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Micro & Nano Biomedical innovation Biomaterials for tissue engineering Tissue engineering & medical devices Medical devices

Tissue engineering and medical devices

Jump to other drug delivery related subjects >>> Medical devices >>> Biomedical innovation

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:

Louis Gangolphe
Louis Gangolphe

Collaborations:

Pr. Frederic Bossard (LRP, Université de Grenoble Alpes), Pr. Denis Favier, Dr. Grégory Chagnon, Dr. Arnaud Chauvière (TIMC-IMAG, Université de Grenoble Alpes)

Funding:

ANR Bioscaff

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

Modulation of protein release from penta-block copolymer microspheres European Journal of Pharmaceutics and Biopharmaceutics 152, 175–182 (2020)

European Journal of Pharmaceutics and Biopharmaceutics 152, 175–182 (2020).

Minh-Quan Le, Jean-Christophe Gimel, Xavier Garric, Thao-Quyen Nguyen-Pham, Cédric Paniagua, Jérémie Riou, Marie-Claire Venier-Julienne,

 

ABSTRACT

Releasing a protein according to a zero-order profile without protein denaturation during the polymeric microparticle degradation process is very challenging. The aim of the current study was to develop protein-loaded microspheres with new PLGA based penta-block copolymers for a linear sustained protein release. Lysozyme was chosen as model protein and 40 µm microspheres were prepared using the solid-in-oil-in-water solvent extraction/evaporation process. Two types of PLGA-P188-PLGA penta-block copolymers were synthetized with two PLGA-segments molecular weight (20 kDa or 40 kDa). The resulting microspheres (50P20-MS and 50P40-MS) had the same size, an encapsulation efficiency around 50–60% but different porosities. Their protein release profiles were complementary: linear but non complete for 50P40-MS, non linear but complete for 50P20-MS. Two strategies, polymer blending and microsphere mixing, were considered to match the release to the desired profile. The (1:1) microsphere mixture was successful. It induced a bi-phasic release with a moderate initial burst (around 13%) followed by a nearly complete linear release for 8 weeks. This study highlighted the potential of this penta-block polymer where the PEO block mass ratio influence clearly the Tg and consequently the microsphere structure and the release behavior at 37 °C. The (1:1) mixture was a starting point but could be finely tuned to control the protein release.

In Vivo Evaluation of the Efficacy and Safety of a Novel Degradable Polymeric Film for the Prevention of Intrauterine Adhesions.

Journal of Minimally Invasive Gynecology (2020)

Stéphanie Huberlant, Salomé Leprince, Lucie Allegre, Sophie Warembourg, Isabelle Leteuff, Hubert Taillades, Xavier Garric., Renaud de Tayrac, Vincent Letouzey.

ABSTRACT

To study the safety of a degradable polymeric film (DPF) and its efficacy on reducing the risk of intrauterine-adhesion (IUA) formation in a rat model.A series of case-control studies relying on random allocation, where feasible.The animal models comprised female and male Oncins France Strain A and female Wistar rats.The Oncins France Strain A rats were used for in vivo evaluation of the impact of the DPF on endometrial thickness and its effect on fertility. For in vivo evaluation of the biologic response, 40 Wistar rats were randomly allocated to intervention and control groups, with matched sampling time after surgery. Finally, for the in vivo evaluation of the DPF’s efficacy on IUA prevention, a total of 24 Wistar rats were divided into 3 groups: 1 treated with the DPF, 1 treated with hyaluronic acid gel, and a sham group. The DPF did not have a significant impact on endometrial thickness, and there were no significant differences in the number of conceived or prematurely terminated pregnancies, confirming its noninferiority to no treatment. The DPF did not induce irritation at 5 days and 28 days. Finally, the DPF significantly reduced the likelihood of complete IUA formation compared with hyaluronic acid gel– and sham-implanted animals, where only 27% of the animals had their uterine cavity obliterated compared with 80% and 100%, respectively.The DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

Hyaluronic Acid-Poly(N-acryloyl glycinamide) Copolymers as Sources of Degradable Thermoresponsive Hydrogels for Therapy

Gels 2020, 6(4), 42

Mahfoud Boustta and Michel Vert

 

