents have improved steadily since they were introduced in the 1980s. However, further improvements are still sought for lowering restenotic and thrombotic complications. The cardiovascular biomaterials that go into stents must meet multiple stringent criteria for biocompatibility, mechanical properties, processability and regulatory requirements. Two case studies will be presented focusing on the XIENCE drug eluting fluoropolymer coating and the bioresorbable polylactide polyester polymers used in the ABSORB totally bioresorbable coronary stent. The XIENCE fluoropolymer coating, combined with the antiproliferative drug everolimus, represents a new application for fluoropolymer implants and has advanced the performance of drug eluting stents. ABSORB was the first totally bioresorbable stent to be approved. Its goal is to provide improved long-term outcomes compared to permanent coronary stents. The development process, and experimental data, which led to these products will be summarized.

Biography

Stephen D. Pacetti joined Abbott Vascular in 2005 as a Biomaterials Manager of Research and Development. Currently, he is a Senior Principal Scientist of DES Technologies. Previously, he was a Technical Advisor at Guidant Vascular Intervention, where he worked in the areas of controlled drug delivery and cardiovascular biomaterials. With the goal of a better stent alloy than stainless steel, Mr. Pacetti’s research into high strength and radiopaque alloys resulted in selection of CoCr L-605 for the MULTI-LINK VISION coronary stent. He studied multiple drug eluting stent coating polymers for biocompatibility, drug delivery and

processability. The result of this team development was the PVDF-HFP based fluoropolymer drug delivery coating of the XIENCE coronary stent. For the Absorb program, he played a key role in bioresorbable polymer characterization and degradation chemistry. He currently works on next-gen drug delivery stents, endovascular therapies, and biological response to coronary implants. Mr. Pacetti received a Master’s degree in chemical engineering from the University of Houston and a Master’s degree in physical-organic chemistry from the University of California, Berkeley. He has been granted 365 U.S. patents, authored six scientific publications, and presented on multiple occasions for physician groups, regulatory agencies and at scientific meetings.

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Lecture 3: Diego Mantovani

Vascular Biomaterials: What Are We Looking for? An Academic Perspective

Abstract

Over the last 50 years, biomaterials, prostheses and implants saved and prolonged the life of millions of humans around the globe. Today, nano-biotechnology, nanomaterials and surface modifications provide a new insight to the current problem of biomaterial complications, and even allow us to envisage strategies for the organ shortage. In this talk, the portrait of what are we looking for the next generation of vascular biomaterials will be discussed. Focusing on biodegradable metals, the academic perspective of what does developing a new class of biometals mean will be presented. Finally, what might be a suitable model for academic teams working in the biomaterial and the biomedical field aiming clinical translation will be illustrated. Few real examples from joint academic/industrial/clinical partnership will complement the portrait.

Biography

Holder of the Canada Research Chair Tier I in Biomaterials and Bioengineering for the Innovation in Surgery, professor at the Department of Min-Met-Materials Engineering at Laval University, adjunct director at the Division of Regenerative Medicine of the Research Center of the CHU de Québec, Diego Mantovani is a recognised specialist in vascular biomaterials. At the frontier between engineering, medicine and biology, within his team, their works aim to improve the clinical performances of medical devices for functional replacement, and to envisage the next generations of biomaterials to develop

artificial organs enhancing the quality of the life of patients. In 2012, he was nominated Fellow of the International Union of Societies for Biomaterials Science & Engineering (FBSE) for his leadership and contribution to biomaterials for medical devices. He was Executive Co-Chair of the 10th World Biomaterials Congress 2016. He is advisor of few medical devices consortium in the Americas, Asia and Europe.

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Session 3: Skin Substitutes

Lecture 1: Geneviève Mercier-Couture

Skin Grafts and Skin Substitutes

Abstract

Scarring and wound contraction are the first mechanisms in place to heal a skin wound. For large wounds, this process leaves the body at risk of infection, hypothermia and articular contracture that can affect functionality. Wounds that are left open can also degenerate into skin cancer. For these reasons, methods that facilitates wound coverage or resurfacing are desired.

Biography

Geneviève Mercier Couture is a plastic surgeon with a specialty in reconstruction. She completed her plastic surgery training at Université de Montréal and was board certified in June 2016. She then did a microvascular surgery fellowship at MD Anderson Cancer Center, Houston. She is now part of the plastic surgery team working at CHU de Quebec where she gets to treat burn patients frequently.

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Lecture 2: Jean-Philippe Therrien

Industry Perspective on the Use/Need of Human Engineered Skin Models for Topical Product Development

Abstract

Since its conception more than 30 years ago, tissue engineering has made significant progresses, especially in the field of human skin. Tissue engineering of the human skin was initially developed for clinical/treatment purposes, but quickly recognized as a powerful tool for the different phases of research and development of dermatological products. Different variations of human skin equivalent have been developed to test safety and efficacy of active ingredients and topical products. In the over-the-counter/cosmetic industry, these models have been validated to test the product safety in order to replace animal use. In the pharmaceutical industry these models have become of a particular interest to de-risk topical drug development of new drugs and optimize formulation development. The use and the application of these different models will be discussed as well as their limitations.

Biography

JP joined EnDev Laboratories in November 2016 having held positions of increasing responsibility as Director of Skin Biology with the Dermatology Therapeutic Area at GlaxoSmithKline (GSK), previously Stiefel, a GSK company and Stiefel. Prior to joining Stiefel/GSK, JP spent 6 years at the National Cancer Institute/National Institute of Health on the Dermatology Branch as Post-Doctoral and Research fellow working on human skin gene therapy. JP received a B.S. in Biochemistry from University of Sherbrooke (Quebec, Canada) and Ph.D. in Molecular & Cellular Biology/Photobiology from Laval University (Quebec, Canada). JP brings more than 20 years of

experience in dermatological research and more than 8 years of experience in topical product development for both, prescription (Rx) and consumer healthcare/cosmetic (Cx) products, where his work has been extensively published in high-impact journals, scientific presentations, patent applications, and sale aids. JP is also a member of the Board of Directors of the Society of Investigative Dermatology.

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Lecture 3: François Berthod

Development of a Vascularized, Innervated and Immunocompetent Tissue-Engineered Human Skin

Abstract

The main purpose of my research is to use tissue engineering techniques of in vitro organ reconstruction to study different diseases that can be induced or modulated by the nervous system to better understand their mechanism and find new therapeutic approaches. We have produced a model of innervated reconstructed skin to investigate the influence of various parameters on sensory innervation of skin physiology, such as angiogenesis or inflammation. We then developed skin models to recapitulate in vitro the phenotypes of skin pathologies such as diabetic ulcers and psoriasis, using cells from patients in order to assess the role of sensory nerves in these diseases. We have also established a model to grow motor neurons in three dimensions and to promote the migration of axons while achieving their myelination by Schwann cells. These neurons can then be combined with astrocyte and microglia to mimic the spinal cord. This model is being developed to reproduce the in vitro process of motor neurons degeneration in amyotrophic lateral sclerosis, using cells derived from mice developing the disease, or ALS patients’ cells.

Biography

François Berthod obtained his PhD in Biomedical Engineering from the Lyon 1 University, France. He is currently full Professor at the Department of Surgery, Faculty of Medicine, Université Laval, and researcher at the Centre LOEX de l’Université Laval, centre de recherche du CHU de Québec-Université Laval in Quebec City, Canada.

