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Tissue engineering and medical devices

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Biomaterials for tissue engineering

Hyperelastic and absorbable architected biomaterials dedicated to soft tissue reconstruction.

About the project:

This objective of this project is to combine selected degradable polymers and the electrospinning process to produce architected scaffolds to be used in soft tissue engineering. The prediction of the degradation rates, of the evolution of the scaffolds mechanical properties, and of the cells/scaffolds construct behaviour are also forseen.

Contact:

Xavier Garric
Xavier Garric
Benjamin Nottelet
Benjamin Nottelet
Coline Pinese
Coline Pinese
Audrey Bethry
Audrey Bethry
Stéphane Dejean
Stéphane Dejean

Students:

Christopher Yusef LEON-VALDIVIESO
Christopher Yusef LEON-VALDIVIESO

Collaborations:

Funding:

Laboratoire URGO

Long-term in vivo performances of polylactide / iron oxide nanoparticles core-shell fibrous nanocomposites as MRI-visible magneto-scaffolds

Biomat. Sci. XX, XXX–XXX (2021)

 Awada H., Seene S., Laurencin D., Lemaire L., Franconi F., Bernex F., Bethry A., Garric X., Guari Y., Nottelet B.

ABSTRACT

There is a growing interest in magnetic nanocomposites in biomaterials science. In particular, nanocomposites that combine poly(lactide) (PLA) nanofibers and super paramagnetic iron oxide nanoparticles (SPIONs), which can be obtained by either electrospinning of a SPIONs suspension in PLA or by precipitating SPIONs at the surface of PLA, are well documented in the literature. However, these two classical processes yield nanocomposites with altered materials properties, and their long-term in vivo fate and performances have in most cases only been evaluated over short periods of time. Recently, we reported a new strategy to prepare well-defined PLA@SPIONs nanofibers with a quasi-monolayer of SPIONs anchored at the surface of PLA electrospun fibers. Herein, we report on a 6-month in vivo rat implantation study with the aim of evaluating the long-term magnetic resonance imaging (MRI) properties of this new class of magnetic nanocomposites, as well as their tissue integration and degradation. Using clinically relevant T2-weighted MRI conditions, we show that the PLA@SPIONs nanocomposites are clearly visible up to 6 months. We also evaluate here by histological analyses the slow degradation of the PLA@SPIONs, as well as their biocompatibility. Overall, these results make these nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

Assessing the combination of magnetic field stimulation, iron oxide nanoparticles, and aligned electrospun fibers for promoting neurite outgrowth from dorsal root ganglia in vitro

Acta Biomaterialia 131, 302–313 (2021)

Funnell J.L., Ziemba A.M., Nowak J.F., Awada H., Prokopiou N., Samuel J., Guari Y., Nottelet B., Gilbert R.J.

ABSTRACT

Magnetic fiber composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and electrospun fibers have shown promise in tissue engineering fields. Controlled grafting of SPIONs to the fibers post-electrospinning generates biocompatible magnetic composites without altering desired fiber morphology. Here, for the first time, we assess the potential of SPION-grafted scaffolds combined with magnetic fields to promote neurite outgrowth by providing contact guidance from the aligned fibers and mechanical stimulation from the SPIONs in the magnetic field. Neurite outgrowth from primary rat dorsal root ganglia (DRG) was assessed from explants cultured on aligned control and SPION-grafted electrospun fibers as well as on non-grafted fibers with SPIONs dispersed in the culture media. To determine the optimal magnetic field stimulation to promote neurite outgrowth, we generated a static, alternating, and linearly moving magnet and simulated the magnetic flux density at different areas of the scaffold over time. The alternating magnetic field increased neurite length by 40% on control fibers compared to a static magnetic field. Additionally, stimulation with an alternating magnetic field resulted in a 30% increase in neurite length and 62% increase in neurite area on SPION-grafted fibers compared to DRG cultured on PLLA fibers with untethered SPIONs added to the culture media. These findings demonstrate that SPION-grafted fiber composites in combination with magnetic fields are more beneficial for stimulating neurite outgrowth on electrospun fibers than dispersed SPIONs.

Offre de CDD 1 an Ingénieur de Recherche – prestation industrielle

Poste d’ingénieur de recherche CDD 1 an: Caractérisation et déformulation d’un système de libération prolongée injectable

Le Département des Polymères pour la Santé est les Biomatériaux de l’IBMM souhaite recruter un Ingénieur de Recherche (<3 ans d’expérience) dans le cadre de la réalisation d’un contrat de prestation industrielle visant à caractériser et déformuler un système de libération prolongée injectable.

 

Contexte : Le Département des Polymères pour la Santé est les Biomatériaux de l’IBMM (https://ibmmpolymerbiomaterials.com/) souhaite recruter un Ingénieur de Recherche (<3 ans d’expérience) dans le cadre de la réalisation d’un contrat de prestation industrielle.

 

Mission principale : L’Ingénieur(e) de Recherche à recruter sera en charge d’une étude de déformulation d’un système de libération prolongée injectable fourni par l’entreprise mandante.

 

Activités : L’ingénieur(e) de Recherche sera amené à effectuer des analyses sur des formulations fournies par l’entreprise afin d’en identifier les composants. Suite à cette étape de déformulation, il(elle) devra synthétiser les composés identifiés et les utiliser pour préparer une formulation semblable à la formulation de référence. Cette formulation cible sera validée par l’entreprise mandante.

 

Compétences / qualifications : L’ingénieur de Recherche à recruter devra avoir de fortes compétences en analyse et caractérisation de formulations, en particulier contenant des polymères. Une expérience en synthèse macromoléculaire sera également la bienvenue. Les techniques d’analyse/caractérisation à maîtriser sont : chromatographie HPLC, chromatographie d’exclusion stérique (SEC), chromatographie préparative, spectroscopie de masse (en particulier Maldi-Tof), résonance magnétique nucléaire (RMN), calorimétrie différentielle (DSC), thermogravimétrie (TGA).