ABSTRACT

One-pot free-radical polymerization of N-acryloyl glycinamide in the presence of hyaluronic acid as transfer-termination agent led to new copolymers in high yields without any chemical activation of hyaluronic acid before. All the copolymers formed thermoresponsive hydrogels of the Upper Critical Solution Temperature-type in aqueous media. Gel properties and the temperature of the reversible gel ↔ sol transition depended on feed composition and copolymer concentration. Comparison with mixtures of hyaluronic acid-poly(N-acryloyl glycinamide) failed in showing the expected formation of graft copolymers conclusively because poly(N-acryloyl glycinamide) homopolymers are also thermoresponsive. Grafting and formation of comb-like copolymers were proved after degradation of inter-graft hyaluronic acid segments by hyaluronidase. Enzymatic degradation yielded poly(N-acryloyl glycinamide) with sugar residues end groups as shown by NMR. In agreement with the radical transfer mechanism, the molar mass of these released poly(N-acryloyl glycinamide) grafts depended on the feed composition. The higher the proportion of hyaluronic acid in the feed, the lower the molar mass of poly(N-acryloyl glycinamide) grafts was. Whether molar mass can be made low enough to allow kidney filtration remains to be proved in vivo. Last but not least, Prednisolone was used as model drug to show the ability of the new enzymatically degradable hydrogels to sustain progressive delivery for rather long periods of time in vitro.DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

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)

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:

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

Funding:

CNRS interdisciplinary PhD program

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

Modulation of protein release from penta-block copolymer microspheres European Journal of Pharmaceutics and Biopharmaceutics 152, 175–182 (2020)

European Journal of Pharmaceutics and Biopharmaceutics 152, 175–182 (2020).

Minh-Quan Le, Jean-Christophe Gimel, Xavier Garric, Thao-Quyen Nguyen-Pham, Cédric Paniagua, Jérémie Riou, Marie-Claire Venier-Julienne,

 

ABSTRACT

Releasing a protein according to a zero-order profile without protein denaturation during the polymeric microparticle degradation process is very challenging. The aim of the current study was to develop protein-loaded microspheres with new PLGA based penta-block copolymers for a linear sustained protein release. Lysozyme was chosen as model protein and 40 µm microspheres were prepared using the solid-in-oil-in-water solvent extraction/evaporation process. Two types of PLGA-P188-PLGA penta-block copolymers were synthetized with two PLGA-segments molecular weight (20 kDa or 40 kDa). The resulting microspheres (50P20-MS and 50P40-MS) had the same size, an encapsulation efficiency around 50–60% but different porosities. Their protein release profiles were complementary: linear but non complete for 50P40-MS, non linear but complete for 50P20-MS. Two strategies, polymer blending and microsphere mixing, were considered to match the release to the desired profile. The (1:1) microsphere mixture was successful. It induced a bi-phasic release with a moderate initial burst (around 13%) followed by a nearly complete linear release for 8 weeks. This study highlighted the potential of this penta-block polymer where the PEO block mass ratio influence clearly the Tg and consequently the microsphere structure and the release behavior at 37 °C. The (1:1) mixture was a starting point but could be finely tuned to control the protein release.

In Vivo Evaluation of the Efficacy and Safety of a Novel Degradable Polymeric Film for the Prevention of Intrauterine Adhesions.

Journal of Minimally Invasive Gynecology (2020)

Stéphanie Huberlant, Salomé Leprince, Lucie Allegre, Sophie Warembourg, Isabelle Leteuff, Hubert Taillades, Xavier Garric., Renaud de Tayrac, Vincent Letouzey.

ABSTRACT

To study the safety of a degradable polymeric film (DPF) and its efficacy on reducing the risk of intrauterine-adhesion (IUA) formation in a rat model.A series of case-control studies relying on random allocation, where feasible.The animal models comprised female and male Oncins France Strain A and female Wistar rats.The Oncins France Strain A rats were used for in vivo evaluation of the impact of the DPF on endometrial thickness and its effect on fertility. For in vivo evaluation of the biologic response, 40 Wistar rats were randomly allocated to intervention and control groups, with matched sampling time after surgery. Finally, for the in vivo evaluation of the DPF’s efficacy on IUA prevention, a total of 24 Wistar rats were divided into 3 groups: 1 treated with the DPF, 1 treated with hyaluronic acid gel, and a sham group. The DPF did not have a significant impact on endometrial thickness, and there were no significant differences in the number of conceived or prematurely terminated pregnancies, confirming its noninferiority to no treatment. The DPF did not induce irritation at 5 days and 28 days. Finally, the DPF significantly reduced the likelihood of complete IUA formation compared with hyaluronic acid gel– and sham-implanted animals, where only 27% of the animals had their uterine cavity obliterated compared with 80% and 100%, respectively.The DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

Hyaluronic Acid-Poly(N-acryloyl glycinamide) Copolymers as Sources of Degradable Thermoresponsive Hydrogels for Therapy

Gels 2020, 6(4), 42

Mahfoud Boustta and Michel Vert

 