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Poster Session – Abstract List

1. Advanced Multilayered Multiculture Vascular Tissue Models Using Collagen-Based Scaffold

Caroline Loy, Daniele Pezzoli, Diego Mantovani

2. Surface Modification with Chitosan Biopolymer for the Prevention of Bacterial Contamination Devices

Clayton Campelo, Juliana Vaz, Pascale Chevallier, Marisa Beppu, Diego Mantovani

3. The Influence of Cell Seeding Density on the Maturarion of Collagen-Gel Based Scaffolds

Dimitria Camasao, Daniele Pezzoli, Lucie Lévesque, Caroline Loy, Diego Mantovani

4. Development of a Novel Nanofibrous Collagen Scaffold for Tissue Engineering by Coaxial Electrospinning

Dimitria Camasao, Nele Pien, Daniele Pezzoli, Diego Mantovani, Sandra Van Vlierberghe, Peter Dubruel

5. A Convergent Strategy in the Regioselective Modification of a Glycoconjugate with Biologically Active Natural Product-Derived Structures

Eric Hong, Rosaire Mongrain, Vamsy Chodavarapu, Chao-Jun Li

6. Assessment of the Biocompatibility of Dense or Porous Chitosan-Based Scaffolds

Fernanda Carla Bombaldi de Souza, Renata Francielle Bombaldi de Souza, Ângela Maria Moraes, Diego Mantovani

7. Colloidal Suspensions of Platinum Group Metal Nanoparticles (Pt, Pd, Rh) Synthesized by Dielectric Barrier Discharge Plasma (DBD)

Jean-François Sauvageau, Stéphane Turgeon, Pascale Chevallier, Marc-André Fortin

8. Surface Plasma Engineering for the Controlled Release of Silver Ions for Antibacterial Applications

Linda Bonilla-Gameros, Maxime Cloutier, Stephane Turgeon, Pascale Chevallier, Vanessa Montaño-Machado, Diego Mantovani

21


9. Improvement of Interface bBetween Stainless Steel 316L and Plasma Deposited Fluorocarbon Nano Coating by an Amorphous Oxide Layer

Mahrokh Dorri, Stephane Turgeon, Pascale Chevallier, Maxime Cloutier, Diego Mantovani

10. Investigations on Glycol-Chitosan Particles for Vocal Fold Tissue Engineering Applications

Miral Toufaili, Neda Latifi, Meisam Asgari, Rohit Gopinath, Luc Mongeau

11. Development of Nanostructured Thin Films for Solar and Biomedical Applications

Natalia Milaniak, Paul Brunet, Francoise Massines, Gaétan Laroche

12. Greffage de la Fibronectine et du Peptide RGD sur des Prothèses en Titane pour Favoriser l’Adhésion des Cellules Épithéliales

Nawel Ghribi, Souhaila Ghadhab

13. A Novel Injectable Biomaterial for Vocal Fold Tissue Engineering Neda Latifi, Meisam Asgari, Luc Mongeau

14. Low Temperature Plasma-Based Processes for Innovative Textiles Pascale Chevallier, Ranna Toluei, Stéphane Turgeon, Lucie Lévesque, Diego Mantovani

15. Oxide Layer Optimization and Direct Plasma Amination of L605 Alloy for its Application in Cardiovascular Devices.

Sergio Diaz-Rodriguez, Pascale Chevallier, Carlo Paternoster, Diego Mantovani

16. Cellularized Collagen-Chitosane Biomaterial used as a Model for the Studying of the Glycation on Wound Healing

Thiéry De Serres-Bérard, Sabrina Bellenfant, Francois Berthod

17. Properties of Chitosan-Xanthan Based Membranes for Orthopedical Applications

Cristiano Rodrigues, Fernanda Bombaldi de Souza, Renata Bombaldi de Souza, Ângela Maria Moraes, Márcia Rosângela Wink, Diego Mantovani

18. Interaction of Red Blood Cells and Platelets with Fe-Mn-Ag Alloy Pedram Sotoudehbagha, Mehrdad Khakbiz, Saeed Sheibani, Hendra Hermawan

23 22


Poster Abstract 1

Advanced Multilayered Multiculture Vascular Tissue Models Using Collagen-Based Scaffold

Caroline Loy, Daniele Pezzoli, Diego Mantovani

Université Laval

Introduction: Engineered vessel walls have the potential to be used instantly as an in vitro model of vascular tissue for the investigation of patho/physiological processes and as preclinical tests for drugs and devices. Herein, we describe the development of a collagen-gel based tri-culture model closely mimicking the tri-layered cellular organization of native arteries. Methods: Cellularized collagen gels were prepared as reported elsewhere1. A tri-step process was developed to produce the tri-layered construct. The external (adventitia) layer was composed of fibroblasts (FBs) at a density of 106 cells/ml within collagen; the middle (media) layer of smooth muscle cells (SMCs, 106 cells/ml); the innermost (intima) layer was obtained by seeding a monolayer of endothelial cells (ECs, 80 000 cells/cm2) over the media layer. A rotating bioreactor was used to seed ECs in the lumen of tubular systems. The degree of endothelialisation of the construct was investigated by fluorescence microscopy, phenotypic protein expression of calponin and alpha-actin by SMCs by western blot, and the blood compatibility of constructs by clotting time assay. Also, histological staining of transversal sections was performed to observe the organization of the construct and of the produced extra-cellular matrix. Results and discussion: A tri-culture model of vascular wall with a hierarchical organisation in multi-layer and a complete monolayer of ECs within 24 h for the flat model2 and 48 h for the tubular model3 was developed. The organisation in two cellularized collagen gel layers and the presence of a monolayer of ECs was observed in microscopy. After 7 days, the compaction of the collagen matrix by vascular cells was achieved, and the deposition of ECM components such as fibronectin and fibrillin-1 was observed. The ECs formed a continuous monolayer over the construct and did not migrate inside the collagen. The blood compatible functionality of the EC monolayer was demonstrated by the clotting time assay showing that after 7 days of maturation clotting was prevented, with a concentration of free hemoglobin higher than 80% after 60 min of incubation (p > 0.05 between the endothelialized constructs and the non-endothelialized constructs). Also, western blot results suggest that SMCs lose their contractile phenotype in the mono-culture while the contractile phenotype was not significantly affected in the tri- and bi- culture with a heterogeneous population of synthetic and contractile SMCs after 7 days of culture. Mechanical properties showed that the tri-culture demonstrate an higher elastic behavior that the mono-culture of SMCs. Conclusion: The design of an in vitro vascular wall model in disk and tubular shape using collagen as scaffold was reported. This tri-culture engineered tissue promotes cell-matrix remodeling and improves the anticoagulant surface properties. This model is expected to allow the investigation the mutual intimate relationships existing among vascular cells thus representing a step forward into the engineering of in vitro vascular tissue models. References: 1. Meghezi, et al., J. Vis. Exp., 2015, e52812 2. Loy, et al., Biomater. Sci., 2017, 5, 153 3. Loy et al., Biotechnol. J., 2017, in press

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Poster Abstract 2

Surface Modification with Chitosan Biopolymer for the Prevention of Bacterial Contamination Devices

Clayton Campelo1, Juliana Vaz1,2, Pascale Chevallier3, Marisa Beppu2, Diego Mantovani1,3

1Laboratory for Biomaterials and Bioengineering - ULaval, 2University of Campinas, 3CR-CHU de Québec - Université Laval