 

Date: début de contrat souhaité 1er septembre 2021

 

Responsable du projet : Prof. Benjamin Nottelet (benjamin.nottelet@umontpellier.fr)

 

Comment postuler : le(la) candidat(e) intéressé(e) doit faire parvenir au responsable du projet un CV détaillé, une lettre de motivation et le contact de 2 personnes référentes. Tout dossier non complet ne sera pas étudié.

 

Date limite de candidature : 30 juillet 2021.

 

 

Best practices in Regenerative Medicine

Save the date: next 23 June 2021  (from 10:00 to 11:15 am)

A seminar will be held on the Best practices in Regenerative Medicine

Link: https://unav.zoom.us/j/95703457456?pwd=VjNac1pUeklIM3owYmltK0lsNExqZz09
Meeting ID: 957 0345 7456
Passcode: 442924

best practice in regenerative medecine 2021

Jump to other drug delivery related subjects >>> Tissue engineering >>> Biomedical innovation

Medical devices:

Anti-adhesion degradable medical device

About the project:

We are working mainly on two axes:

Anti-adhesion, self expanding, degradable medical device for the prevention of intra-uterine adhesions.

Anti-adhesion and degradable medical device for the prevention of post-operative adhesions in orthopedic surgery

Contact:

Xavier Garric
Xavier Garric
Hélène Van Den Berghe
Hélène Van Den Berghe
Audrey Bethry
Audrey Bethry
Jean Coudane
Jean Coudane
Vincent Letouzey
Cédric Paniagua
Cédric Paniagua

Students:

Salomé Leprince
Stéphanie Huberlant
Lucie Allegre

Collaborations:

Service de Gynécologie Obstétrique (CHU Nîmes)

Pr Michel Chammas (Orthopaedic Surgery Service, CHU Montpellier)

Womed

 

Funding:

SATT AxLR, Région Occitanie, CHU Nîmes, Université de Montpellier

Algerian Government Excellence grant

A new bioabsorbable polymer film to prevent peritoneal adhesions validated in a post-surgical animal model

PLoS One 13, e0202285 (2018)

 Allegre, L., Le Teuff, I., Leprince, S., Warembourg, S., Taillades, H., Garric, X., Letouzey, V. & Huberlant, S.

ABSTRACT

Background – Peritoneal adhesions are a serious surgical postoperative complication. The aim of this study is to investigate, in a rat model, the anti-adhesive effects of a bioabsorbable film of polymer combining polyethylene glycol and polylactic acid that can be easily applied during surgery.

Materials and Methods – Sixty three animals were randomized into five groups according to the anti- adhesion treatment: Hyalobarrier®, Seprafilm®, Polymer A (PA), Polymer B (PB), and control. The rats were euthanized on days 5 and 12 to evaluate the extent, severity and degree of adhesions and histopathological changes. Three animals were euthanized at day 2 in PA, PB and control groups to observe the in vivo elimination.

Results  – Macroscopic adhesion formation was significantly lower in the PA group than in the control group at day 5 (median adhesion score 0±0 vs 9.6 ±0.5 p=0.002) and at day 12 (0±0 vs 7.3±4 p=0.02). Furthermore, median adhesion score at day 5 was significantly lower in the PA group than in the Seprafilm® group (0±0 vs 4.2± 3.9 p = 0.03). Residence time of PA seems longer than PB.

Conclusion – The PA bioabsorbable film seems efficient in preventing the formation of peritoneal adhesions

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Advanced wound dressings

About the project:

This project gathers different approaches towards original and/or advanced wound dressings. It is based on the combination of 1) degradable polymers exhibiting controlled degradation rates and mechanical properties, 2) chemical modifications and 3) 3D printing techniques or electrospinning to design innovative wound dressings.

Contact:

Xavier Garric
Xavier Garric
Hélène Van Den Berghe
Hélène Van Den Berghe
Coline Pinese
Coline Pinese
Benjamin Nottelet
Benjamin Nottelet
Audrey Bethry
Audrey Bethry

Students:

Christopher Yusef LEON-VALDIVIESO
Christopher Yusef LEON-VALDIVIESO
Coraline Chartier
Coraline Chartier

Collaborations:

Laboratoire URGO

Pr. Tatiana Budtova and Dr. Sytze Buwalda (CEMEF, Mines Paristech)

Funding:

CNRS interdisciplinary PhD program

Long-term in vivo performances of polylactide / iron oxide nanoparticles core-shell fibrous nanocomposites as MRI-visible magneto-scaffolds

Biomat. Sci. XX, XXX–XXX (2021)

 Awada H., Seene S., Laurencin D., Lemaire L., Franconi F., Bernex F., Bethry A., Garric X., Guari Y., Nottelet B.

ABSTRACT

There is a growing interest in magnetic nanocomposites in biomaterials science. In particular, nanocomposites that combine poly(lactide) (PLA) nanofibers and super paramagnetic iron oxide nanoparticles (SPIONs), which can be obtained by either electrospinning of a SPIONs suspension in PLA or by precipitating SPIONs at the surface of PLA, are well documented in the literature. However, these two classical processes yield nanocomposites with altered materials properties, and their long-term in vivo fate and performances have in most cases only been evaluated over short periods of time. Recently, we reported a new strategy to prepare well-defined PLA@SPIONs nanofibers with a quasi-monolayer of SPIONs anchored at the surface of PLA electrospun fibers. Herein, we report on a 6-month in vivo rat implantation study with the aim of evaluating the long-term magnetic resonance imaging (MRI) properties of this new class of magnetic nanocomposites, as well as their tissue integration and degradation. Using clinically relevant T2-weighted MRI conditions, we show that the PLA@SPIONs nanocomposites are clearly visible up to 6 months. We also evaluate here by histological analyses the slow degradation of the PLA@SPIONs, as well as their biocompatibility. Overall, these results make these nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

Assessing the combination of magnetic field stimulation, iron oxide nanoparticles, and aligned electrospun fibers for promoting neurite outgrowth from dorsal root ganglia in vitro

Acta Biomaterialia 131, 302–313 (2021)

Funnell J.L., Ziemba A.M., Nowak J.F., Awada H., Prokopiou N., Samuel J., Guari Y., Nottelet B., Gilbert R.J.