ABSTRACT

One-pot free-radical polymerization of N-acryloyl glycinamide in the presence of hyaluronic acid as transfer-termination agent led to new copolymers in high yields without any chemical activation of hyaluronic acid before. All the copolymers formed thermoresponsive hydrogels of the Upper Critical Solution Temperature-type in aqueous media. Gel properties and the temperature of the reversible gel ↔ sol transition depended on feed composition and copolymer concentration. Comparison with mixtures of hyaluronic acid-poly(N-acryloyl glycinamide) failed in showing the expected formation of graft copolymers conclusively because poly(N-acryloyl glycinamide) homopolymers are also thermoresponsive. Grafting and formation of comb-like copolymers were proved after degradation of inter-graft hyaluronic acid segments by hyaluronidase. Enzymatic degradation yielded poly(N-acryloyl glycinamide) with sugar residues end groups as shown by NMR. In agreement with the radical transfer mechanism, the molar mass of these released poly(N-acryloyl glycinamide) grafts depended on the feed composition. The higher the proportion of hyaluronic acid in the feed, the lower the molar mass of poly(N-acryloyl glycinamide) grafts was. Whether molar mass can be made low enough to allow kidney filtration remains to be proved in vivo. Last but not least, Prednisolone was used as model drug to show the ability of the new enzymatically degradable hydrogels to sustain progressive delivery for rather long periods of time in vitro.DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

OFFRE DE POSTE D’INGENIEUR D’ETUDE CONCEPTION DE NANOFIBRES CHARGEES EN FACTEUR DE CROISSANCE POUR LA REGENERATION DU MUSCLE CARDIAQUE

-Poste pourvu-

OFFRE DE POSTE D’INGÉNIEUR D’ÉTUDE CONCEPTION DE NANOFIBRES CHARGÉES EN FACTEUR DE CROISSANCE POUR LA RÉGÉNÉRATION DU MUSCLE CARDIAQUE

Contexte :

Le travail aura lieu :

Institut des Biomolécules Max Mousseron, UMR CNRS 5247, Equipe biopolymères artificiels

Faculté de Pharmacie, Université Montpellier

https://ibmmpolymerbiomaterials.com/

Notre équipe est spécialisée dans la synthèse de polymères pour la santé et s’intéresse en particulier aux polymères pour la régénération des tissus mous. L’ingénieur d’étude travaillera sur le projet pluridisciplinaire INTERREG-SUDOE CARDIOPATCH, qui implique de nombreuses équipes françaises, espagnoles et portugaises aux savoir-faire très différents et complémentaires. L’objectif du projet CARDIOPATCH est le développement de patchs cardiaques favorisant la re-cellularisation du myocarde après infarctus du myocarde.

Durée du contrat 15 mois- Début : début janvier 2021

Mission principale :

 

L’ingénieur(e) à recruter sera en charge du développement de nouveaux patch fonctionnels associant un patch commercial à base de polymère naturel qui sera optimisé par le biais de nanofibres polymères fonctionnalisés incorporant des facteurs de croissance. L’objectif final est de booster la régénération cardiaque sur 3 semaines.

 Activités :

 

Afin de répondre à cette problématique nous envisageons :

  • 1/ la fabrication de nanofibres bioactives,
  • 2/ l’association des nanofibres aux patchs (adhésion électrostatique mais aussi greffages chimiques)
  • 3/ la vérification de la cinétique de libération des facteurs de croissance
  • 4/ la vérification de la cytocompatibilité

 

 Compétences / qualifications :

 

Le(la) candidat(e) retenue devra être motivé(e) par le domaine de l’ingénierie tissulaire, capable de mener des recherches rapides et de travailler de manière autonome dans un environnement axé sur le travail en équipe au sein d’un réseau international. De plus, la personne recrutée devra faire preuve d’esprit d’innovation, d’organisation et d’autonomie et elle devra posséder un très bon relationnel et être communicante. La/le candidat(e) devra avoir de l’expérience à l’interface chimie/biologie.

Liste des compétences souhaitées :

  • Electrospinning
  • Cinétique de libération d’actifs
  • Connaissances en chimie des matériaux et plus particulièrement de polymères dégradables (Synthèse, caractérisation, propriétés mécaniques)
  • Culture cellulaire
  • Motivation pour la résolution de problèmes scientifiques
  • Capacité à lire et communiquer en anglais.
  • Très bonne qualité rédactionnelle et de synthèse.

 

Envoyer un CV, une lettre de motivation ainsi que les contacts d’au moins deux personnes référentes.

  • Contacts :
  • Dr Coline PINESE & Pr Benjamin NOTTELET
  • +33(0)4 11 75 97 10 et +33(0)4 11 75 96 97

Coline.pinese@umontpellier.fr et Benjamin.Nottelet@umontpellier.fr

Offre de stage « Hydrogels pour la décontamination corporelle d’actinides à base de polymères biocompatibles »

Projet :

Ce projet 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).