Introduction: Bacterial contamination is a public health and socio-economic problem. In Canada, 220,000 people develop nosocomial infections each year, 8,000 will die and $106.4 million are spent1. The surface of materials is responsible for the spread of bacterial contamination. To prevent contaminations, the development of antimicrobial surfaces is investigated. Chitosan is a promising candidate for the development of new functionalized biomaterials because it is a natural nontoxic polymer with interesting properties: biocompatibility and antimicrobial action2,3. In this work polytetrafluoroethylene films (PTFE) were functionalized using plasma treatment and poly(ethylene glycol)bis(carboxymethyl) (PEGb) was used to link chitosan molecules aiming to obtain an antibacterial surface. Methods: PTFE films (0.25 mm of thickness; 3.0 x 3.0 cm2) were washed with acetone, deionized water, and methanol in an ultrasonic bath. In order to recover the surface films with chitosan, samples were aminated by atmospheric DBD plasma, then grafted by PEGb, activated with EDAC in MES buffer. The activated film was reacted during 3 h with chitosan at 2% w/v, in an aqueous solution of acetic acid 1% (v/v). Samples were washed with water before use. Surface modifications were assessed by X-Ray Photoelectron Spectroscopy (XPS) for surface chemical composition, by Water Contact Angle (CA) for wettability and by Scanning Electronic Microscopy (SEM) for surface morphology. Results and discussion: XPS results demonstrated that the surface modifications were successful. Indeed, after plasma treatment (N2/H2), 6.7% of nitrogen was detected and PEGb grafting was evidenced by the decrease of fluorine as well as the increase of the oxygen and carbon elements. Chitosan grafting, with its polysaccharide structure, was indicated by highest carbon, nitrogen, and oxygen percentage with a decrease in fluorine concentration. PEGb surfaces exhibited low contact angle values with water. In the case of chitosan-grafted surfaces, CA was lower than PEGb surfaces, mainly due to the introduction of polar functional groups present in chitosan structure. These modifications were also shown by SEM images that depicted a homogeneous coating without the formation of clusters or domains on the surface of PTFE. Conclusion: Results showed that plasma treatments combined with grafting of PEGb and chitosan are potential techniques for the achievement of functionalized coatings. The surface modification is showed by an increase of nitrogen, carbon, and oxygen percentage and a decrease of fluorine atomic concentration, present on the bare PTFE surfaces. PEGb-CHI coatings provide a good coverage of the PTFE surfaces suggesting that this is a good candidate to obtain antibacterial devices. Thus, the next step is to investigate the antibacterial effect of this coating on Escherichia coli as well as Staphylococcus

aureus.

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Poster Abstract 3

The Influence of Cell Seeding Density on the Maturation of Collagen-Gel Based Scaffolds

Dimitria Camasao, Daniele Pezzoli, Lucie Lévesque, Caroline Loy, Diego Mantovani

Laboratory for Biomaterials and Bioengineering, CRC-I, Dept Min-Met-Materials Eng & Research Center of CHU de Québec, Laval University, Quebec City, Canada

Introduction: Vascular tissue engineering (VTE) relies on the cellularization of scaffold materials with the ultimate aim to produce artificial living artery equivalents overcoming the drawbacks of current vascular grafts. Type I collagen gel, main component of native vessel extracellular matrix (ECM), has been widely explored as a scaffold material owing to its favorable biological properties. The use of an ECM protein-based scaffold increase the similarity of the construct with a native vessel, however, one of their recurrent discrepancy is the cell density, about two orders of magnitude. In addition, the influence of cell seeding density on the maturation of collagen gel constructs is one parameter often overlooked in VTE. In this light, herein, the influence of SMC seeding density on the static maturation of tubular collagen gels was investigated in terms of cell-mediated compaction, gene expression for some key ECM proteins and mechanical properties. Methods: Human umbilical artery SMCs were mixed in collagen type I solution2 supplemented with a neutralizing buffer solution to obtain final cell densities of 0.5, 1.5 and 4.5×106 cells/mL. The solution was poured in tubular molds and cultured at 37oC for 1, 3 and 7 days. Masson trichrome staining and real-time PCR technique, using TaqMan® Gene Expression assay for collagen, elastin, fibrillin-1 were applied for structural and biological characterization respectively. The mechanical properties were evaluated through circumferential stress-relaxation tests. Results and discussion: SMC-mediated compaction of collagen gels was accelerated by increasing cell density but the final volume tended to achieve a plateau after 7 days of maturation. Histological staining confirmed the differences in cell density and compaction of the structure. Real time PCR analyses showed an upregulation of collagen, fibrillin-1 and elastin expression with higher cell density. The differences found in ECM remodelling and deposition lead to improvements in the mechanical properties of the construct, evaluated in terms of initial and equilibrium elastic modulus (EE). The higher cell density condition (4.5×106cells/mL), led to a EE of ca 60 kPa after 7 days of static maturation, approaching values reported in literature for carotid arteries3. Conclusion: These results showed that increasing SMC seeding density accelerates cell-mediated compaction and improves ECM protein expression in collagen gels. Altogether, higher cell densities unequivocally resulted in higher mechanical properties of the cellularized constructs after one week of static maturation. References: 1. Meghezi, S. et al. Effects of a Pseudophysiological Environment on the Elastic and Viscoelastic Properties of Collagen Gels. Int J Biomat (2012). 2. Rajan, N. et al. Preparation of ready-to-use, storable and reconstituted type I collagen from rat tail tendon for tissue engineering applications. Nat Protocols 1 (2007). 3. Berglund, J. D. et al. Viscoelastic Testing Methodologies for Tissue Engineered Blood Vessels. J Biomech Eng 127 (2005).

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Poster Abstract 4

Development of a Novel Nanofibrous Collagen Scaffold for Tissue Engineering by Coaxial Electrospinning

Dimitria Camasao1, Nele Pien2, Daniele Pezzoli1, Diego Mantovani1, Sandra Van Vlierberghe2,3, Peter Dubruel2

1 Laboratory for Biomaterials and Bioengineering, CRC-I, Dept Min-Met-Materials Eng & Research Center of CHU de Québec, Laval University, Quebec City, Canada 2 Polymer Chemistry and Biomaterials Research Group,

Ghent University, Ghent, Belgium 3 Brussels Photonics, Vrije Universiteit Brussel, Brussels, Belgium

Introduction: Type I collagen, being the main component of native vessels, is a promising scaffold material for vascular tissue engineering (VTE) owing to its favorable biological properties and to the ability of cells to remodel its matrix.1 Material processing and the incorporation of cells into a scaffold are key factors in the field. Electrospun collagen scaffolds have the advantage of being fibrous structures of which the architecture mimics that of connective tissue. Furthermore, multi-component scaffolds composed of core-shell type fibers using concentric needles can also be obtained, providing the basis for an emerging concept of direct electrospinning of polymer and cells2. Herein, the optimization of single-needle and co-extrusion electrospinning using collagen type-I solutions was performed. For the co-extrusion technique, a cell-compatible collagen solution was used in the core to allow the subsequent direct incorporation of cells during the process. Methods: Collagen type I, obtained from rat tail tendon,3 was dissolved in acetic acid at different concentrations to be used in the shell. The cell-compatible solution for the core was obtained by dissolving the same collagen in acetic acid (0.2 wt%) supplemented with a neutralizing buffer solution. Single-needle and co-extrusion electrospinning were performed using an in-house designed electrospinning system. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FT-IR) were used to evaluate the impact of the processing technique on the material. Fiber diameter and morphology was evaluated by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and micro-computed tomography (µ-CT). Results and discussion: Electrospun collagen fibers were obtained after optimization of parameters including the collagen concentration for the shell (15 wt%), the applied solvent (40 % acetic acid in water), the flow rate (0.1 mL/h), the voltage (18 kV) and the distance from the needle to the collecting plate (12 cm). DSC, TGA and FT-IR analyses showed that the electrospinning process did not compromise the studied collagen properties. SEM images confirmed that collagen fibers using both single-needle and co-extrusion technique were obtained, with a smooth surface and a homogeneous cylindrical shape. The fiber diameter was in the range of 150-250 nm. Preliminary tests with cells mixed in the core demonstrated that they were deposited on the collecting plate with the collagen fibers. The core-shell structure will be further evaluated by TEM and confocal microscopy. Conclusion: Collagen fibers were successfully obtained by single-needle and co-extrusion electrospinning. Further characterizations such as TEM and µ-CT on samples with a stained core (Texas red dye) is in progress to confirm the core-shell structure. Optimization of co-extrusion electrospinning with cells is on going. References: 1. Seifu, D. G. et al. Nat. Reviews Card. 2013,10. 2. Jayasinghe, S. N. et al. Nanomed. 2007,2. 3. Rajan, N. et al. Nat. Protocols. 2007, 1(6), 2753-2758.

