Micro & Nano Polymer and diagnostics Polymers for medical imaging Polymers for in vitro diagnostics

Polymer and diagnostics

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Polymers for medical imaging

MRI visible polymers for coatings and theranostic applications

About the project:

This project aims at offering chemical strategies that can help making the polymeric implants visible by the clinically relevant MRI procedures.For that, we focus on novel macromolecular MRI contrast agents that can be used as coatings, or as micro- and nanoparticles, and we focus on surface modification to make existing polymers MRI-visible.


Benjamin Nottelet
Benjamin Nottelet
Xavier Garric
Xavier Garric
Jean Coudane
Jean Coudane
Vincent Darcos
Vincent Darcos
Audrey Bethry
Audrey Bethry


Anita Shulz
Mira Younis
Sarah El Habnouni


Dr. Lemaire (MINT, Inserm 1066 – CNRS 6021), Dr. Franconi (platform PRISM), Prof. Letouzey (CHU Nîmes)


Campus France, Post-doctoral program UM, MENRT grant (ED 459), Chercheur d’Avenir 2013

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.


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.


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.

Controlled Anchoring of Iron Oxide Nanoparticles on Polymeric Nanofibers: Easy Access to Core@Shell Organic−Inorganic Nanocomposites for Magneto-Scaffolds

ACS Appl. Mater. Interfaces 11, 9519–9529 (2019)

Awada H., Al Samad A., Laurencin D., Gilbert R., Dumail X., El Jundi A., Bethry A., Pomrenke R., Johnson C., Lemaire L., Franconi F., Félix G., Larionova J., Guari Y., Nottelet B.


Composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and polymers are largely present in modern (bio)materials. However, while SPIONs embedded in polymer matrices are classically reported, the mechanical and degradation properties of the polymer scaffold are impacted by the SPIONs. Therefore, the controlled anchoring of SPIONs onto polymer surfaces is still a major challenge. Herein, we propose an efficient strategy for the direct and uniform anchoring of SPIONs on the surface of functionalized-polylactide (PLA) nanofibers via a simple free ligand exchange procedure to design PLA@SPIONs core@shell nanocomposites. The resulting PLA@SPIONs hybrid biomaterials are characterized by electron microscopy (SEM and TEM) and EDXS analysis, to probe the morphology and detect elements present at the organic/inorganic interface, respectively. A monolayer of SPIONs with a complete and homogeneous coverage is observed on the surface of PLA nanofibers. Magnetization experiments show that magnetic properties of the nanoparticles are well-preserved after their grafting on the PLA fibers and that the size of the nanoparticles does not change. The absence of cytotoxicity, combined with a high sensitivity of detection in MRI both in vitro and in vivo make these hybrid nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

UV-triggered photoinsertion of contrast agent onto polymer surfaces for in vivo MRI-visible medical devices

Multifunct. Mater. 2 0240012019 (2019)

Schulz A., Lemaire L., Bethry A.; Allegre L., Cardoso M., Bernex F., Franconi F., Goze-Bac C., Taillades H., Garric X., Nottelet B.


Polymeric materials are largely employed for the manufacturing of implants for various reasons, but they are typically invisible by conventional imaging methods. To improve surgical procedure and postoperative implant follow-up though, biomaterials are needed which allow an accurate and efficient imaging. Here, we present a direct and versatile strategy that allows to covalently immobilize T1 magnetic resonance imaging (MRI) contrast agents at the surface of various clinically relevant polymeric biomaterials. An aryl-azide bearing complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and gadolinium (Gd) has been synthesized for easy photografting onto polymer surfaces. Polycaprolactone (PCL), polylactide (PLA), polyurethane (PU), polyetheretherketone (PEEK) and polypropylene (PP) have been selected as clinically relevant substrates and successfully functionalized with the photosensitive MRI probe DOTA/Gd. Following in vitro assessment of their biocompatibility and MRI visibility, commercial MRI-visible PP hernia repair meshes (MRI-meshes) have been prepared. MRI-meshes have been implanted in rats for in vivo evaluation of their imaging capacities over 1 month. Histological evaluation and Gd biodistribution studies have been carried out confirming the potential of this straightforward approach to simply yield imageable medical devices.