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

Laboratoire d’accueil :

Le stage se déroulera au sein de l’Institut des Biomolécules Max Mousseron (IBMM) à Montpellier. Contact : Dr Vincent Darcos

Durée du stage : 6 mois maximum

Profil du candidat recherché :

Etudiant(e) en formation Master et/ou Ingénieur dans les domaines de la chimie organique ou de la chimie des polymères. Des connaissances et des compétences en synthèse organique et/ou des polymères seront nécessaires. Goût pour aborder un sujet de recherche expérimental et pluridisciplinaire.

 

Modalités de candidature :

Merci d’envoyer votre CV et votre lettre de motivation par courrier électronique à Vincent DARCOS Email: vincent.darcos@umontpellier.fr.

Offre de stage M2: Hydrogels hybrides polyester-polysaccharide photo-clivables pour photo-impression 3D (3DP-BioGel)

Laboratoire d’accueil : Département des « Polymères pour la Santé et les Biomatériaux », Institut des Biomolécules Max Mousseron (IBMM) (https://ibmmpolymerbiomaterials.com/) / Faculté de Pharmacie de Montpellier.

 

Mots-clés : Modifications chimiques de polymères, synthèses de copolymères, formulation-caractérisations d’hydrogels, photo-réticulation, biomatériaux, impression 3D photo-guidée, dégradation photo-déclenchée, délivrance de principes actifs.

 

Les hydrogels occupent une place prépondérante dans de nombreuses stratégies thérapeutiques innovantes (gestion des plaies chroniques, dépôt sous-cutanés de réservoir d’anticancéreux, ingénierie tissulaire etc…). Le projet 3DP-BioGel vise la préparation d’hydrogels hybrides polyester-polysaccharide compatibles avec la technique d’impression 3D photo-activée pour concevoir des pansements bioactifs avec libération contrôlée d’anti-inflammatoires. Lors de ce stage, une partie chimie consistera à préparer les dérivés de polyester et polysaccharide par modifications chimiques. Des hydrogels seront ensuite préparés par réticulation UV et leurs propriétés mécaniques seront étudiées par rhéologie. Une phase d’optimisation consistera à étudier plusieurs paramètres (fonctions réactives, degré de substitution, masses molaires…) afin de moduler les propriétés mécaniques et contrôler la dégradation des hydrogels. La biocompatibilité des hydrogels sera évaluée suivant les normes en vigueur pour s’assurer d’un développement réaliste de ces biomatériaux. En fonction de l’avancée du projet, la libération in vitro d’anti-inflammatoires, préalablement encapsulés dans les hydrogels, pourra également être étudiée.

 

 

Profil candidat : nous recherchons un(e) étudiant(e) chimiste, curieux(se) et motivé(e), avec des compétences en synthèse organique et en caractérisations physico-chimiques (RMN, FT-IR…). Une expérience en chimie des polymères est un plus.

 

Encadrants à contacter pour candidater :

Hélène Van Den Berghe : helene.van-den-berghe@umontpellier.fr     04-11-75-97-09

Benjamin Nottelet: benjamin.nottelet@umontpellier.fr     04-11-75-96-97

A new exciting adventure begins

A new exciting adventure begins :
Regenerative Medicine and 3D Printing Technology in the Treatment of Myocardial Infarction
  •  The CARDIOPATCH project, funded by the EU Interreg Sudoe Programme, aims to develop a smart biotechnology solution capable of regenerating damaged tissue after infarction.
  • A secondary aim of the project is to create an excellence network to foster R&D and innovation applied to the biomedical sector in South West Europe.
  • The project is headed by a consortium of nine institutions from Spain, France and Portugal.

Cardiovascular disease (CVD) is the number one cause of death globally. This group of disorders accounts from 45% of deaths in Europe and, according to figures from the European Heart Network, is estimated to cost the EU economy €210 billion each year.

It is in this context that the CARDIOPATCH project is being developed. Co-funded by the EU Interreg Sudoe Programme, via the European Regional Development Fund (ERDF), it is investigating new treatments for myocardial infarction and aims to provide solutions to improve patients’ quality of life.

Headed by Navarra University Clinic (CUN), the project involves nine centres from Spain, France and Portugal with expertise in cardiology, cell therapy, nanotechnology, 3D printing, bioengineering and technology transfer.

CARDIOPATCH, which had its kick-off meeting on the 15th and 16th of December and is expected to run into April 2023, will concentrate on developing a “smart” patch able to regenerate tissues damaged by infarction.

