Benjamin Nottelet

Benjamin Nottelet

Professor, Faculty of pharmacy, University of Montpellier

Benjamin initially graduated as a chemical engineer from the Ecole Nationale Supérieure de Chimie of Montpellier (ENSCM), France before completing an industrial PhD on degradable polymers from the University of Montpellier (UM) in 2005 in contract with RHODIA in the group of Prof. Vert. He then worked in the Macromolecular Engineering and Architectures group of ENSCM in the group of Prof. Boutevin before joining the Department of Pharmaceutics and Biopharmaceutics of Prof. Gurny at the University of Geneva (UNIGE) to develop scaffolds for tissue engineering and drug delivery systems. In 2008, he became Associate Professor in the Faculty of Pharmacy at UM and joined the Department of Artificial Biopolymers of IBMM of Prof. Coudane, where he was appointed Full Professor in 2018.  His research activities focus on the synthesis and modification of degradable polymers for advanced biomedical applications and include hybrid biomaterials, bioactive surfaces, and multifunctional polymers.

Part of his recent work focuses on the synthesis and design of (1) innovative multifunctional degradable polymers for use in the field of drug delivery with smart and stimuli-responsive systems or (2) macromolecular contrast agents in the field of diagnostic allowing for MRI or X-ray imaging in of medical devices, or of theranostic approaches.

Another part of his research focuses on (3) hybrid biomaterials including peptide-based polymers or nanocomposites,  and degradable elastomers for tissue engineering applications, as well as the development of  (4) surface modification strategies to yield active surfaces in the frame of antibacterial and of imaging applications.

Benjamin is member of the editorial board of Multifunctional Materials and is co-author of over 70 papers and 3 patents.


Orcid n°: 0000-0002-8577-9273

5  recent papers :

A. El Jundi, M. Morille, N. Bettache, A. Bethry, J. Berthelot, J. Salvador, S. Hunger, Y. Bakkour, E. Belamie, B. Nottelet. Degradable double hydrophilic block copolymers and tripartite polyionic complex micelles thereof for small interfering ribonucleic acids (siRNA) delivery J. Colloid. Interface Sci. 2020,580, 449.

Girard E., Chagnon G., Broisat A., Dejean S., Soubies A., Gil H., Sharkawi T., Boucher F. Roth G.S., Trilling B., Nottelet B.From in vitro evaluation to human post-mortem pre-validation of a radiopaque and resorbable internal biliary stent for liver transplantation applications. Acta Biomater. 2020, 106, 66.

Hussein Awada, Assala Al Samad, Danielle Laurencin,* Ryan Gilbert, Xavier Dumail, Ayman El Jundi, Audrey Bethry, Rebecca Pomrenke, Christopher Johnson, Laurent Lemaire, Florence Franconi, Gautier Félix, Joulia Larionova, Yannick Guari, Benjamin Nottelet*, Controlled Anchoring of Iron Oxide Nanoparticles on Polymeric Nanofibers: Easy Access to Core@Shell Organic−Inorganic Nanocomposites for Magneto-Scaffolds ACS Appl. Mater. Interfaces 2019, 11, 9519.

Anita Schulz, Laurent Lemaire, Audrey Bethry, Lucie Allègre, Maïda Cardoso, Florence Bernex, Florence Franconi, Christophe Goze-Bac, Hubert Taillades, Xavier Garric, Benjamin Nottelet. UV-triggered photoinsertion of contrast agent onto polymer surface for in vivo MRI-visible medical devices. Multifunctional Materials 2019, 2, 0240012019.

Louis Gangolphe, Stéphane Déjean, Audrey Bethry, Sylvie Hunger, Coline Pinese, Xavier Garric, Frédéric Bossard, Benjamin Nottelet. Degradable multi(aryl-azide) star copolymer as universal photo-crosslinker for elastomeric scaffolds Mat. Today Chem. 2019, 12, 209.

Dual-crosslinked degradable elastomeric networks with self-healing properties: bringing multi(catechol) star block copolymers into play

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ACS Appl. Mater. Interfaces 15, 2077-2091 (2023)

Mathilde Grosjean, Louis Gangolphe, Stéphane Dejean, Sylvie Hunger, Audrey Bethry, Frédéric Bossard, Xavier Garric, Benjamin Nottelet


In the biomedical field, degradable chemically crosslinked elastomers are interesting materials for tissue engineering applications since they present rubber-like mechanical properties matching with those of soft tissues and are able to preserve their 3D structure over degradation. Their use in biomedical applications requires surgical handling and implantation that can be source of accidental damages responsible for loss of properties. Therefore, their inability to be healed after damage or breaking can be a major drawback. In this work, biodegradable dual-crosslinked networks that exhibit fast and efficient self-healing properties at 37 °C are designed. Self-healable dual-crosslinked (chemically and physically) elastomeric networks are prepared from two methods. The first approach is based on the mix of hydrophobic PEG-PLA star-shaped copolymers functionalized either with catechol or methacrylate moieties. In the second approach, hydrophobic bifunctional PEG-PLA star-shaped copolymers with both catechol and methacrylate on their structure are used. In the two systems the supramolecular network is responsible for the self-healing properties thanks to the dynamic dissociation/re-association of the numerous hydrogen bonds between the catechol groups, whereas the covalent network ensures mechanical properties similar to pure methacrylate networks. The self-healable materials display mechanical properties that are compatible with soft tissues and exhibit linear degradation because of the chemical crosslinks. The performances of networks from mix copolymers vs. bifunctional copolymers are compared and demonstrate the superiority of the later. The biocompatibility of the materials is also demonstrated and confirm the potential of these degradable self-healable elastomeric networks to be used for the design of temporary medical devices.