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Poster Abstract 5

A Convergent Strategy in the Regioselective Modification of a Glycoconjugate with Biologically Active Natural Product-Derived

Structures

Eric Hong1, Rosaire Mongrain1, Vamsy Chodavarapu2, Chao-Jun Li1

1McGill University, 2University of Dayton

Entering the dawn of the 21st century, the biomaterials field has undergone a key conceptual evolution in design intent; envisioned future third-generation biomaterials will henceforth be designed to elicit specific cellular responses at the molecular level, while retaining the design concepts of previous generations, namely: bioactive, bioresorbable, and 'bioinert', i.e., reduce to a minimum level the immune response and foreign body reaction.1 The last decade has witnessed impressive advances in synthetic strategies involving covalent conjugation and non-covalent methodologies including, but not limited to, hydrogel-based biomaterials.2 The regioselective modification of a glycoconjugate in the present study is inspired by the design concepts attributed to third-generation biomaterials, and seeks to address the current shortfalls in sensor encapsulation methodologies (limited, perhaps non-existent), by coupling molecules to solid supports, bestowing new biological functionalities at the molecular level to original materials, thus improving biosensors' in situ performance.3 More specifically, the regioselective modification incorporates the following important and useful structural motifs: The steric exclusion caused by extensive hydration,4 good conformal flexibility,4 and high chain mobility4 of ethylene glycol contributes to minimize non-specific protein adsorption,2,4 protein aggregation,2,4 cell adhesion,2 interfacial tension with biological fluids,2 and immunogenic response,2,4 thus ensuring that the substrate remains 'bioinert'. The use of a natural carbohydrate structure and bioactive amino sugar, known to be metabolized by certain human enzymes and incorporated into glycosaminoglycan or glycoprotein metabolic pathways,5 can potentially circumvent secondary effects in the host. Conversely, degradation products of synthetic bioresorbable materials have shown tendencies for such deleterious effects in the host. Lastly, an unreported heterocyclic structure derived from parent compounds whose privileged structural motifs possess established value in medicinal chemistry, is expected to be of potential therapeutic value. References 1. L. L. Hench and J. M. Polak, Science, 2002, 295, 1014. 2. N. Bhattarai, J. Gunn and M. Zhang, Adv. Drug Delivery Rev., 2010, 62, 83. 3. A. Rezania, R. Johnson, A. R. Lefkow and K. E. Healy, Langmuir, 1999, 15, 6931. 4. R. Heuberger, G. Sukhorukov, J. Vörös, M. Textor and H. Möhwald, Adv. Funct. Mater., 2005, 15, 357. 5. J. Mao, L. Zhao, K. de Yao, Q. Shang, G. Yang and Y. Cao, J. Biomed. Mater. Res., Part A, 2003, 64A, 301.

26 27


Poster Abstract 6

Assessment of the Biocompatibility of Dense or Porous Chitosan-Based Scaffolds

Fernanda Carla Bombaldi de Souza1, Renata Francielle Bombaldi de Souza1, Ângela Maria Moraes1, Diego Mantovani2

1University of Campinas - Brazil, 2U. Laval et CHU Qbc

Introduction: Scaffolds are artificial extracellular matrices, capable of supporting cell growth and three-dimensional tissue formation. Along with cells and growth factors, scaffolds are one of the three key components for tissue engineering. The chemical composition and structure of the scaffolds, together with their surface properties, may affect their biocompatibility, limiting their range of clinical applications. Interfacial free energy, surface hydrophilicity, presence of functional groups, density of charges and surface topography are among the characteristics of the scaffolds that affect their biological performance. Hemocompatibility and cytotoxicity are also important aspects of biocompatibility that need to be evaluated prior to scaffold implantation. In this work, different aspects of the biocompatibility of scaffolds constituted of nature-derived polymers were evaluated. In this sense, surface properties as roughness and hydrophilicity, as well as thrombogenicity and in vitro cytotoxicity were assessed for chitosan-alginate (Ch-A) and chitosan-pectin (Ch-P) scaffolds produced in the presence or not of the porogenic agent Kolliphor® P188 (K). Methods: Ch-A and Ch-P scaffolds containing or not 10% (w/w) of K were prepared by solvent casting. CaCl2 and NaOH were used for crosslinking and pH neutralization. Morphology was analyzed by SEM. Roughness (Rq) of the scaffold surface was determined using a portable rugosimeter with cutoff length set at 0.8 mm and total length at 5 mm. Surface hydrophilicity was analyzed by depositing a 2 μL drop of water on the surface of the scaffold and measuring the static contact angle. Thrombogenicity was assessed by the free hemoglobin method, using Teflon® as negative control. In vitro direct cytotoxicity tests were performed by placing 10 mm diameter scaffolds samples onto a monolayer of 3T3 cells (fibroblasts) and assessing cells viability after 1 day. As positive control, Triton X-100® was used in the culture medium. Results and discussion: Micro-scale roughness was observed for all formulations, with porous samples presenting more irregular surfaces. The surfaces of alginate-containing samples are more hydrophilic than those of the pectin-containing samples and the addition of K increases the hydrophilicity in both cases. For the hemocompatibility assessment, the free hemoglobin test was performed, in which red blood cells not entrapped in a thrombus formed in the sample surface are hemolyzed and free hemoglobin molecules are colorimetrically measured. The scaffolds presented between 68% and 95% of free hemoglobin when compared to the control Teflon®, commonly used in implantable devices. Ch-A formulations were found to be less thrombogenic than Ch-P, what can be attributed to their surface wettability, as the adsorption of blood proteins would be less intense over their more hydrophilic surface. In vitro direct cytotoxicity of scaffolds to fibroblasts varied from 15% and 30%. No trend for the influence of the addition of K to the scaffolds was observed on cytotoxicity. Conclusion: Considering the studied properties of the materials, all formulations presented satisfactory performance and each of them may be directed to particular applications in tissue engineering. Complementary studies on other aspects of the biomaterials biocompatibility should be performed to assure the feasibility of the use of these devices as implantable materials.

28


Poster Abstract 7

Colloidal Suspensions of Platinum Group Metal Nanoparticles (Pt, Pd, Rh) Synthesized by Dielectric Barrier Discharge Plasma (DBD)

Jean-François Sauvageau1,2,3, Stéphane Turgeon2, Pascale Chevallier2,3, Marc-André Fortin1,2,3

1Université Laval, 2CR-CHU de Québec - Université Laval, 3Centre de recherche sur les matériaux avancés

Introduction: Atmospheric-pressure plasmas produced by dielectric barrier discharge (DBD) can be used to nucleate and grow nanoparticles (NPs) of metals from the platinum group (PGM: Pt, Pd and Rh).[1-3] In this technology, plasma discharges are produced between a PGM-containing precursor solution acting as a liquid electrode, and a counter electrode located near its surface. The resulting effect is a nucleation and growth of surfactant-free ultra-small PGM nanoparticles, which is a significant advantage compared with conventional nanoparticle synthesis techniques. At this point however, little is known on the efficiency of continuous-flow DBD-based plasma electrochemistry systems to reduce PGM ions in solution. The rapidity and efficiency of DBD plasmas to reduce metal ions into solid nanoparticles is key to evaluate their potential both for the synthesis of pure and surfactant-free PGM nanoparticles, and for the extraction of PGM ions from liquid effluents (waste products, electrolytic solutions, etc).