With this aim, the project partners will work on a collagen fibre patch impregnated with mesenchymal stem cells taken from body fat. The patch is currently in the first phase of a clinical trial on patients with chronic ischaemic cardiomyopathy.

The CARDIOPATCH team aims to optimise the therapeutic benefit of the patch using genetic modification and cell reprogramming techniques.

“To design the new solution, we will genetically modify mesenchymal stem cells from adipose tissue using microRNA and viral vectors that induce expression of proangiogenic and cardioprotective proteins. This will stimulate the formation of new blood vessels in damaged areas of the heart and facilitate their repair,” explains Felipe Prósper, director of the Navarra University Clinic Cell Therapy Department and project chief scientific officer.

The regenerative capacity of the patch’s collagen membrane will also be enhanced by adding cardiomyocytes, which are the cells that make up the cardiac muscle. “These cells will be generated using cell reprogramming techniques derived from induced pluripotent stem cells, i.e. artificially created stem cells,” he adds.

In addition to therapeutically validating the new patch, the project also aims to develop another two products: a roll-up 3D device which will allow the patch to be implanted by means of less invasive methods than currently available, and a 3D system to generalise production and streamline transport of the patch.

“The surgical technique currently available for implanting the patch into patients is via thoracotomy. However, we are hoping to develop a roll-up 3D device that will enable us to implant it via mini-thoracotomy. In this way, a new, roll-up design of the patch would allow us to introduce it via a small incision and guide it to the damaged area of the heart. Once there, it would be unrolled and attached to the lesion, activating regeneration,” says Prósper.

An Excellence Network to Foster Biomedical R&D and Innovation

In addition to developing advanced solutions, another of the aims of the CARDIOPATCH project is to create an “Excellence Network” to foster R&D and innovation in the biomedical sector in South West Europe, with the intention of extending industry 4.0 technologies into the healthcare sector.

The CARDIOPATCH Excellence Network will foster cooperation with public authorities in participating regions by rolling out tools and services to keep them informed of the latest developments in regenerative cardiac medicine, aiding the strategic decision-making process.

The project also aims to involve society. To do this, it will organise a series of outreach activities and training workshops on breakthroughs in research.

With a total budget of €1.419 million, the CARDIOPATCH consortium is made up of CUN, CIMA University of Navarra, via the Foundation for Applied Medical Research, the Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, LEARTIKER technology centre, communication agency GUK, Centre Hospitalier Universitaire de Toulouse, the University of Montpellier (UM) – Institut des Biomolécules Max Mousseron (IBMM), GenIbet Biopharmaceuticals and the Instituto de Biologia Experimental e Tecnológica.

The project also has the support of associate partners Viscofan, Sodena and the Nouvelle-Aquitaine, Euskadi, Navarre Euroregion (NAEN).

Partners in the CARDIOPATCH European consortium:

Spain:

–           Navarra University Clinic

–           CIMA Universidad de Navarra, via the Foundation for Applied Medical Research

–           Fundación Institut de Recerca de L’ Hospital de la Santa Creu i Sant Pau

–           LEARTIKER (Spain)

–           GUK Komunikazio Aholkularitza

France:

–           Centre Hospitalier Universitaire de Toulouse

–           Université de Montpellier (UM) – Institut des Biomolécules Max Mousseron (IBMM)

Portugal:

–           Instituto de Biologia Experimental e Tecnológica

–          GenIbet Biopharmaceuticals S.A.

Project Full Name: Network of Excellence for the development of Advanced Therapies of Myocardial Infarction Treatment based on Regenerative Medicine and 3D Printing.

Acronym: CARDIOPATCH

Offre de these 2021- Nanocomposites

OFFRE DE THESE

Développement de matériaux nanocomposites poreux pour le traitement de l’ostéoradionécrose mandibulaire

 

SUJET

Les cancers ORL sont au 5ème rang en France en termes d’incidence. On estime à 7500 nouveaux cas par an en France de cancer de la cavité orale. Plus de 70% des patients avec un cancer de la cavité buccale ou de l’oropharynx bénéficient d’un traitement par radiothérapie. L’ostéoradionécrose est une complication tardive et sévère de la radiothérapie et son incidence est estimée à 10%.

L’objectif de ce projet de thèse est le développement d’un matériau composite organique-inorganique poreux, pro-angiogénique et antibactérien pour la reconstruction osseuse consécutive à une ostéoradionécrose (taille de défauts osseux supérieures à 1 cm). La fonctionnalisation à façon de particules inorganiques de bioverre par des polymères dégradables de type poly(acide lactique) sera couplée au procédé « freeze-casting » (congélation dirigée pour la génération de porosité) pour permettre le contrôle fin des propriétés du nanocomposite final. L’effet de différents paramètres (type de particules, nature et fonctionnalisation des polymères, taux de greffage, solvant, gradient de température…) sur la porosité (organisation, taille) et sur les propriétés physico-chimiques et biologiques du substitut osseux sera étudié.