ABSTRACT

Magnetic fiber composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and electrospun fibers have shown promise in tissue engineering fields. Controlled grafting of SPIONs to the fibers post-electrospinning generates biocompatible magnetic composites without altering desired fiber morphology. Here, for the first time, we assess the potential of SPION-grafted scaffolds combined with magnetic fields to promote neurite outgrowth by providing contact guidance from the aligned fibers and mechanical stimulation from the SPIONs in the magnetic field. Neurite outgrowth from primary rat dorsal root ganglia (DRG) was assessed from explants cultured on aligned control and SPION-grafted electrospun fibers as well as on non-grafted fibers with SPIONs dispersed in the culture media. To determine the optimal magnetic field stimulation to promote neurite outgrowth, we generated a static, alternating, and linearly moving magnet and simulated the magnetic flux density at different areas of the scaffold over time. The alternating magnetic field increased neurite length by 40% on control fibers compared to a static magnetic field. Additionally, stimulation with an alternating magnetic field resulted in a 30% increase in neurite length and 62% increase in neurite area on SPION-grafted fibers compared to DRG cultured on PLLA fibers with untethered SPIONs added to the culture media. These findings demonstrate that SPION-grafted fiber composites in combination with magnetic fields are more beneficial for stimulating neurite outgrowth on electrospun fibers than dispersed SPIONs.

Offre de CDD 1 an Ingénieur de Recherche – prestation industrielle

Poste d’ingénieur de recherche CDD 1 an: Caractérisation et déformulation d’un système de libération prolongée injectable

Le Département des Polymères pour la Santé est les Biomatériaux de l’IBMM souhaite recruter un Ingénieur de Recherche (<3 ans d’expérience) dans le cadre de la réalisation d’un contrat de prestation industrielle visant à caractériser et déformuler un système de libération prolongée injectable.

 

Contexte : Le Département des Polymères pour la Santé est les Biomatériaux de l’IBMM (https://ibmmpolymerbiomaterials.com/) souhaite recruter un Ingénieur de Recherche (<3 ans d’expérience) dans le cadre de la réalisation d’un contrat de prestation industrielle.

 

Mission principale : L’Ingénieur(e) de Recherche à recruter sera en charge d’une étude de déformulation d’un système de libération prolongée injectable fourni par l’entreprise mandante.

 

Activités : L’ingénieur(e) de Recherche sera amené à effectuer des analyses sur des formulations fournies par l’entreprise afin d’en identifier les composants. Suite à cette étape de déformulation, il(elle) devra synthétiser les composés identifiés et les utiliser pour préparer une formulation semblable à la formulation de référence. Cette formulation cible sera validée par l’entreprise mandante.

 

Compétences / qualifications : L’ingénieur de Recherche à recruter devra avoir de fortes compétences en analyse et caractérisation de formulations, en particulier contenant des polymères. Une expérience en synthèse macromoléculaire sera également la bienvenue. Les techniques d’analyse/caractérisation à maîtriser sont : chromatographie HPLC, chromatographie d’exclusion stérique (SEC), chromatographie préparative, spectroscopie de masse (en particulier Maldi-Tof), résonance magnétique nucléaire (RMN), calorimétrie différentielle (DSC), thermogravimétrie (TGA).

 

Date: début de contrat souhaité 1er septembre 2021

 

Responsable du projet : Prof. Benjamin Nottelet (benjamin.nottelet@umontpellier.fr)

 

Comment postuler : le(la) candidat(e) intéressé(e) doit faire parvenir au responsable du projet un CV détaillé, une lettre de motivation et le contact de 2 personnes référentes. Tout dossier non complet ne sera pas étudié.

 

Date limite de candidature : 30 juillet 2021.

 

 

Best practices in Regenerative Medicine

Save the date: next 23 June 2021  (from 10:00 to 11:15 am)

A seminar will be held on the Best practices in Regenerative Medicine

Link: https://unav.zoom.us/j/95703457456?pwd=VjNac1pUeklIM3owYmltK0lsNExqZz09
Meeting ID: 957 0345 7456
Passcode: 442924

best practice in regenerative medecine 2021

Flux Polymers develops antibacterial coatings for plastics based on a technology developed at PHBM by Benjamin Nottelet and Anita Luxenhofer and patented with SATT AxLR

Bacterial infection is a leading cause of therapeutic failure for medical devices. To overcome this Benjamin Nottelet and Anita Luxenhofer developped few years ago a technology allowing for the direct anchoring of antibacterial polymers on most polymeric surfaces. This work, initially funded by the University of Montpellier and Campus France led to two publications (https://doi.org/10.1002/adfm.201800976 ; https://doi.org/10.1016/j.msec.2020.110811) and was patented by SATT Axlr (WO2017220804A1). Today this technology has found its way thanks to a strong determination from the company Flux Polymers that received seed funding from the family office Förster & Franke consulted Investors! Congratulations
Flux Polymers produces a hydrophilic polymer that can be spray or dip coated onto plastic surfaces and permanently linked by UV-light. The patented coating prevents the attachment and growth of bacteria. The antibacterial effect of the coating is purely based on a physical effect, so that no toxic substances are released that could cause resistance in bacteria. The process is fast, cost efficient and not detrimental to the used material.