Methods: The conversion rate of PGM ions into solid materials (nanoparticles) is compared for three acidic solutions of PGMs: platinum, palladium, and rhodium. Two types of plasma are used (Ar and H2), and the syntheses are tested with and without a surfactant (the polysaccharide dextran). NP growth is monitored in real time by using UV-Vis. The particle size of the nanoparticle solutions is measured by TEM and DLS, and elemental analysis is performed to quantify the percentage of nanoparticle conversion in each experimental condition. Results and discussion: For the optimum parameters of synthesis, the conversion yield of metal ions to nanoparticles is higher for palladium (99.20%), slightly less for rhodium (75.05%) and somewhat lower for platinum (51.44%). UV-visible spectroscopy analyzes showed that NPs are mostly formed during plasma treatment, indicating that reactive species fed or created in solution by plasmas are necessary for the reduction of metal ions. Conclusion: The results indicate that it is possible to synthesize colloidal PGM suspensions from synthetic aqueous solutions by continuous DBD plasma treatment. Alternatively, plasma electrochemistry could also be used to purify aqueous solutions from their content in PGM. References: [1]. Koo IG, Lee MS, Shim JH, Ahn JH, Lee WM. Journal of Materials Chemistry 2005, 15:38. [2]. McKenna J, Patel J, Mitra S, Soin N, Svrcek V, Maguire P, Mariotti D. European Physical Journal-

Applied Physics 2011, 56:2. [3]. Xu WY, Wang XZ, Zhou Q, Meng B, Zhao JT, Qiu JS, Gogotsi Y. Journal of Materials Chemistry 2012, 22:29.

29


Poster Abstract 8

Surface Plasma Engineering for the Controlled Release of Silver Ions for Antibacterial Applications

Linda Bonilla-Gameros, Maxime Cloutier, Stephane Turgeon, Pascale Chevallier, Vanessa Montaño-Machado, Diego Mantovani

Laboratory for Biomaterials and Bioengineering, CRC-I, Department of Min-Met-Materials Engineering, CHU de Québec Research Center, Université Laval, Québec, Canada

Introduction: Hospital-associated infections (HAIs) are caused by the transmission of pathogenic bacteria in a health care facility. Despite improvements in hygiene practices and disease prevention inside hospitals, HAIs continue to account as a major risk factor in serious health issues [1]. Bacteria have the ability to survive in a range of environments by forming adhered sessile communities protected in biofilms. Because of this, environmental surfaces play an important role acting as a reservoir and transmission vector of pathogenic microorganisms. Therefore, antibacterial surfaces have emerged as a primary approach in the mitigation of bacterial pathogens [2]. In this context, biocide-releasing coatings offer the advantage of embedding a bioactive element in a scaffold. However, one of the major challenges is controlling the release kinetics of the antibacterial compound [3]. Based upon these observations, this study presents plasma oxidation of Ag coating (Ag-PO) and nanocomposite coating (Ag-DLC) as novel surface engineering strategies to control the release of silver ions, as antibacterial agent. Methods: Plasma deposition and oxidation was carried out using a modified FLARION series system. Ag-DLC films were deposited by a three successive sequences plasma treatment: Ar etching, H2 activation and CH4 deposition with simultaneous Ag sputtering. Moreover, two different plasma oxidation treatments were implemented on Si samples with Ag coating: 1) Ar/O2 plasma post-treatment with 3 kJ and 15 kJ, and 2) reactive sputtering, by the addition of O2 simultaneously during sputtering of Ag target. Chemical characterization was carried by x-ray photoelectron spectroscopy, whilst physical characterization was analyzed by atomic force microscopy. Silver ion release from the treated surfaces was analyzed by microwave plasma atomic emission spectroscopy. Results and discussion: The results obtained after XPS analyses showed a direct relationship between silver content and silver ion released in DI water. Ag-DLC samples with the lowest silver content (2.7 at. %) released the least silver ions (9.7 μg/cm2), whilst Ag-PO with 36 at. % exhibited the highest release (62 μg/cm2). However, this statement proved to be true only for the first 24 hours. Indeed, AFM surface analysis demonstrated that roughness is a factor that may alter the kinetic of silver released, despite silver content in the sample: whereas Ag-DLC (3.6 nm) showed a slow but continuous release up to 7 days, Ag-PO (8.7 nm) showed an initially fast burst followed by a fast decrease until almost silver exhaustion. Conclusion: Surface engineering offers ability to tune the release and bioactivity of silver-containing coatings. References: [1] H.A. Khan, et al., Asian Pacific Journal of Tropical Biomedicine, 5, 7 (2015). [2] M. Cloutier, et al., Trends in Biotechnology, 33, 11 (2015). [3] M. Cloutier, et al., 9, 029013 (2014). [4] M. Dorri et al, Microsc. Microanal. 22 (2016).

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Poster Abstract 9

Improvement of Interface between Stainless Steel 316L and Plasma Deposited Fluorocarbon Nano Coating by an Amorphous Oxide Layer

M. Dorri, S. Turgeon, P. Chevallier, M. Cloutier, D. Mantovani

Laboratory for Biomaterials and Bioengineering, CRC-I, Department of Min-Met-Materials Engineering, CHU de Québec Research Center, Université Laval, Québec, Canada

Introduction: The interface of a polymeric coating/metallic substrate affects directly the adhesion of the coating to the substrate. Fluorocarbon (CFx) coatings, which are well-known for producing biocompatible surfaces, are applied on medical devices made of AISI 316L stainless steel (SS316L) [1]. Among different CFx/SS316L interfaces a plasma etched interface produced the highest adhesion of the CFx coating to the SS316 substrate. However, aging in an aqueous saline solution formed blisters on the coating [2]. The underlying mechanism was solution infiltration through the coating defects reaching the CFx/SS316L interface and the corrosion of the substrate [3]. In this work an amorphous oxide layer, as a new interface, on the SS316L substrate improved the stability and adhesion of the CFx coating. Methods: Disks of SS316L were modified in three steps: 1) removal of the native oxide layer by plasma etching (Etched), 2) producing a new oxide layer by plasma oxidation (PO), and 3) CFx plasma deposition. CFx was deposited on two interfaces: 1) plasma etched (Etched+CFx) and 2) plasma etched and oxidized (PO+CFx). Potentiodynamic polarization, aging, atomic force microscopy (AFM), and X-ray photoelectron spectrometry (XPS) were conducted to respectively investigate the corrosion properties, coating stability and adhesion, topography, and chemical composition of the samples. Results and discussion: After removing the defective native oxide layer from the SS316L surface, a new oxide layer was produced by PO. PO decreased the corrosion rate of samples more than 10-fold compared with Etched samples. This was explained by the amorphous microstructure of the PO oxide layer [4]. After aging in an aqueous saline solution, more blisters were formed on Etched+CFx than on PO+CFx samples. Since the blisters formation was caused by the production of corrosion materials, lower quantity of blisters showed higher resistance to corrosion of the PO interface and led to the improvement of the coating adhesion. The coating was more stable on the PO interface compared with the Etched one. In fact, defluorination of the coating was less in PO+CFx samples than in Etched+CFx samples, after aging. Moreover, the corrosion rate of PO+CFx and Etched+CFx samples decreased more than 5-fold and 2-fold compared with the uncoated samples. Producing a coating with less defects on the PO interface, which leads to lower solution infiltration into the coating, explains the enhancement of the coating stability. Conclusion: Adhesion of CFx coatings to SS316L substrate could be mainly enhanced by tailoring the interface properties. In this work, an amorphous oxide interface decreased the corrosion rate of both the substrate and the CFx coated samples, and decreased the blisters formation on the coating. These characteristics led to improvement of the adhesion and stability of the CFx coating to the SS316L substrate in an aqueous saline solution. References: [1] R. Mugica-Vidal et al, Appl. Surf. Sci. 347 (2015). [2] F. Lewis et al, ACS Appl. Mater. Interfaces 3 (2011). [3] P. Hale et al, Langmuir 24 (2008).