La méthodologie qui sera suivie au cours de cette thèse vise à établir un lien entre la composition et la structure multi-échelle de ces matériaux poreux d’une part, et leurs propriétés physico-chimiques et biologiques d’autre part. Elle inclut notamment les grandes étapes suivantes : 1) Synthèse et caractérisation des nanoparticules de bioverre et des (co)polymères, 2) Fonctionnalisation des nanoparticules minérales avec le polymère (particules core-shell), 3) Elaboration des scaffolds nanocomposites poreux par freeze-casting, 4) Etude de la porosité et des propriétés mécaniques du matériau, 5) Etude des mécanismes physico-chimiques de dégradation in vitro, 6) Evaluation des propriétés biologiques in vitro (cytocompatibilité et comportement antibactérien).

Cette thèse pluridisciplinaire s’inscrit dans le cadre du projet CongOs (2021-2025) financé par l’Agence Nationale de la Recherche (ANR). Il s’appuiera sur un consortium de cinq partenaires académiques et un partenaire industriel, aux domaines de compétences et d’expertises complémentaires (chimistes des polymères, chimistes des matériaux, physiciens, biologistes, chirurgien et ingénieurs R&D).

LABORATOIRES D’ACCUEIL 

La thèse se déroulera pour partie au sein de l’équipe Biopolymères Artificiels de l’IBMM à Montpellier (https://ibmmpolymerbiomaterials.com) et au sein de l’équipe Phosphates, Pharmacotechnie, Biomatériaux du CIRIMAT à Toulouse (https://www.cirimat.cnrs.fr/spip.php?rubrique24).

FINANCEMENT DE LA THESE : Contrat doctoral de 3 ans

Salaire net mensuel : 1710€ euros /Date de début de la thèse : 04 janvier 2021

 

PROFIL DU CANDIDAT RECHERCHE 

Etudiant·e en formation Master et/ou Ingénieur dans le domaine de la chimie des matériaux. Des connaissances et compétences en synthèse/élaboration par chimie douce, en synthèse des polymères et en caractérisation physico-chimique des matériaux sont nécessaires. Une expérience dans le domaine des biomatériaux serait un plus. Goût pour aborder un sujet de recherche expérimental et pluridisciplinaire.

MODALITES DE CANDIDATURE

Merci d’envoyer votre CV et votre lettre de motivation par courrier électronique à Vincent DARCOS et Jérémy SOULIÉ au plus tard le 2 novembre 2020 en indiquant “Candidature thèse” en objet de votre email.

Emails : vincent.darcos@umontpellier.fr et jeremy.soulie@toulouse-inp.fr

MODALITES DE SELECTION

Le recrutement sera réalisé en plusieurs étapes :

1) sur la base du CV et de la lettre de motivation, puis

2) via un entretien pour les candidat·e·s pré-selectionné·e·s sur dossier. Durant ces deux étapes, les critères de sélection incluront :

– Les compétences du candidat en fonction du profil recherché : compétences scientifiques pour traiter le sujet de recherche proposé et compétences transverses pour mener le projet de recherche à terme.

– La cohérence de la formation doctorale proposée dans le projet professionnel du candidat.

– Les capacités d’adaptation à un nouvel environnement et l’intégration future du candidat dans les laboratoires d’accueil.

– Le niveau d’anglais et de français.
3) Les candidatures seront à déposer en parallèle sur le portail du CNRS et celui de l’Ecole Doctorale Sciences Chimiques Balard et une demande d’accès à une zone à régime restrictif (ZRR) devra autoriser le recrutement.

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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:

Coline Pinese
Coline Pinese
Adrien Leroy

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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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:

Carlos Arrambide Cruz
Carlos Arrambide Cruz
Anita Schulz
Sarah El Habnouni

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

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

Modulation of protein release from penta-block copolymer microspheres European Journal of Pharmaceutics and Biopharmaceutics 152, 175–182 (2020)

European Journal of Pharmaceutics and Biopharmaceutics 152, 175–182 (2020).