Well-defined polyester-grafted silica nanoparticles for biomedical applications: Synthesis and quantitative characterization

Polymer, 2020, 211, 123048

Lagarrigue P., Soulié J., Grossin D., Dupret-Bories A., Combes C., Darcos V.

ABSTRACT

Polyester-based composites with silica nanoparticles fillers are promising candidates as biomaterials due to improved mechanical and biological properties. However, nanofillers use generally leads to an inhomogeneous distribution inside the polymer matrix because of agglomeration, decreasing composites overall performances. To improve nanofillers dispersion, the aim of this study is to prepare and characterize poly(D,L lactide) grafted silica nanoparticles using “grafting to” method and to quantify the amount of grafted poly(D,L lactide). Firstly, well-defined N hydroxysuccinimide ester poly(D,L lactide)s were synthetized through a new pathway. Then, amino-functionalized silica nanoparticles were grafted with those customized polyesters yielding an amide covalent bond between both reagents. Such PDLLA grafted nanoparticles were precisely characterized and the grafting amount was quantified using a dual approach based on TGA and FTIR analysis. The synthesis and the characterization methods developed constitute a robust and reproducible way to design well-defined polymer grafted silica nanoparticles that could be used as nanofillers in polymer matrix nanocomposites for biomedical

NANOCOMPOSITES

Prescillia Lagarrigue’s PhD explained in 5 minutes

Offre de position post-doctorale « Projet DECAP, Hydrogels pour la décontamination corporelle d’actinides à base de polymères biocompatibles »

Offre de position post-doctorale

« Projet DECAP, Hydrogels pour la décontamination corporelle d’actinides à base de polymères biocompatibles »

Montpellier France

Laboratoire d’accueil : Département « Biopolymères Artificiels », Institut des Biomolécules Max Mousseron (UMR 5247), Université de Montpellier, France

Durée du projet : 8 mois

Date de début du contrat souhaité : février/mars 2021

Financement : ANR

 

Projet :

Le projet DECAP concerne le développement d’hydrogels à base de polymères originaux en vue de la décontamination corporelle externe d’actinides. L’objectif est de synthétiser et de formuler sous forme d’hydrogel de nouveaux polymères chélatants de radionucléides. La mise au point de ces systèmes à base de polymères sera réalisée selon un cahier des charges précis. Ce projet pluridisciplinaire va de la synthèse et la polymérisation de monomères fonctionnels à l’étude biologique des formulations, en passant par les études des propriétés de complexation. Dans ce cadre, un consortium pluridisciplinaire a été élaboré associant l’Institut des Biomolécules Max Mousseron (IBMM) et l’Institut Charles Gerhardt (ICG) de Montpellier, l’Institut de Chimie Séparative de Marcoule (ICSM) et Institut Galien Paris-Sud (IGPS). Le candidat devra faire le lien entre les différentes équipes impliquées.

Des détails supplémentaires seront donnés aux candidats intéressés par ce projet.

 

Profil du candidat recherché :

Le(la) candidat(e) devra être titulaire d’un doctorat en chimie organique ou en chimie des polymères. Il(elle) devra posséder de solides compétences en chimie organique et/ou macromoléculaire. Une expérience dans le domaine des procédés de séparation et/ou sorption serait un plus. Il(elle) devra avoir le goût pour aborder un sujet de recherche expérimental et pluridisciplinaire. Il(elle) devra avoir d’excellentes capacités pour le travail en équipe et être à l’aise dans la communication. Il(elle) devra faire preuve d’autonomie dans son organisation et d’esprit d’initiative.

Modalités de candidature :

Merci de postuler obligatoirement sur le site emploi.cnrs.fr (Référence UMR5247-MORJOL-007) et d’envoyer votre CV et votre lettre de motivation par courrier électronique à Vincent DARCOS et à Sophie MONGE-DARCOS au plus tard le 18 janvier 2021 minuit.

Emails : vincent.darcos@umontpellier.fr et sophie.monge-darcos@umontpellier.fr

Implantable medical devices for soft tissues

About the project:

We design polymers to improve or create new implants in the field of soft tissue regeneration (ligament prosthesis, hernia…)

Contact:

Xavier Garric
Xavier Garric
Benjamin Nottelet
Benjamin Nottelet
Jean Coudane
Jean Coudane

Students:

Collaborations:

Société Biom’up (CHU Montpellier), Dr Danièle Noël (IRMB, U1183, Montpellier)

Funding:

Industrial grant CIFRE Biom’up, MENRT grant (ED CBS2)

Evaluation of a biodegradable PLA–PEG–PLA internal biliary stent for liver transplantation: in vitro degradation and mechanical properties

J. Biomed. Mater. Res. 1-10, (2020)

Girard E., Chagnon G., Moreau-Gaudry A., Letoublon C., Favier D., Dejean S., Trilling B., Nottelet B.

 

ABSTRACT

Internal biliary stenting during biliary reconstruction in liver transplantation decrease anastomotic biliary complications. Implantation of a resorbable internal biliary stent (RIBS) is interesting since it would avoid an ablation gesture. The objective of present work was to evaluate adequacy of selected PLA-b-PEG-b-PLA copolymers for RIBS aimed to secure biliary anastomose during healing and prevent complications, such as bile leak and stricture. The kinetics of degradation and mechanical properties of a RIBS prototype were evaluated with respect to the main bile duct stenting requirements in liver transplantation. For this purpose, RIBS degradation under biliary mimicking solution versus standard phosphate buffer control solution was discussed. Morphological changes, mass loss, water uptake, molecular weight, permeability, pH variations, and mechanical properties were examined over time. The permeability and mechanical properties were evaluated under simulated biliary conditions to explore the usefulness of a PLA-b-PEG-b-PLA RIBS to secure biliary anastomosis. Results showed no pH influence on the kinetics of degradation, with degradable RIBS remaining impermeable for at least 8 weeks, and keeping its mechanical properties for 10 weeks. Complete degradation is reached at 6 months. PLA-b-PEG-b-PLA RIBS have the required in vitro degradation characteristics to secure biliary anastomosis in liver transplantation and envision in vivo applications

