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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:

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

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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

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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:

Coraline Chartier
Coraline Chartier

Collaborations:

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

Funding:

CNRS interdisciplinary PhD program

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)

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

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Acta Biomaterialia. In press, (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

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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

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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

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

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

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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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