Minh-Quan Le, Jean-Christophe Gimel, Xavier Garric, Thao-Quyen Nguyen-Pham, Cédric Paniagua, Jérémie Riou, Marie-Claire Venier-Julienne,

 

ABSTRACT

Releasing a protein according to a zero-order profile without protein denaturation during the polymeric microparticle degradation process is very challenging. The aim of the current study was to develop protein-loaded microspheres with new PLGA based penta-block copolymers for a linear sustained protein release. Lysozyme was chosen as model protein and 40 µm microspheres were prepared using the solid-in-oil-in-water solvent extraction/evaporation process. Two types of PLGA-P188-PLGA penta-block copolymers were synthetized with two PLGA-segments molecular weight (20 kDa or 40 kDa). The resulting microspheres (50P20-MS and 50P40-MS) had the same size, an encapsulation efficiency around 50–60% but different porosities. Their protein release profiles were complementary: linear but non complete for 50P40-MS, non linear but complete for 50P20-MS. Two strategies, polymer blending and microsphere mixing, were considered to match the release to the desired profile. The (1:1) microsphere mixture was successful. It induced a bi-phasic release with a moderate initial burst (around 13%) followed by a nearly complete linear release for 8 weeks. This study highlighted the potential of this penta-block polymer where the PEO block mass ratio influence clearly the Tg and consequently the microsphere structure and the release behavior at 37 °C. The (1:1) mixture was a starting point but could be finely tuned to control the protein release.

In Vivo Evaluation of the Efficacy and Safety of a Novel Degradable Polymeric Film for the Prevention of Intrauterine Adhesions.

Journal of Minimally Invasive Gynecology (2020)

Stéphanie Huberlant, Salomé Leprince, Lucie Allegre, Sophie Warembourg, Isabelle Leteuff, Hubert Taillades, Xavier Garric., Renaud de Tayrac, Vincent Letouzey.

ABSTRACT

To study the safety of a degradable polymeric film (DPF) and its efficacy on reducing the risk of intrauterine-adhesion (IUA) formation in a rat model.A series of case-control studies relying on random allocation, where feasible.The animal models comprised female and male Oncins France Strain A and female Wistar rats.The Oncins France Strain A rats were used for in vivo evaluation of the impact of the DPF on endometrial thickness and its effect on fertility. For in vivo evaluation of the biologic response, 40 Wistar rats were randomly allocated to intervention and control groups, with matched sampling time after surgery. Finally, for the in vivo evaluation of the DPF’s efficacy on IUA prevention, a total of 24 Wistar rats were divided into 3 groups: 1 treated with the DPF, 1 treated with hyaluronic acid gel, and a sham group. The DPF did not have a significant impact on endometrial thickness, and there were no significant differences in the number of conceived or prematurely terminated pregnancies, confirming its noninferiority to no treatment. The DPF did not induce irritation at 5 days and 28 days. Finally, the DPF significantly reduced the likelihood of complete IUA formation compared with hyaluronic acid gel– and sham-implanted animals, where only 27% of the animals had their uterine cavity obliterated compared with 80% and 100%, respectively.The DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

Hyaluronic Acid-Poly(N-acryloyl glycinamide) Copolymers as Sources of Degradable Thermoresponsive Hydrogels for Therapy

Gels 2020, 6(4), 42

Mahfoud Boustta and Michel Vert

 

ABSTRACT

One-pot free-radical polymerization of N-acryloyl glycinamide in the presence of hyaluronic acid as transfer-termination agent led to new copolymers in high yields without any chemical activation of hyaluronic acid before. All the copolymers formed thermoresponsive hydrogels of the Upper Critical Solution Temperature-type in aqueous media. Gel properties and the temperature of the reversible gel ↔ sol transition depended on feed composition and copolymer concentration. Comparison with mixtures of hyaluronic acid-poly(N-acryloyl glycinamide) failed in showing the expected formation of graft copolymers conclusively because poly(N-acryloyl glycinamide) homopolymers are also thermoresponsive. Grafting and formation of comb-like copolymers were proved after degradation of inter-graft hyaluronic acid segments by hyaluronidase. Enzymatic degradation yielded poly(N-acryloyl glycinamide) with sugar residues end groups as shown by NMR. In agreement with the radical transfer mechanism, the molar mass of these released poly(N-acryloyl glycinamide) grafts depended on the feed composition. The higher the proportion of hyaluronic acid in the feed, the lower the molar mass of poly(N-acryloyl glycinamide) grafts was. Whether molar mass can be made low enough to allow kidney filtration remains to be proved in vivo. Last but not least, Prednisolone was used as model drug to show the ability of the new enzymatically degradable hydrogels to sustain progressive delivery for rather long periods of time in vitro.DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

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

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

Modulation of protein release from penta-block copolymer microspheres European Journal of Pharmaceutics and Biopharmaceutics 152, 175–182 (2020)

European Journal of Pharmaceutics and Biopharmaceutics 152, 175–182 (2020).