Biomimicking Fiber Platform with Tunable Stiffness to Study Mechanotransduction Reveals Stiffness Enhances Oligodendrocyte Differentiation but Impedes Myelination through YAP‐Dependent Regulation

Small 2020, 2003656

William Ong, Nicolas Marinval, Junquan Lin, Mui Hoon Nai, Yee-Song Chong, Coline Pinese, Sreedharan Sajikumar, Chwee Teck Lim, Charles Ffrench-Constant, Marie E. Bechler, and Sing Yian Chew

ABSTRACT

A key hallmark of many diseases, especially those in the central nervous system (CNS), is the change in tissue stiffness due to inflammation and scarring. However, how such changes in microenvironment affect the regenerative process remains poorly understood. Here, a biomimicking fiber platform that provides independent variation of fiber structural and intrinsic stiffness is reported. To demonstrate the functionality of these constructs as a mechanotransduction study platform, these substrates are utilized as artificial axons and the effects of axon structural versus intrinsic stiffness on CNS myelination are independently analyzed. While studies have shown that substrate stiffness affects oligodendrocyte differentiation, the effects of mechanical stiffness on the final functional state of oligodendrocyte (i.e., myelination) has not been shown prior to this. Here, it is demonstrated that a stiff mechanical microenvironment impedes oligodendrocyte myelination, independently and distinctively from oligodendrocyte differentiation. Yes-associated protein is identified to be involved in influencing oligodendrocyte myelination through mechanotransduction. The opposing effects on oligodendrocyte differentiation and myelination provide important implications for current work screening for promyelinating drugs, since these efforts have focused mainly on promoting oligodendrocyte differentiation. Thus, the platform may have considerable utility as part of a drug discovery program in identifying molecules that promote both differentiation and myelination.

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In Vivo Tissue-Engineered Vascular Grafts

Tissue-Engineered Vascular Grafts, Reference Series in
Biomedical Engineering

Walpoth B.H., de Valence S., Tille J-C., Mugnai D., Sologashvili T., Mrówczyński W.,
Cikirikcioglu M., Pektok E., Osorio S., Innocente F., Bochaton-Piallat M-L., Nottelet B., Kalangos A., Gurny R.

ABSTRACT

Vascular grafts are needed for coronary and peripheral vascular bypass surgeries as well as for access surgeries for hemodialysis and reconstruction of congenital heart defects. Despite good results in the large caliber, small caliber (<6 mm) show unsatisfactory clinical results. Tissue-engineered vascular grafts (TEVG) have been made using several approaches ranging from acellular synthetic or biologic polymer scaffolds to decellularized natural matrices, self-assembled cell-based bioreactor matured, or 3D cell-printed constructs. This chapter will focus mainly on in vivo tissue engineering which was used as first-in-man. This is based on an acellular, synthetic, degradable, polymer scaffold which is repopulated by the host cells after implantation to create a “neo-artery.” Advantages are shelf-readiness; simple, costeffective manufacturing; and avoidance of bioreactor cell maturation. Short-, mid-, and long-term experimental and clinical results show good cellular remodeling with extracellular matrix formation and endothelialization as well as patency and function. Thus, the approach of using an acellular, synthetic, biodegradable scaffold is an optimal clinical option for TEVG.

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From in vitro evaluation to human post-mortem pre-validation of a radiopaque and resorbable internal biliary stent for liver transplantation applications

Acta Biomaterialia 106, 66-81, (2020)

Girard E., Chagnon G., Broisat A., Dejean S., Soubies A., Gil H., Sharkawi T., Boucher F. Roth G.S., Trilling B., Nottelet B.

 

Girard E. et al. Acta Biomaterialia 2020

ABSTRACT

The implantation of an internal biliary stent (IBS) during liver transplantation has recently been shown to reduce biliary complications. To avoid a potentially morbid ablation procedure, we developed a resorbable and radiopaque internal biliary stent (RIBS). We studied the mechanical and radiological properties of RIBS upon in vivo implantation in rats and we evaluated RIBS implantability in human anatomical specimens.

For this purpose, a blend of PLA50-PEG-PLA50 triblock copolymer, used as a polymer matrix, and of X-ray-visible triiodobenzoate-poly(e-caprolactone) copolymer (PCL-TIB), as a radiopaque additive, was used to design X-ray-visible RIBS. Samples were implanted in the peritoneal cavity of rats. The radiological, chemical, and biomechanical properties were evaluated during degradation. Further histological studies were carried out to evaluate the degradation and compatibility of the RIBS. A human cadaver implantability study was also performed.

The in vivo results revealed a decline in the RIBS mechanical properties within 3 months, whereas clear and stable X-ray visualization of the RIBS was possible for up to 6 months. Histological analyses confirmed compatibility and resorption of the RIBS, with a limited inflammatory response. The RIBS could be successfully implanted in human anatomic specimens. The results reported in this study will allow the development of trackable and degradable IBS to reduce biliary complications after liver transplantation.

In vivo evaluation of hybrid patches composed of PLA based copolymers and collagen/chondroitin sulfate for ligament tissue regeneration: Hybrid Patches for Ligament Reconstruction

J. Biomed. Mater. Res. B 105, 1778–1788 (2017)

Pinese, C., Gagnieu, C., Nottelet, B., Rondot-Couzin, C., Hunger, S., Coudane, J. & Garric, X.