X-ray visible polymers for implantable medical devices

About the project:

This project aims at offering chemical strategies that can help making the polymeric implants visible by the clinically relevant scanner procedures. For that, we focus on novel macromolecular MRI contrast agents that can be used as coatings, or as X-ray radiopaque agent to be formulated in medical devices.


Benjamin Nottelet
Benjamin Nottelet
Xavier Garric
Xavier Garric
Stéphane Dejean
Stéphane Dejean


Edouard Girard


Dr. Rhiele (University of Glasgow)), Dr. Chagnon & Prof .Favier (TIMC-IMAG, UMR 5525)


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


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.

Radiopaque poly(epsilon-caprolactone) as additive for X-ray imaging of temporary implantable medical devices

RSC Adv. 5, 84125–84133 (2015)

Samuel, R., Girard, E., Chagnon, G., Dejean, S., Favier, D., Coudane, J. & Nottelet, B



In this work we report on the synthesis of two hydrophobic and degradable gadolinium poly(ε-caprolactone) conjugates and their use for the preparation of MRI-visible nanoparticles intended for diagnosis applications. Advantage has been taken from functional poly(ε-caprolactone)s (PCL) bearing propargyl (PCL-yne) or amine groups (P(CL-co-NH2VL)) to yield conjugates by following two strategies. In a first approach, an azido-chelate of gadolinium (Gd(III)) has been conjugated by CuAAC to PCL-yne to yield a polymeric chelate containing 2.6 wt% of Gd(III). In a second approach, a dianhydride Gd(III)-ligand was reacted with P(CL-co-NH2VL) to yield, after complexation with Gd(III) salts, a polymeric chelate containing 15.4 wt% of Gd(III). The polymers biocompatibility was assessed against L929 fibroblasts. In a second part, advantage was taken from the PCLs conjugates hydrophobicity to easily prepare by nanoprecipitation nanoparticles with diameters ranging from 120 to 170 nm. The nanoparticles MRI-visibility was then evaluated and confirmed under the spin-echo and the clinically relevant gradient-echo MRI sequences.

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Aliphatic polyesters for medical imaging and theranostic applications

Eur. J. Pharm. Biopharm. 97, 350–370 (2015)

Nottelet, B., Darcos, V. & Coudane, J



Medical imaging is a cornerstone of modern medicine. In that context the development of innovative imaging systems combining biomaterials and contrast agents (CAs)/imaging probes (IPs) for improved diagnostic and theranostic applications focuses intense research efforts. In particular, the classical aliphatic (co)polyesters poly(lactide) (PLA), poly(lactide-co-glycolide) (PLGA) and poly(e-caprolactone) (PCL), attract much attention due to their long track record in the medical field. This review aims therefore at providing a state-of-the-art of polyester-based imaging systems. In a first section a rapid description of the various imaging modalities, including magnetic resonance imaging (MRI), optical imaging, computed tomography (CT), ultrasound (US) and radionuclide imaging (SPECT, PET) will be given.  Then, the two main strategies used to combine the CAs/IPs and the polyesters will be discussed. In more details we will first present the strategies relying on CAs/IPs encapsulation in nanoparticles, micelles, dendrimers or capsules. We will then present chemical modifications of polyesters backbones and/or polyester surfaces to yield macromolecular imaging agents. Finally, opportunities offered by these innovative systems will be illustrated with some recent examples in the fields of cell labeling, diagnostic or theranostic applications and medical devices.

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Jump to other polymer and diagnostics related subjects >>> Polymer and diagnostics >>>

Polymers for in vitro diagnostics

Project Biosensors

About the project:

Implantable biosensors for cancer biomarkers detection. The project is focused on the development of implantable biosensors based on polymer-peptide conjugate for cancer biomarkers detection.



Vincent Darcos
Vincent Darcos



Dr May Morris (Institut des Biomolécules Max Mousseron), Pr. Pascal Pujol (CHU Montpellier)


Key Initiative MUSE « Biomarkers & Therapy », Université de Montpellier

Nous recrutons un(e) Ingénieur(e) de recherche pour travailler sur la synthèse, la caractérisation et l’étude du suivi de dégradation in vivo de polymères dégradables utilisés dans le domaine biomédical.