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Poster Abstract 10

Investigations on Glycol-Chitosan Particles for Vocal Fold Tissue Engineering Applications

Miral Toufaili1, Neda Latifi1, Meisam Asgari1, Rohit Gopinath3, Luc Mongeau1 1McGill University, Department of Mechanical Engineering, Canada, 2McGill University, Faculty of

Science, 3McGill University, Faculty of Science, Canada

Chitosan-based nano- and micro- particles have been previously investigated for drug delivery applications targeting various tissues. However, their potential use for vocal fold engineering has not yet been explored. The present work investigates the use of cross-linked glycol-chitosan particles for vocal fold engineering. Here, different groups of glycol-chitosan particles are fabricated which differ in their concentrations of the crosslinking agent, glyoxal, as well as the organic solution the particles are fabricated in. The particles are then characterized in terms of their size and morphology to find the most optimal group for vocal fold engineering. Four groups of particles were then selected for further investigations. These were fabricated using glycol-chitosan 4% and two different glyoxal concentrations of 0.5 % or 0.2 %. The particles were fabricated in two different organic solutions, and then washed vigorously. The morphologies of the particles were viewed using an AFM and LSM 710 Confocal Microscope. The ideal particles should have a spherical structure with a diameter of 0.5-3 mm. From the results obtained thus far, glycol-chitosan hydrogels seem poised to be used in repairing and regenerating human vocal fold tissue.

32


Poster Abstract 11

Development of Nanostructured Thin Films for Solar and Biomedical Applications

Natalia Milaniak1,3, Paul Brunet2,3, Francoise Massines3, Gaétan Laroche1 1Universite Laval, 2INRS-Institut Armand-Frappier, 3PROMES CNRS, Perpignan FRANCE

Introduction: The aim of this study is to develop a method to control the introduction of nanoparticles (NPs) in a thin film in order to create new materials with specifically tailored properties. These materials have the application in solar energy conversion as well as show promise in biomedicine. They are being obtained by AP-PECVD (Atmospheric Pressure-Plasma Enhanced Chemical Vapor Deposition). A gaseous or liquid precursor is injected into plasma generated by a dielectric barrier discharge (DBD). The low temperature plasma activates the precursor which accumulates at the surface to form the thin film. If the NPs and the liquid are simultaneously introduced into the plasma, a thin nanocomposite film is deposited. Methods: To control the morphology of the composite, two sinusoidal voltages of different frequencies must be alternated on a short time scale compared to the residence time of the gas in the plasma. This alternation is obtained via a double modulation. The lower frequency (LF) controls the transport of NPs to the surface and the higher frequency (HF) controls the growth of the thin film – polymer matrix. In order to better understand the process, a detailed study is carried out on the NPs in flight in the plasma and those incorporated in the matrix. The nanocomposites are analyzed by Fourier Transform Infrared Spectroscopy (FTIR) as well as Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and the chemical contribution of elements is determined by Energy-dispersive X-ray spectroscopy (EDS). The chemical composition of the plasma is characterized by space-resolved FTIR. To improve the sensitivity of the measurements, ethyl lactate (EL) which has seven absorption bands in the IR and silica nanoparticles (NPs) have been chosen as precursors for the nanocomposite. Different ratios of Duty Cycle (DC) have been studied and analyzed. Infrared analysis of plasma is correlated with the analysis of the chemical composition and the morphology of the thin film. Results and discussion: Nanocomposites have been produced using FSK in plasma filamentary regime. The neccesity to utilize both high frequency and low frequency for efficient deposition has been confirmed. SEM and AFM images have shown that for transporting NPs down to the substrate lower frequencies are needed. Lower the frequency, greater the amount of NPs on the substrate. Furthermore a dependency of required frequency and size of the nanoparticles has been observed: smaller the NP size higher frequency can be used for their deposition. FTIR and EDS of the deposition have revealed the presence of ethyl lactate in all of the samples. Nevertheless it has been confirmed that higher the plasma excitation frequency, higher the decomposition rate inside the discharge, hence bigger contribution of ethyl lactate in the sample. Conclusion: Significant differences in growth rate, chemical composition and ratio of NPs to polymer matrix are observed depending on the DC. In accordance to desired properties of the nanocomposite an adequate set of parameters can be found. This study shows that AP-PECVD has the potential to create nanocomposites with tailored properties for biomedical and solar applications.

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Poster Abstract 12

Greffage de la Fibronectine et du Peptide RGD sur des Prothèses en Titane pour Favoriser l’Adhésion des Cellules Épithéliales

Nawel Ghribi, Souhaila Ghadhab

Laboratoire d’ingénierie de surface, Centre de recherche de CHU de Québec – Université Laval, Hôpital Saint-François d’Assise et département de génie des mines, de la métallurgie et des

matériaux, Pavillon Adrien-Pouliot

Les prothèses transcutanées intra-osseuses (ITAP) représentent une alternative prometteuse par rapport aux prothèses orthopédiques externes puisqu’elles pourront diminuer grandement la douleur chez les patients. Par contre, l’infection constitue une grande complication en chirurgie orthopédique. Le but de ce projet de recherche est donc de promouvoir l’adhésion des cellules de la peau sur une prothèse en titane, ce qui permettrait de sceller la partie de l’implant qui sort de l’os et ainsi limiter l’infection(1). Dans le cadre de ces travaux, deux approches ont été établies. La première stratégie consiste à greffer la fibronectine et la deuxième à greffer le peptide RGD, qui correspond au site d’adhésion cellulaire de cette protéine(2, 3). Pour ce faire, nous avons procédé à la fonctionnalisation de la surface du titane par des phosphonates pour permettre le greffage covalent soit de la fibronectine, soit du peptide RGD(4) (5). Dans une deuxième partie, nous avons évalué l’adhésion, la prolifération et la viabilité des cellules de la peau sur ces surfaces modifiées. Les résultats préliminaires obtenus avec la fibronectine montrent que les phosphonates et la protéine ont été greffés de façon stable sur les substrats en titane. De plus, les surfaces comportant de la fibronectine greffée permettent une meilleure adhésion et prolifération des fibroblastes que celles avec de la fibronectine adsorbée. Ces résultats démontrent donc l’importance de greffer de façon covalente la fibronectine sur le substrat en titane afin de favoriser une meilleure interaction titane-tissu. References: 1.Pendegrass CJ, Gordon D, Middleton CA, Sun SNM, Blunn GW. Sealing the skin barrier around transcutaneous implants: in vitro study of keratinocyte proliferation and adhesion in response to surface modifications of titanium alloy. The Journal of bone and joint surgery British volume. 2008;90(1):114. 2.Valencia-Serna J, Chevallier P, Kc RB, Laroche G, Uludağ H. Fibronectin-modified surfaces for evaluating the influence of cell adhesion on sensitivity of leukemic cells to siRNA nanoparticles. Nanomedicine (London, England). 2016;11(9):1123. 3.Vallières K, Petitclerc É, Laroche G. Covalent Grafting of Fibronectin onto Plasma-Treated PTFE: Influence of the Conjugation Strategy on Fibronectin Biological Activity. Macromolecular Bioscience. 2007;7(5):738-45. 4.Tîlmaciu C-M, Mathieu M, Lavigne J-P, Toupet K, Guerrero G, Ponche A, et al. In vitro and in vivo characterization of antibacterial activity and biocompatibility: A study on silver-containing phosphonate monolayers on titanium. Acta Biomaterialia. 2015;15:266-77. 5. Bellis SL. Advantages of RGD peptides for directing cell association with biomaterials. Biomaterials. 2011;32(18):4205-10.