 

ABSTRACT

Biomaterials for soft tissues regeneration should exhibit sufficient mechanical strength, demonstrating a mechanical behavior similar to natural tissues and should also promote tissues ingrowth. This study was aimed at developing new hybrid patches for ligament tissue regeneration by synergistic incorporation of a knitted structure of degradable polymer fibers to provide mechanical strength and of a biomimetic matrix to help injured tissues regeneration. PLA‐ Pluronic® (PLA‐P) and PLA‐Tetronic® (PLA‐T) new copolymers were shaped as knitted patches and were associated with collagen I (Coll) and collagen I/chondroitine‐sulfate (Coll CS) 3‐dimensional matrices. In vitro study using ligamentocytes showed the beneficial effects of CS on ligamentocytes proliferation. Hybrid patches were then subcutaneously implanted in rats for 4 and 12 weeks. Despite degradation, patches retained strength to answer the mechanical physiological needs. Tissue integration capacity was assessed with histological studies. We showed that copolymers, associated with collagen and chondroitin sulfate sponge, exhibited very good tissue integration and allowed neotissue synthesis after 12 weeks in vivo. To conclude, PLA‐P/CollCS and PLA‐T/CollCS hybrid patches in terms of structure and composition give good hopes for tendon and ligament regeneration.

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Rolled knitted scaffolds based on PLA-pluronic copolymers for anterior cruciate ligament reinforcement: A step by step conception

J. Biomed. Mater. Res. B 105, 735–743 (2017)

Pinese, C., Gagnieu, C., Nottelet, B., Rondot-Couzin, C., Hunger, S., Coudane, J. & Garric, X.

 

ABSTRACT

The aim of this study was to prepare a new knitted scaffold from PLA‐Pluronic block copolymers for anterior cruciate ligament reconstruction. The impact of sterilization methods (beta‐ray and gamma‐ray sterilization) on copolymers was first evaluated in order to take into account the possible damages due to the sterilization process. Beta‐ray radiation did not significantly change mechanical properties in contrast to gamma‐ray sterilization. It was shown that ACL cells proliferate onto these copolymers, demonstrating their cytocompatibility. Thirdly, in order to study the influence of shaping on mechanical properties, several shapes were created with copolymers yarns: braids, ropes and linear or rolled knitted scaffolds. The rolled knitted scaffold presented interesting mechanical characteristics, similar to native anterior cruciate ligament (ACL) with a 67 MPa Young’s Modulus and a stress at failure of 22.5 MPa. These findings suggest that this three dimensional rolled knitted scaffold meet the mechanical properties of ligament tissues and could be suitable as a scaffold for ligament reconstruction.

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Jump to other drug delivery related subjects >>> Tissue engineering >>> Medical devices

Biomedical innovation

Hydrogels from biocompatible polymers for actinide decontamination

About the project:

Hydrogels from biocompatible polymers for actinide decontamination (DECAP). The DECAP project is focused on the development of innovative hydrogels prepared from polymeric materials for external actinide decontamination. The objective is to prepare new chelating macromolecules able to complex radionuclides with the controlled synthesis of complexing copolymers.

Contact:

Vincent Darcos
Vincent Darcos
Audrey Bethry
Audrey Bethry

Students:

Marie Le Roch
Marie Le Roch

Collaborations:

Florence Agnely (Institut Galien Paris-Sud), Nicolas Dacheux (Institut de Chimie Séparative de Marcoule), Sophie Monge (Institut Charles Gerhardt de Montpellier)

Funding:

ANR ASTRID

Long-term in vivo performances of polylactide / iron oxide nanoparticles core-shell fibrous nanocomposites as MRI-visible magneto-scaffolds

Biomat. Sci. XX, XXX–XXX (2021)

 Awada H., Seene S., Laurencin D., Lemaire L., Franconi F., Bernex F., Bethry A., Garric X., Guari Y., Nottelet B.

ABSTRACT

There is a growing interest in magnetic nanocomposites in biomaterials science. In particular, nanocomposites that combine poly(lactide) (PLA) nanofibers and super paramagnetic iron oxide nanoparticles (SPIONs), which can be obtained by either electrospinning of a SPIONs suspension in PLA or by precipitating SPIONs at the surface of PLA, are well documented in the literature. However, these two classical processes yield nanocomposites with altered materials properties, and their long-term in vivo fate and performances have in most cases only been evaluated over short periods of time. Recently, we reported a new strategy to prepare well-defined PLA@SPIONs nanofibers with a quasi-monolayer of SPIONs anchored at the surface of PLA electrospun fibers. Herein, we report on a 6-month in vivo rat implantation study with the aim of evaluating the long-term magnetic resonance imaging (MRI) properties of this new class of magnetic nanocomposites, as well as their tissue integration and degradation. Using clinically relevant T2-weighted MRI conditions, we show that the PLA@SPIONs nanocomposites are clearly visible up to 6 months. We also evaluate here by histological analyses the slow degradation of the PLA@SPIONs, as well as their biocompatibility. Overall, these results make these nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

Assessing the combination of magnetic field stimulation, iron oxide nanoparticles, and aligned electrospun fibers for promoting neurite outgrowth from dorsal root ganglia in vitro

Acta Biomaterialia 131, 302–313 (2021)

Funnell J.L., Ziemba A.M., Nowak J.F., Awada H., Prokopiou N., Samuel J., Guari Y., Nottelet B., Gilbert R.J.

