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Multifunctional regenerative conduits for peripheral nerve repair

English title Multifunctional regenerative conduits for peripheral nerve repair
Applicant Lacour Stéphanie
Number 149609
Funding scheme Interdisciplinary projects
Research institution Laboratoire des interfaces bioélectroniques flexibles EPFL - STI - IMT - LSBI
Institution of higher education EPF Lausanne - EPFL
Main discipline Material Sciences
Start/End 01.10.2013 - 31.03.2017
Approved amount 460'350.00
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All Disciplines (2)

Discipline
Material Sciences
Neurophysiology and Brain Research

Keywords (4)

peripheral nerve; cell therapy; microelectrodes; regenerative conduits

Lay Summary (French)

Lead
Réparation fonctionnelle du nerf périphérique à l'aide de microconduits multifonctionels
Lay summary

Les nerfs périphériques relient le cerveau et la moelle épinière à l'ensemble du corps humain. Ils contrôlent les fonctions de mouvement, la sensation et la coordination. Lorsque ces longues structures sont endommagées, la communication entre le cerveau, la moelle épinière et les muscles, organes ou peau, est altérée ou interrompue. Une réparation chirurgicale du nerf est souvent requise, mais la récupération fonctionnelle après la lésion du nerf périphérique est rarement atteinte, surtout si une longue portion du nerf doit être enlevée. 

Le projet explorera la réparation du nerf périphérique à l’aide de conduits de régénération artificiels. Trois stratégies issues de l’ingénierie seront évaluées individuellement et combinées, en direction d’une réparation fonctionnelle du nerf: (1) la thérapie cellulaire, (2) l’implémentation de matériaux polymers aux propriétés mécaniques adaptées aux tissus biologiques, et (3) la stimulation électrique in situ des neurons régénérants.

Direct link to Lay Summary Last update: 09.10.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
A microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers
Gribi Sandra, du Bois de Dunilac Sophie, Ghezzi Diego, Lacour Stéphanie P. (2018), A microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers, in Nature Communications, 9(1), 4403-4403.
In vitro evaluation of gel-encapsulated adipose derived stem cells: biochemical cues for in vivo peripheral nerve repair
de Luca Alba (2018), In vitro evaluation of gel-encapsulated adipose derived stem cells: biochemical cues for in vivo peripheral nerve repair, in Journal of Tissue Engineering and Regenerative Medicine (JTERM), 12(3), 676-686.
Controlled Sub‐Micrometer Hierarchical Textures Engineered in Polymeric Fi-bers and Microchannels via Thermal Drawing
Nguyen-Dang Tung (2017), Controlled Sub‐Micrometer Hierarchical Textures Engineered in Polymeric Fi-bers and Microchannels via Thermal Drawing, in Advanced Functional Materials, 27(10), 1605935-1-1605935-11.
Chronic Electrical Nerve Stimulation as a Therapeutic Intervention for Peripheral Nerve Repair.
Sakuma Miyuki (2015), Chronic Electrical Nerve Stimulation as a Therapeutic Intervention for Peripheral Nerve Repair., in Bioelectronic Medicine, (2), 43-48.
Tissue engineered constructs for peripheral nerve repair: current research concepts and future perspectives.
de Luca Alba (2015), Tissue engineered constructs for peripheral nerve repair: current research concepts and future perspectives., in Plastic and Aesthetic Research (PAR) journal, 2(4), 213-219.
Extracellular matric components in peripheral nerve repair: how to affect neural cellular response and nerve regeneration?
de Luca Alba (2014), Extracellular matric components in peripheral nerve repair: how to affect neural cellular response and nerve regeneration?, in Neural Renegeration Research, 9(22), 1943-1948.