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Poster Abstract 13

A Novel Injectable Biomaterial for Vocal Fold Tissue Engineering

Neda Latifi, Meisam Asgari, Luc Mongeau

Department of Mechanical Engineering, McGill University

Injectable biomaterials with tissue-mimetic chemical composition and microstructure play an important role in vocal fold tissue engineering. In general, injectable biomaterials should be biocompatible and biodegradable, and provide a tissue-mimetic microenvironment. The vocal fold-specific biomaterials should also be mechanically stable under dynamic mechanical stimulations involved in phonation. Biomaterials containing collagen I and chitosan have been studied for various soft tissues. However, their potential use for vocal fold engineering has been overlooked. Long-term exposure to collagen I containing biomaterials was previously shown to increase scar formation. Collagen III is known to modulate scar formation, and has been reported to significantly decrease in scarred tissue. In the present study, we proposed a novel injectable tissue-mimetic biomaterial composed of heterotypic collagen fibrils of both collagen types I and III in glycol-chitosan [1]. The proposed biomaterial has a micro-fibrillar porous structure. The presence of collagen fibrils yields extracellular matrix-mimicking microenvironment to investigate the interactions between cells and the macromolecular components and morphometric parameters of the scaffold. Also, this can be used as a potential scaffold to fabricate engineered implants inside tissue culture bioreactors. Collagen I/glycol-chitosan and bulk glycol-chitosan hydrogels were used as positive and negative controls, respectively. The hydrogels were characterized using atomic force microscopy, scanning electron microscopy, and micro-computed tomography for their morphological properties. The swelling capacity, biochemical and mechanical stabilities as well as cell-scaffold interactions, viability, proliferation, cell adhesion and cell morphology were also studied. The proposed hydrogel was shown to support cell adhesion and provide longer half-life compared with hyaluronic acid-based counterparts commercially used for vocal fold engineering. This may thus decrease the need for regular reinjections currently performed for voice recovery. The proposed injectable biomaterial therefore combine the enhanced biochemical and biomechanical stability of a recent bulk glycol-chitosan hydrogel [2] with the cell adhesion characteristic of both collagen types I and III, and the role of collagen III in preventing scar formation. The proposed hydrogel could be a promising candidate for engineering mechanically active soft tissues such as heart valves and vocal folds. References: 1. Asgari, M., N. Latifi, H.K. Heris, H. Vali, and L. Mongeau, In vitro fibrillogenesis of tropocollagen type III in collagen type I affects its relative fibrillar topology and mechanics. Scientific Reports, Accepted. DOI: 10.1038/s41598-017-01476-y 2. Heris, H.K., N. Latifi, H. Vali, N. Li, and L. Mongeau, Investigation of Chitosan-glycol/glyoxal as an Injectable Biomaterial for Vocal Fold Tissue Engineering. Procedia Engineering, 2015. 110: p. 143-150.

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Poster Abstract 14

Low Temperature Plasma-Based Processes for Innovative Textiles

Pascale Chevallier, Ranna Toluei, Stéphane Turgeon, Lucie Lévesque, Diego Mantovani

CR-CHU de Québec - Université Laval, Laboratoire de biomatérieux et bioingénierie

Recently, there has been a strong interest in providing fabrics with improved properties: for example, greater wearing comfort while remaining fresh and odor free, waterproofing, ease-of cleaning, abrasion resistance or even antimicrobial properties. The innovative combination of controllable topographical and chemical modifications of the material will be a step forward for surface engineering towards real life application: to make surfaces less liable to microbial adhesion, or easier to be cleaned, with the addition of an antimicrobial agent. Fabric surfaces are not only exposed to abrasion and wear caused by daily contacts, but also to aggressive laundry procedures. So far, many different methods have been studied using approaches such as polymeric grafting or polymeric coating but usually lack stability. Higher mechanical and chemical stabilities are mandatory properties for such materials and need to be taken into consideration early during the design process. Using plasma-based process techniques, thereby obtaining highly stable and homogenous functional surfaces could be a promising alternative. In this work, original approaches based on plasma processes, as a highly powerful approach to modify textiles, therefore adding value, were investigated in order to enhance surface properties for textiles. For instance, different strategies were investigated (1) improving textile dyeability by rendering them more hydrophilic (2) improving textile resistance to abrasion by amorphous carbon based (a-C:H) thin films; and (3) combining with antibacterial activity, by adding silver during the plasma deposition process (a-C:H/Ag). The different plasma strategies have been tested on cotton and polyester (PET) fabrics. The efficiencies of the modifications were assessed by XPS, contact angle, SEM analyses and also by different screened tests depending on the targeted application. The results demonstrated that the plasma processes have permitted to modify the wetting behaviour, leading to an improvement of fabric dyeability, also to obtain adherent antibacterial nanocoating stable even after several laundry cycles. Thus, plasma processes are an effective platform for generating surface modifications in textiles, leading to high added value products. Besides, they can be applied by the textile industry using ecofriendly and non-toxic agents and processes.

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Poster Abstract 15

Oxide Layer Optimization and Direct Plasma Amination of L605 Alloy for its Application in Cardiovascular Devices.

Sergio Diaz-Rodriguez, Pascale Chevallier, Carlo Paternoster, Diego Mantovani

CR-CHU de Québec - Université Laval

Introduction: Cardiovascular diseases represent a leading cause of death in the world. Among them is atherosclerosis that characterizes for creating a narrowing plaque in the arteries, blocking the blood flow and leading to heart strokes. Once the atherosclerotic plaque has been formed, clinical intervention is needed. Stents are cardiovascular devices implanted in the damaged zone and support the artery from collapsing. Complications post-implantation persist and the risk of the regeneration of the atherosclerotic plaque is present, therefore the enhancing the biocompatibility is needed. Polymeric-coatings to graft molecules with biological activity is a common strategy but the lack of adhesion and integration leads to cracks and delamination on the coatings. Therefore, the need of a stable oxide layer resistant to deformation after implantation and that avoids the release of toxic ions is desired. Methods: In this work, three different surface treatments on L605 that allow the grafting of bioactive molecules on bare metallic L605 surface were studied to find the most suitable oxide layer for stents application: Electropolishing (EP), Thermal treatment (TT) and Plasma Immersion Ion Implantation of Oxygen (PIII). L605 previously cleaned were electropolished to remove impurities from the as received alloy. EP samples were used on further treatments; for TT samples, were placed in an air furnace at three different temperatures and two duration times; for PIII, samples were treated with oxygen in three different power input and two different times. Deformation tests were performed to select the treatments without cracks nor delamination: 400 C during 1 h for TT and -0.01 eV during 1 h for PIII. Characterization was performed using XPS, SEM, AFM, CA and ToF-SIMS. Results and discussion: Chemical composition, obtained by XPS and depth analyses confirmed the following: EP consisting of a thin chromium oxide layer, PIII with a cobalt oxide layer followed by a chromium oxide layer and TT with a thick oxide layer of both metals. Potentiodynamic tests revealed that the less corroded surface treatment was EP followed by PIII and TT. Plasma functionalization of the different oxide layers was performed using a Microwave Plasma fed with N2/H2 in a two-step procedure. The nitrogen detected by XPS analyses came from different species, chemical derivatization was performed to confirm the amine groups, which are functional groups that allow the further grafting of molecules on the surface. It was found that the EP sample had the best efficiency on the amination procedure (%NH2/N). Another way to confirm that the amination was successful was the change of contact angle in all surface treatments, changing from an hydrophobic behaviour to a significant more hydrophilic surface. Conclusion: In conclusion, bare metal samples were successfully functionalized with amine groups using MW plasma treatments, as evidenced by chemical derivatization, also EP was the surface treatment that was the most efficient in amination and corrosion resistant. Further experiments are required to assess the biocompatibility of this surface treatment and to enhance the biological activity by grafting molecules.