Contexte : 

Dans le cadre des obligations réglementaires associées à la mise sur le marché d’un dispositif médical implantable ou d’un médicament injectable, l’évaluation de la dégradation des matériaux utilisés, l’identification des produits de dégradation et la question du devenir de ces produits de dégradation sont centrales en vue de l’obtention d’un marquage CE ou d’une autorisation de mise sur le marché. A ce jour, les dispositifs médicaux et les médicaments comportant des polymères comme le poly(acide lactique) (PLA) et le poly(éthylène glycol) (PEG) sont soumis à ces obligations. En effet, cette obligation est applicable à tout nouveau produit, même avec des polymères largement utilisés dans le domaine biomédical et approuvés par les agences de régulation (EMA, FDA etc…). Actuellement, les méthodes de suivi de dégradation des polymères en utilisant par exemple les méthodes de marquage avec des sondes radioactives ou fluorescentes sont limitées et présentent de nombreux inconvénients. Le projet BIOPOLTRACE vise à pallier ces limitations en permettant de réaliser un suivi de dégradation de copolymères PLA-PEG in vivo par le biais de méthodes analytiques de spectrométrie de masse de type Maldi-Tof et de chromatographie liquide couplée à la spectrométrie de masse (LC/MRM et LC 2D/MS). Les techniques proposées largement utilisés dans certains domaines apparaissent comme des méthodes innovantes dans le domaine visé (caractérisation et devenir des polymères pour la santé). De plus, le marquage isotopique au carbone 13 des espèces à étudier sera également proposé permettant notamment d’améliorer la sensibilité des techniques analytiques. Le marquage isotopique au 13C présente plusieurs avantages. Il utilise des isotopes du carbone non radioactifs permettant leur utilisation dans des laboratoires de chimie conventionnel. Il garantit le maintien de l’intégralité des propriétés physico-chimiques des polymères étudiés permettant ainsi de valider le suivi de dégradation in vivo des PLA-PEG sans interférer avec l’acide lactique non marqué 13C naturellement présent dans l’organisme.


Ce projet reposera sur la collaboration de 4 partenaires : la plateforme SynBio3 / Plateau Polymères de l’IBMM, le département des « Polymères pour la Santé et Biomatériaux » de l’IBMM (PHBM), le Pôle Protéome de Montpellier (PPM) et un partenaire industriel qui est un acteur majeur des thérapies innovantes par le biais d’implants injectables PLA-PEG.


Mission principale :

L’ingénieur(e) de Recherche à recruter sera en charge de la synthèse, la caractérisation et l’étude du suivi de dégradation in vivo de copolymères à base de poly(acide lactique) et de poly(éthylène glycol).


Activités :

-Synthèse et caractérisation de monomères de type dilactone marqué au carbone 13

-Synthèse et caractérisation de polymères dégradables à base de PLA et de PEG

-Mise au point de techniques analytiques en chromatographie liquide (SEC, HPLC, 2D LC) et en spectrométrie de masse (MALDI-Tof)

-Suivi de dégradation in vitro et vivo de polymères


Compétences / qualifications : 

Compétences : L’ingénieur(e) de Recherche à recruter devra avoir de fortes compétences en synthèse organique et en synthèse macromoléculaire. Il devra également maitriser les principales techniques de caractérisation de la chimie (macro)moléculaire : résonance magnétique nucléaire (RMN), chromatographie de type HPLC, chromatographie d’exclusion stérique (SEC), chromatographie préparative, spectroscopie de masse, calorimétrie différentielle (DSC), thermogravimétrie (TGA).

Qualifications / diplômes : Doctorat ou diplôme d’ingénieur reconnu par la CTI


Contactez Vincent Darcos

Nous recrutons un(e) Ingénieur(e) de recherche pour travailler sur la conception d’une matrice nanofibreuse dégradable pour promouvoir la réparation du disque intervertébral

  I.        Contexte :

Ce projet est le fruit de la collaboration entre trois équipes basées à Nantes, à Montpellier et à Ulm dont le savoir-faire est complémentaire : biologie, chimie des polymères et biomécanique. L’objectif globale de ce projet est d’élaborer une stratégie combinée à base de biomatériaux pour promouvoir la réparation du disque intervertébral et d’évaluer cette stratégie in vitro, ex vivo et à long terme in vivo chez la brebis. Dans ce cadre, nous souhaitons développer une matrice nanofibreuse dégradable et micro-structurée dont la composition et les propriétés mécaniques soient proches de celles du disque intervertébral.