ABSTRACT

Magnetic fiber composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and electrospun fibers have shown promise in tissue engineering fields. Controlled grafting of SPIONs to the fibers post-electrospinning generates biocompatible magnetic composites without altering desired fiber morphology. Here, for the first time, we assess the potential of SPION-grafted scaffolds combined with magnetic fields to promote neurite outgrowth by providing contact guidance from the aligned fibers and mechanical stimulation from the SPIONs in the magnetic field. Neurite outgrowth from primary rat dorsal root ganglia (DRG) was assessed from explants cultured on aligned control and SPION-grafted electrospun fibers as well as on non-grafted fibers with SPIONs dispersed in the culture media. To determine the optimal magnetic field stimulation to promote neurite outgrowth, we generated a static, alternating, and linearly moving magnet and simulated the magnetic flux density at different areas of the scaffold over time. The alternating magnetic field increased neurite length by 40% on control fibers compared to a static magnetic field. Additionally, stimulation with an alternating magnetic field resulted in a 30% increase in neurite length and 62% increase in neurite area on SPION-grafted fibers compared to DRG cultured on PLLA fibers with untethered SPIONs added to the culture media. These findings demonstrate that SPION-grafted fiber composites in combination with magnetic fields are more beneficial for stimulating neurite outgrowth on electrospun fibers than dispersed SPIONs.

Offre de CDD 1 an Ingénieur de Recherche – prestation industrielle

Poste d’ingénieur de recherche CDD 1 an: Caractérisation et déformulation d’un système de libération prolongée injectable

Le Département des Polymères pour la Santé est les Biomatériaux de l’IBMM souhaite recruter un Ingénieur de Recherche (<3 ans d’expérience) dans le cadre de la réalisation d’un contrat de prestation industrielle visant à caractériser et déformuler un système de libération prolongée injectable.

 

Contexte : Le Département des Polymères pour la Santé est les Biomatériaux de l’IBMM (https://ibmmpolymerbiomaterials.com/) souhaite recruter un Ingénieur de Recherche (<3 ans d’expérience) dans le cadre de la réalisation d’un contrat de prestation industrielle.

 

Mission principale : L’Ingénieur(e) de Recherche à recruter sera en charge d’une étude de déformulation d’un système de libération prolongée injectable fourni par l’entreprise mandante.

 

Activités : L’ingénieur(e) de Recherche sera amené à effectuer des analyses sur des formulations fournies par l’entreprise afin d’en identifier les composants. Suite à cette étape de déformulation, il(elle) devra synthétiser les composés identifiés et les utiliser pour préparer une formulation semblable à la formulation de référence. Cette formulation cible sera validée par l’entreprise mandante.

 

Compétences / qualifications : L’ingénieur de Recherche à recruter devra avoir de fortes compétences en analyse et caractérisation de formulations, en particulier contenant des polymères. Une expérience en synthèse macromoléculaire sera également la bienvenue. Les techniques d’analyse/caractérisation à maîtriser sont : chromatographie HPLC, chromatographie d’exclusion stérique (SEC), chromatographie préparative, spectroscopie de masse (en particulier Maldi-Tof), résonance magnétique nucléaire (RMN), calorimétrie différentielle (DSC), thermogravimétrie (TGA).

 

Date: début de contrat souhaité 1er septembre 2021

 

Responsable du projet : Prof. Benjamin Nottelet (benjamin.nottelet@umontpellier.fr)

 

Comment postuler : le(la) candidat(e) intéressé(e) doit faire parvenir au responsable du projet un CV détaillé, une lettre de motivation et le contact de 2 personnes référentes. Tout dossier non complet ne sera pas étudié.

 

Date limite de candidature : 30 juillet 2021.

 

 

Best practices in Regenerative Medicine

Save the date: next 23 June 2021  (from 10:00 to 11:15 am)

A seminar will be held on the Best practices in Regenerative Medicine

Link: https://unav.zoom.us/j/95703457456?pwd=VjNac1pUeklIM3owYmltK0lsNExqZz09
Meeting ID: 957 0345 7456
Passcode: 442924

best practice in regenerative medecine 2021

Implantable medical device for the capture and destruction of cancer cells in vivo.

About the project:

Contact:

Xavier Garric
Xavier Garric
Coline Pinese
Coline Pinese
Sylvie Hunger
Sylvie Hunger

Students:

MOULIN Marie
MOULIN Marie

Collaborations:

Dr Jean-Marie Ramirez (IBMM, Montpellier) ; Dr Benoit Charlot (IES, Montpellier)

Funding:

Region Occitanie, SATT AxLR CAPDCM

Long-term in vivo performances of polylactide / iron oxide nanoparticles core-shell fibrous nanocomposites as MRI-visible magneto-scaffolds

Biomat. Sci. XX, XXX–XXX (2021)

 Awada H., Seene S., Laurencin D., Lemaire L., Franconi F., Bernex F., Bethry A., Garric X., Guari Y., Nottelet B.

ABSTRACT

There is a growing interest in magnetic nanocomposites in biomaterials science. In particular, nanocomposites that combine poly(lactide) (PLA) nanofibers and super paramagnetic iron oxide nanoparticles (SPIONs), which can be obtained by either electrospinning of a SPIONs suspension in PLA or by precipitating SPIONs at the surface of PLA, are well documented in the literature. However, these two classical processes yield nanocomposites with altered materials properties, and their long-term in vivo fate and performances have in most cases only been evaluated over short periods of time. Recently, we reported a new strategy to prepare well-defined PLA@SPIONs nanofibers with a quasi-monolayer of SPIONs anchored at the surface of PLA electrospun fibers. Herein, we report on a 6-month in vivo rat implantation study with the aim of evaluating the long-term magnetic resonance imaging (MRI) properties of this new class of magnetic nanocomposites, as well as their tissue integration and degradation. Using clinically relevant T2-weighted MRI conditions, we show that the PLA@SPIONs nanocomposites are clearly visible up to 6 months. We also evaluate here by histological analyses the slow degradation of the PLA@SPIONs, as well as their biocompatibility. Overall, these results make these nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

Assessing the combination of magnetic field stimulation, iron oxide nanoparticles, and aligned electrospun fibers for promoting neurite outgrowth from dorsal root ganglia in vitro

Acta Biomaterialia 131, 302–313 (2021)

Funnell J.L., Ziemba A.M., Nowak J.F., Awada H., Prokopiou N., Samuel J., Guari Y., Nottelet B., Gilbert R.J.