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Poster Abstract 16

Cellularized Collagen-Chitosane Biomaterial Used as a Model for the Studying of the Glycation on Wound Healing

Thiéry De Serres-Bérard, Sabrina Bellenfant, Francois Berthod

Universite Laval

Introduction: Skin wound healing is severely compromised in patients with diabetes and can lead to ulcer formation requiring lower limb amputation. Hyperglycemia promotes the formation of advanced glycation end-products (AGEs). AGEs are toxic for cells and have deleterious effects on wound healing. It was found recently that AGEs could inhibit reepithelialization by a direct effect on keratinocytes. Furthermore, ulcer formation often originates in lower limb from neuropathy-induced loss of pain and tactile sense. Skin denervation may compromise wound healing by reducing neurogenic inflammation. Since neuropeptides released during neurogenic inflammation can enhance keratinocytes proliferation and migration, neuropathy can also directly impair epidermal reparation. We believe that the combination of the deleterious effects of AGEs on epidermal self-repair capacity and the lack of neuropeptides in the skin induced by neuropathy contribute to the formation of persistent ulcers in diabetic patients. The aim of our project is to assess in vitro the influence of both AGEs and a treatment with AGEs inhibitor or neuropeptides on the reepithelialization process by keratinocytes. Methods: We have developed a biomaterial composed of bovine collagen and chitosan on which we seed cells like fibroblasts, endothelial cells and keratinocytes in order to produce an endothelialized tissue-engineered skin model. Then, we performed an 8 mm diameter wound in the reconstructed skin to follow the reepithelialization process. To determine the effects of glycation on wound healing, we treated the reconstructed skin with glyoxal, which promote quickly AGEs formation. Then, we attempted to enhance glycated-wound healing by treating the model with an anti-AGE molecule like aminoguanidine or an AGE-breaker like alagebrium. We also treated the model with neuropeptides secreted during neurogenic inflammation like the calcitonine-gene related peptide (CGRP) and substance P. Results and discussion: Results suggest that a treatment with glyoxal successfully induced AGE formation in the skin model and altered the histological aspect of the epidermis, reducing the rate of wound healing. A treatment with aminoguanidine reduced the level of glycation in the reconstructed skin and restored an healthy aspect of the epidermis while substance P and CGRP enhanced wound healing. Conclusion: The topical application of aminoguanidine, subtance P, and CGRP on ulcers may be a valuable approach to improve wound healing in diabetic patients. This biomaterial also offers the possibility to incorporate neurons and immune cells in the reconstructed skin, offering a unique tool to investigate the complex mecanisms of chronic diabetic wound.

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Poster Abstract 17

Proprieties of Chitosan-Xanthan Based Membranes for Orthopedical Applications

Cristiano Rodrigues1,2, Fernanda Bombaldi de Souza1,3, Renata Bombaldi de Souza3, Ângela Maria Moraes3, Márcia Rosângela Wink2, Diego Mantovani1

1Université Laval, Québec city, Canada, 2Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil, 3UNICAMP, São Paulo, Brazil

Introduction: many diseases and fractures may affect the bone tissue, resulting in structural defects and reduction of locomotion. Conventional therapies are sometimes inefficient when trying to enhance a correct tissue reparation in cases of large defects and when working with patients of an advanced age. Tissue engineered scaffolds are able to mimic the periosteum, a membrane present in the bone tissue which is fundamental in the healing process. Natural polymers such as chitosan are widely used to produce scaffolds because they are highly biocompatible and biodegradable. Xanthan gum is a polysaccharide that may interact with chitosan, resulting in complexes with improved properties. After the development of a scaffold for tissue replacement, it is necessary to verify its level of toxicity and to access its degradation through mechanical tests. A first screening can be done by subjecting the materials to direct or indirect contact over cell cultures at laboratory. Primary fibroblasts may be good candidates to access the viability after exposure because they are one of the main constituents of the periosteum. In addition, osteoblasts follow as another cell type that would be directly affected with the degradation products of this graft, making it also interesting for this type of verification. Methods: four different associations were developed and proposed by a research group coordinated by Prof. Àngela Moraes from UNICAMP, São Paulo, Brazil. Chitosan-xanthan scaffolds containing or not Silpuran® 2130 A/B (10% v/v) or Kolliphor® P188 (10% or 25% w/w) were already produced and characterized regarding their visual aspect, morphology, thickness, mechanical properties (hydration and degradation levels), and biological performance (indirect cytotoxicity to human primary fibroblasts (HDF) and a cell lineage of human osteosarcoma (Saos-2)). Briefly, extracts with the membranes were conditioned with its degradation products for 24 h using culture media specific for each cell line, following a ratio of 0.01 g / mL, as regulated by ISO 10993-5. The extracts were used as treatment of the two lines during 24 hours. After, the Alamar Blue (Resazurin soudium salt R7017 SIGMA) was used as an indicator of metabolic function and cellular health. The cells were still observed and compared with the controls by optical phase contrast microscopy. Results & discussion: Membranes demonstrated a complete level of hydration in 24 hours and showed no degradation levels for one week. Immortalized osteoblasts and primary fibroblasts did not show morphological differences, comparing controls with cells exposed indirectly to the membranes. Cytotoxicity results demonstrated that membranes are likely to maintain cell viability of both types, showing a slight increase in membranes in which chitosan underwent a phosphorylation process, but without statistical significance (One-way ANOVA). Conclusion: the previous results suggest the potential use of this polysaccharide association as biomaterial for periosteum replacement in bone diseases and lesions. However, further studies are needed to verify the safety of a long-term application, as well as the rate of degradation in a physiological place.

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Poster Abstract 18

Interaction of Red Blood Cells and Platelets with Fe-Mn-Ag Alloy

Pedram Sotoudehbagha 1, 2, Mehrdad Khakbiz 1, Saeed Sheibani 3, Hendra Hermawan 2 1Division of Biomedical Engineering, Department of Life Science Engineering, Faculty of New Sciences

and Technologies, University of Tehran, Tehran, Iran. 2Department of Mining, Metallurgical and Materials Engineering & CHU de Quebec Research Center, Laval University, Quebec City, Canada.

3School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, Tehran, Iran.

Biodegradable metals can be the next generation of implants which degraded in body after healing procedure were completed without implant residues [1]. As a result, they can avoid second surgery to remove implants or avoid in-stent restenosis. Emerging of blood compatible implants, especially cardiovascular stent, motivated researchers to evaluate blood compatibility of these materials. Biodegradable Fe based alloys are one of the candidate to be used as the stent. One major challenge for Fe based biodegradable alloys is controlling degradation rate in vivo. Thus, Ag as a noble metal added to Fe-Mn alloy to accelerate corrosion rate. However, there can be concerns about the interaction of Ag to blood cells and platelet adhesion. Ion release can affect red blood cells (RBC), platelet adhesion, cell metabolic activity, etc. Interaction of red blood cells (RBC) with biomaterials or with a biomaterial extract can cause the release of intracellular hemoglobin (hemolysis) [2]. Platelet activation is one of the major steps of blood thrombogenesis that should be avoided on biomaterial in contact to the blood [3]. In this study Fe-Mn-Ag alloys synthesized by mechanical alloying and subsequent sintering. Then to evaluate hemolysis and coagulation, samples were incubated in whole blood and platelet-rich plasma (PRP). Results showed that Ag addition up to 1 wt. % can both inhibit platelet adhesion and its hemolysis is less than 5% which is considered as blood compatible material. [1] Y. F. Zheng, X. N. Gu, and F. Witte, “Biodegradable metals,” Mater. Sci. Eng. R Reports, vol. 77, pp.

1–34, 2014. [2] S. Henkelman, G. Rakhorst, J. Blanton, and W. van Oeveren, “Standardization of incubation

conditions for hemolysis testing of biomaterials,” Mater. Sci. Eng. C, vol. 29, no. 5, pp. 1650–1654, 2009.

[3] E. Zhang, H. Chen, and F. Shen, “Biocorrosion properties and blood and cell compatibility of pure iron as a biodegradable biomaterial,” J. Mater. Sci. Mater. Med., vol. 21, no. 7, pp. 2151–2163, Jul. 2010.

[4] F756-08 A. Standard Practice for Assessment of Hemolytic Properties of Materials. West Conshohocken, PA, USA: ASTM International; 2000.

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