Minh-Quan Le, Jean-Christophe Gimel, Xavier Garric, Thao-Quyen Nguyen-Pham, Cédric Paniagua, Jérémie Riou, Marie-Claire Venier-Julienne,

 

ABSTRACT

Releasing a protein according to a zero-order profile without protein denaturation during the polymeric microparticle degradation process is very challenging. The aim of the current study was to develop protein-loaded microspheres with new PLGA based penta-block copolymers for a linear sustained protein release. Lysozyme was chosen as model protein and 40 µm microspheres were prepared using the solid-in-oil-in-water solvent extraction/evaporation process. Two types of PLGA-P188-PLGA penta-block copolymers were synthetized with two PLGA-segments molecular weight (20 kDa or 40 kDa). The resulting microspheres (50P20-MS and 50P40-MS) had the same size, an encapsulation efficiency around 50–60% but different porosities. Their protein release profiles were complementary: linear but non complete for 50P40-MS, non linear but complete for 50P20-MS. Two strategies, polymer blending and microsphere mixing, were considered to match the release to the desired profile. The (1:1) microsphere mixture was successful. It induced a bi-phasic release with a moderate initial burst (around 13%) followed by a nearly complete linear release for 8 weeks. This study highlighted the potential of this penta-block polymer where the PEO block mass ratio influence clearly the Tg and consequently the microsphere structure and the release behavior at 37 °C. The (1:1) mixture was a starting point but could be finely tuned to control the protein release.

In Vivo Evaluation of the Efficacy and Safety of a Novel Degradable Polymeric Film for the Prevention of Intrauterine Adhesions.

Journal of Minimally Invasive Gynecology (2020)

Stéphanie Huberlant, Salomé Leprince, Lucie Allegre, Sophie Warembourg, Isabelle Leteuff, Hubert Taillades, Xavier Garric., Renaud de Tayrac, Vincent Letouzey.

ABSTRACT

To study the safety of a degradable polymeric film (DPF) and its efficacy on reducing the risk of intrauterine-adhesion (IUA) formation in a rat model.A series of case-control studies relying on random allocation, where feasible.The animal models comprised female and male Oncins France Strain A and female Wistar rats.The Oncins France Strain A rats were used for in vivo evaluation of the impact of the DPF on endometrial thickness and its effect on fertility. For in vivo evaluation of the biologic response, 40 Wistar rats were randomly allocated to intervention and control groups, with matched sampling time after surgery. Finally, for the in vivo evaluation of the DPF’s efficacy on IUA prevention, a total of 24 Wistar rats were divided into 3 groups: 1 treated with the DPF, 1 treated with hyaluronic acid gel, and a sham group. The DPF did not have a significant impact on endometrial thickness, and there were no significant differences in the number of conceived or prematurely terminated pregnancies, confirming its noninferiority to no treatment. The DPF did not induce irritation at 5 days and 28 days. Finally, the DPF significantly reduced the likelihood of complete IUA formation compared with hyaluronic acid gel– and sham-implanted animals, where only 27% of the animals had their uterine cavity obliterated compared with 80% and 100%, respectively.The DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

Hyaluronic Acid-Poly(N-acryloyl glycinamide) Copolymers as Sources of Degradable Thermoresponsive Hydrogels for Therapy

Gels 2020, 6(4), 42

Mahfoud Boustta and Michel Vert

 

ABSTRACT

One-pot free-radical polymerization of N-acryloyl glycinamide in the presence of hyaluronic acid as transfer-termination agent led to new copolymers in high yields without any chemical activation of hyaluronic acid before. All the copolymers formed thermoresponsive hydrogels of the Upper Critical Solution Temperature-type in aqueous media. Gel properties and the temperature of the reversible gel ↔ sol transition depended on feed composition and copolymer concentration. Comparison with mixtures of hyaluronic acid-poly(N-acryloyl glycinamide) failed in showing the expected formation of graft copolymers conclusively because poly(N-acryloyl glycinamide) homopolymers are also thermoresponsive. Grafting and formation of comb-like copolymers were proved after degradation of inter-graft hyaluronic acid segments by hyaluronidase. Enzymatic degradation yielded poly(N-acryloyl glycinamide) with sugar residues end groups as shown by NMR. In agreement with the radical transfer mechanism, the molar mass of these released poly(N-acryloyl glycinamide) grafts depended on the feed composition. The higher the proportion of hyaluronic acid in the feed, the lower the molar mass of poly(N-acryloyl glycinamide) grafts was. Whether molar mass can be made low enough to allow kidney filtration remains to be proved in vivo. Last but not least, Prednisolone was used as model drug to show the ability of the new enzymatically degradable hydrogels to sustain progressive delivery for rather long periods of time in vitro.DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

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:

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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