ABSTRACT

Magnetic fiber composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and electrospun fibers have shown promise in tissue engineering fields. Controlled grafting of SPIONs to the fibers post-electrospinning generates biocompatible magnetic composites without altering desired fiber morphology. Here, for the first time, we assess the potential of SPION-grafted scaffolds combined with magnetic fields to promote neurite outgrowth by providing contact guidance from the aligned fibers and mechanical stimulation from the SPIONs in the magnetic field. Neurite outgrowth from primary rat dorsal root ganglia (DRG) was assessed from explants cultured on aligned control and SPION-grafted electrospun fibers as well as on non-grafted fibers with SPIONs dispersed in the culture media. To determine the optimal magnetic field stimulation to promote neurite outgrowth, we generated a static, alternating, and linearly moving magnet and simulated the magnetic flux density at different areas of the scaffold over time. The alternating magnetic field increased neurite length by 40% on control fibers compared to a static magnetic field. Additionally, stimulation with an alternating magnetic field resulted in a 30% increase in neurite length and 62% increase in neurite area on SPION-grafted fibers compared to DRG cultured on PLLA fibers with untethered SPIONs added to the culture media. These findings demonstrate that SPION-grafted fiber composites in combination with magnetic fields are more beneficial for stimulating neurite outgrowth on electrospun fibers than dispersed SPIONs.

Offre de CDD 1 an Ingénieur de Recherche – prestation industrielle

Poste d’ingénieur de recherche CDD 1 an: Caractérisation et déformulation d’un système de libération prolongée injectable

Le Département des Polymères pour la Santé est les Biomatériaux de l’IBMM souhaite recruter un Ingénieur de Recherche (<3 ans d’expérience) dans le cadre de la réalisation d’un contrat de prestation industrielle visant à caractériser et déformuler un système de libération prolongée injectable.

 

Contexte : Le Département des Polymères pour la Santé est les Biomatériaux de l’IBMM (https://ibmmpolymerbiomaterials.com/) souhaite recruter un Ingénieur de Recherche (<3 ans d’expérience) dans le cadre de la réalisation d’un contrat de prestation industrielle.

 

Mission principale : L’Ingénieur(e) de Recherche à recruter sera en charge d’une étude de déformulation d’un système de libération prolongée injectable fourni par l’entreprise mandante.

 

Activités : L’ingénieur(e) de Recherche sera amené à effectuer des analyses sur des formulations fournies par l’entreprise afin d’en identifier les composants. Suite à cette étape de déformulation, il(elle) devra synthétiser les composés identifiés et les utiliser pour préparer une formulation semblable à la formulation de référence. Cette formulation cible sera validée par l’entreprise mandante.

 

Compétences / qualifications : L’ingénieur de Recherche à recruter devra avoir de fortes compétences en analyse et caractérisation de formulations, en particulier contenant des polymères. Une expérience en synthèse macromoléculaire sera également la bienvenue. Les techniques d’analyse/caractérisation à maîtriser sont : chromatographie HPLC, chromatographie d’exclusion stérique (SEC), chromatographie préparative, spectroscopie de masse (en particulier Maldi-Tof), résonance magnétique nucléaire (RMN), calorimétrie différentielle (DSC), thermogravimétrie (TGA).

 

Date: début de contrat souhaité 1er septembre 2021

 

Responsable du projet : Prof. Benjamin Nottelet (benjamin.nottelet@umontpellier.fr)

 

Comment postuler : le(la) candidat(e) intéressé(e) doit faire parvenir au responsable du projet un CV détaillé, une lettre de motivation et le contact de 2 personnes référentes. Tout dossier non complet ne sera pas étudié.

 

Date limite de candidature : 30 juillet 2021.

 

 

Best practices in Regenerative Medicine

Save the date: next 23 June 2021  (from 10:00 to 11:15 am)

A seminar will be held on the Best practices in Regenerative Medicine

Link: https://unav.zoom.us/j/95703457456?pwd=VjNac1pUeklIM3owYmltK0lsNExqZz09
Meeting ID: 957 0345 7456
Passcode: 442924

best practice in regenerative medecine 2021

3D printing and shaping processes for improved medical devices

About the project:

Contact:

Coline Pinese
Coline Pinese
Stéphane Dejean
Stéphane Dejean
Xavier Garric
Xavier Garric
Benjamin Nottelet
Benjamin Nottelet

Students:

Mathilde Grosjean
Mathilde Grosjean
Mathilde Massonié
Mathilde Massonié

Collaborations:

 

Funding:

PLA scaffolds production from Thermally Induced Phase Separation: Effect of process parameters and development of an environmentally improved route assisted by supercritical carbon dioxide

Supercrit. Fluids 136, 123–135 (2018)

Gay, S., Lefebvre, G., Bonnin, M., Nottelet, B., Boury, F., Gibaud, A. & Calvignac, B.

ABSTRACT

In this work, a relatively large scale of PLA scaffolds was produced using thermally induced phase separation (TIPS) combined with a supercritical carbon dioxide (SC-CO2) drying step as a green alternative. For the TIPS step, the phase separation of PLA and 1,4-dioxane solvent was controlled by adjusting the process conditions such as the polymer concentration and molecular weight, the 1,4-dioxane solvent power and the cooling conditions. The scaffolds morphology was analyzed by scanning electron microscopy. Their structural and mechanical properties were correlated together with the possibility to tune them by controlling the process conditions. An environmental analysis using the Life Cycle Assessment (LCA) methodology confirmed a reduction of at least 50% of the environmental impact of the whole process using the SC-CO2 drying compared to the traditional freeze-drying technology. This work is the first known attempt to conduct the LCA methodology on TIPS process for the PLA scaffolds production.

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