Collaboration

Group / person Country
Types of collaboration
CHUV Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
EURAPS Research Council Talk given at a conference Encapsulation of adipose-derived stem cells (ASC) in degradable gels for peripheral nerve repair and neuroprosthetic devices. 24.05.2017 Pisa, Italy De Luca Alba; Lacour Stéphanie; Raffoul Wassim;
Center of MicroNano Technology (CMI) day 2017 - EPFL Poster Nerve-on-a-chip for high resolution recording 02.05.2017 Lausanne, Switzerland Lacour Stéphanie; Gribi Sandra;
Bioengineering Day 2016 - EPFL Poster Nerve-on-a-chip with high recording performance: From compound nerve action potential to single-fiber action potential 28.09.2016 Lausanne, Switzerland Gribi Sandra; Lacour Stéphanie;
52nd Congres de la societe Suisse de chirurgie plastique, reconstructive et esthetique (SSCPRE) Talk given at a conference Encapsulation of adipose-derived stem cells (ASC) in degradable gels for peripheral nerve repair and neuroprosthetic devices. 09.09.2016 Lausanne, Switzerland di Summa Pietro; De Luca Alba; Raffoul Wassim; Lacour Stéphanie;
Center of MicroNano Technology (CMI) day 2016 - EPFL Poster PDMS regenerative Peripheral Nerve interfaces, 03.05.2016 Lausanne, Switzerland Gribi Sandra; De Luca Alba; Lacour Stéphanie;
Materials Research Society Fall Meeting, symposium D Individual talk D-Biological and Bioinspired Materi-als in Photonics and Electronics—Biology, Chemistry and Physics 29.11.2015 Boston, United States of America De Luca Alba; Lacour Stéphanie;
4th TERMIS World Congress Poster Fibrin Gels as Degradable Matrices for Adipose Stem Cells Encapsulation in Peripheral Nerve Repair. 08.09.2015 Boston, United States of America Raffoul Wassim; di Summa Pietro; Lacour Stéphanie; De Luca Alba;
Center of MicroNanoTechnology (CMI) day 2015 - EPFL Poster Regenerative microchannel implant nerve interface 10.02.2015 Lausanne, Switzerland Lacour Stéphanie; Gribi Sandra;
Neuroscience 2014 Talk given at a conference Chronic spike recordings from a regenerating peripheral nerve in awake and freely 15.11.2014 Washington D.C., United States of America di Summa Pietro; Lacour Stéphanie;
Swiss Institute of Cell Therapies (SICT) Second Scientific Meeting « Update on Cell Therapies Strategies at the different Swiss Centers: Focus on Regulatory Aspects” Talk given at a conference From the clinics to the lab. Adipose-derived stem cells: new perspectives to enhance nerve regeneration. 12.11.2014 Geneva, Switzerland di Summa Pietro;
50th Congres de la societe Suisse de chirurgie plastique, reconstructive et esthetique (SSCPRE) Poster A microchannel conduit for real-time and chronic study of a regenerating peripheral nerve. 05.09.2014 Geneva, Switzerland di Summa Pietro; Lacour Stéphanie;
International Symposium on Peripheral Nerve regeneration and repair Talk given at a conference PDMS microchannel regenerative peripheral nerve interface. 24.01.2014 Torino, Italy Lacour Stéphanie; di Summa Pietro;


Awards

Title Year
Best student talk award price at 2017 MRS Spring Meeting, Phoenix, Arizona (17-22 April 2017) S Gribi, D Ghezzi, SP Lacour, (2017). A Nerve-on-a-Chip Platform to Facilitate the Design of Peripheral Nerve Interfaces. GBP 50.- voucher/ book gift from the Royal Society of Chemistry 2017

Associated projects

Number Title Start Funding scheme
157800 Soft bioelectronics for bidirectional neural implants 01.03.2016 SNSF Consolidator Grants

Abstract

Peripheral nerves are of crucial importance for the integrity of the body function since they are nec-essary for the transmission of motor impulses and for the perception of sensory stimula. When they are damaged following either a traumatic injury or degenerative disease, motor functions as well as sensory perception are impaired. Functional recovery is thus the main goal of therapeutic interven-tion in peripheral nerve repair. However, peripheral nerve injuries remain a challenge for recon-structive surgeons. Nerve grafting and tubulization techniques are the most frequent clinical approaches to repair a damaged nerve but they rarely lead to satisfactory functional recovery of the original limb functions, with persistence of numbness, disesthesia and functional impairment. Pe-ripheral nerve injury represents an important issue in medicine as patients with peripheral nerve trauma are often at the peak of their employment productivity and any loss or decrease of function is particularly devastating2.The proposed project aims at significantly improving the quality of peripheral nerve regeneration after traumatic injury using multifunctional, artificial regenerative conduits. The latter will be engi-neered so that their performance over a long gap at least matches that of autografts. Three neural engineering strategies will be assessed, individually and combined, towards nerve functional recov-ery: (1) cell therapy, (2) biocompatible materials and coatings with matched mechanical properties to the surrounding tissues, and (3) in situ electrical stimulation of the regenerating axons. The project vehicle will be a multiconduit regenerative implant, which architecture roughly mimics the peripheral nerve anatomy. The engineered nerve conduits will integrate one or several of the following features: regenerative cell transplantation (Primary Schwann cells and Schwann cell-like differentiated adipose-derived stem cells (dASC)), a controlled biomechanical microenvironment with wall and intra-conduit guidance cues, and electrical stimulation. Using rat-model sciatic nerve injury, we will systematically assess nerve recovery during each of the three phases of nerve repair: (i) axonal regeneration, (ii) target reinnervation, and (iii) complex func-tion recovery. We will evaluate whether the biomimetic and electrically active nerve conduits allow for increased regeneration of axons across the injury site and improved functional recovery. The project integrates a multidisciplinary team composed of engineers, and plastic and hand sur-geons, already working on complementary aspects of nerve reconstruction, biomaterials, neural electrodes and rehabilitation. Innovations produced in this project will open challenging and competitive applications in clinical nerve repair. We anticipate the project outcomes will become clinically viable tools for accelerating nerve fibers regeneration, muscle reinnervation thus high functional recovery.
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