Le travail aura lieu au sein de l’équipe PHBM (Polymers for Health and Biomaterial) Institut des Biomolécules Max Mousseron, UMR CNRS 5247, Pôle Chimie Balard Recherche, 1919, route de Mende 34293 MONTPELLIER cedex 5

Notre équipe est spécialisée dans la synthèse de polymères pour la santé et s’intéresse en particulier aux polymères dégradables pour la régénération des tissus mous.

CDD de droit public de 18 mois – Début : janvier/février 2022

II.        Mission principale :

L’ingénieur(e) à recruter sera en charge du développement des matrices nanofibreuses dégradables et micro-structurées support de la régénération du disque intervertébral.

III.        Activités :

Afin de répondre à cette problématique nous envisageons :

  • De synthétiser de nouveaux copolymeres dégradables par polymérisation par ouverture de cycle
  • De produire des nanofibres par electrospining et de les assembler pour obtenir un scaffold 3D
  • D’évaluer les propriétés biologiques
  • D’évaluer l’impact de la stérilisation sur les propriétés de dégradation, mécaniques et morphologiques
IV.     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 ainsi qu’être communicante. La/le candidat(e) devra avoir de l’expérience à l’interface chimie/biologie.

  • Qualifications / diplômes : Bac+3 exigé
  • Expérience : Avoir de l’expérience à l’interface de la chimie/biologie.

Liste des compétences souhaitées :

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

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

Contacts :

Dr Coline PINESE & Pr Xavier GARRIC et

Date limite de candidature:  31 decembre 2021

Electrospun microstructured PLA-based scaffolds featuring relevant anisotropic, mechanical and degradation characteristics for soft tissue engineering

Materials Science and Engineering: C Volume 129, October 2021, 112339

Louis Gangolphe, Christopher Y.Leon Valdivieso, Benjamin Nottelet, Stéphane Déjean, Audrey Bethry, Coline Pinese, Frédéric Bossard and Xavier Garric


Electrospun scaffolds combine suitable structural characteristics that make them strong candidates for their use in tissue engineering. These features can be tailored to optimize other physiologically relevant attributes (e.g. mechanical anisotropy and cellular affinity) while ensuring adequate degradation rates of the biomaterial. Here, we present the fabrication of microstructured scaffolds by using a combination of micropatterned electrospinning collectors (honeycomb- or square-patterned) and poly(lactic acid) (PLA)-based copolymers (linear or star-shaped). The resulting materials showed appropriate macropore size and fiber alignment that were key parameters to enhance their anisotropic properties in protraction. Moreover, their elastic modulus, which was initially similar to that of soft tissues, gradually changed in hydrolytic conditions, matching the degradation profile in a 2- to 3-month period. Finally, honeycomb-structured scaffolds exhibited enhanced cellular proliferation compared to standard electrospun mats, while cell colonization was shown to be guided by the macropore contour. Taking together, these results provide new insight into the rational design of microstructured materials that can mimic the progressive evolution of properties in soft tissue regeneration

Star-poly(lactide)-peptide hybrid networks as bioactive materials


European Polymer Journal Volume 139, 5 October 2020, 109990

L.V. Arsenie, C. Pinese, A. Bethry, L. Valot, P. Verdie, B. Nottelet, G. Subra, V. Darcos, X. Garric


Abstract Poly(lactide) (PLA) is a widely used biomaterial in many biomedical applications. However, it is inert and therefore lacks bioactivity, which is a major drawback in addressing tissue regeneration issues. This work aims to develop new implantable biomaterials composed of PLAs functionalized with bioactive peptides. For that purpose, we set up an original synthesis based on star-PLA bearing triethoxysilyl propyl groups (PLA-PTES) and bifunctional silylated peptides that react together via sol-gel process to create a bioactive network. We demonstrate that the molecular weight of the PLA and the quantity of peptide have a large influence on the crosslinking efficiency, the mechanical properties and the biodegradability of the resulting materials. The presence of peptide increases the crosslinking efficiency of the networks resulting in more rigid networks with stable mechanical properties up to 8 weeks. At last, the potential of this new type of hybrid biomaterials for soft tissue engineering was demonstrated through cells adhesion assays that showed a significant enhancement of fibroblasts adhesion

Star-poly(lactide)-peptide hybrid networks as bioactive materials

Star-poly(lactide)-peptide hybrid networks as bioactive materials

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