Degradable Bioadhesives Based on Star PEG–PLA Hydrogels for Soft Tissue Applications

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Biomacromolecules XX, XX (2022)

Mathilde Grosjean, Edouard Girard, Audrey Bethry, Grégory Chagnon, Xavier Garric, Benjamin Nottelet


Tissue adhesives are interesting materials for wound treatment as they present numerous advantages compared to traditional methods of wound closure such as suturing and stapling. Nowadays, fibrin and cyanoacrylate glues are the most widespread commercial biomedical adhesives, but these systems display some drawbacks. In this study, degradable bioadhesives based on PEG–PLA star-shaped hydrogels are designed. Acrylate, methacrylate, and catechol functional copolymers are synthesized and used to design various bioadhesive hydrogels. Various types of mechanisms responsible for adhesion are investigated (physical entanglement and interlocking, physical interactions, chemical bonds), and the adhesive properties of the different systems are first studied on a gelatin model and compared to fibrin and cyanoacrylate references. Hydrogels based on acrylate and methacrylate reached adhesion strength close to cyanoacrylate (332 kPa) with values of 343 and 293 kPa, respectively, whereas catechol systems displayed higher values (11 and 19 kPa) compared to fibrin glue (7 kPa). Bioadhesives were then tested on mouse skin and human cadaveric colonic tissue. The results on mouse skin confirmed the potential of acrylate and methacrylate gels with adhesion strength close to commercial glues (15–30 kPa), whereas none of the systems led to high levels of adhesion on the colon. These data confirm that we designed a family of degradable bioadhesives with adhesion strength in the range of commercial glues. The low level of cytotoxicity of these materials is also demonstrated and confirm the potential of these hydrogels to be used as surgical adhesives.

Poly(ε-caprolactone)-Based Graft Copolymers: Synthesis Methods and Applications in the Biomedical Field: A Review

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Molecules 27, 7339 (2022)

 Jean Coudane, Benjamin Nottelet, Julia Mouton, Xavier Garric, Hélène Van Den Berghe


Synthetic biopolymers are attractive alternatives to biobased polymers, especially because they rarely induce an immune response in a living organism. Poly ε-caprolactone (PCL) is a well-known synthetic aliphatic polyester universally used for many applications, including biomedical and environmental ones. Unlike poly lactic acid (PLA), PCL has no chiral atoms, and it is impossible to play with the stereochemistry to modify its properties. To expand the range of applications for PCL, researchers have investigated the possibility of grafting polymer chains onto the PCL backbone. As the PCL backbone is not functionalized, it must be first functionalized in order to be able to graft reactive groups onto the PCL chain. These reactive groups will then allow the grafting of new reagents and especially new polymer chains. Grafting of polymer chains is mainly carried out by “grafting from” or “grafting onto” methods. In this review we describe the main structures of the graft copolymers produced, their different synthesis methods, and their main characteristics and applications, mainly in the biomedical field.

Bioresorbable bilayered elastomers/hydrogels constructs with gradual interfaces for the fast actuation of self-rolling tubes

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ACS Appl. Mater. Interfaces 14, 43719–43731 (2022)

Mathilde Grosjean, Sidzigui Ouedraogo, Stéphane Déjean, Xavier Garric, Valeriy Luchnikov, Arnaud Ponche, Noëlle Mathieu, Karine Anselme, Benjamin Nottelet

Degradable fast self-rolling biomaterials


In the biomedical field, self-rolling materials provide interesting opportunities to develop medical devices suitable for drug or cell encapsulation. However, to date a major limitation for medical applications is the use of non-biodegradable and non-biocompatible polymers that are often reported for such applications, or the slow actuation witnessed with degradable systems. In this work, biodegradable self-rolling tubes that exhibit a spontaneous and rapid actuation when immersed in water are designed. Photo-crosslinkable hydrophilic and hydrophobic PEG-PLA star-shaped copolymers are prepared and used to prepare bilayered constructs. Thanks to the discrete mechanical and swelling properties of each layer and the cohesive/gradual nature of the interface, the resulting bilayered films are able to self-roll in water in less than 30 seconds depending on the nature of the hydrophilic layer and on the shape of the sample. The cytocompatibility and degradability of the materials are demonstrated and confirm the potential of such self-rolling resorbable biomaterials in the field of temporary medical devices.

Polyester-polydopamine copolymers for intravitreal drug delivery: role of polydopamine drug-binding properties on extending drug release

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Biomacromolecules 23, 4388-4400, (2022)

Floriane Bahuon, Vincent Darcos, Sulabh Patel, Zana Marin, Jean Coudane, Grégoire Schwach, and Benjamin Nottelet


PCL-g-PDA drug binding copolymer


This work reports on a novel polyester copolymer containing poly(dopamine), a synthetic analogue of natural melanin, evaluated in sustained-release drug delivery system for ocular intravitreal administration of drugs. More specifically, a graft copolymer of poly(ε-caprolactone)-graft-poly(dopamine) (PCL-g-PDA) has been synthesized, and was shown to further extend the drug release benefits of state-of-the-art biodegradable intravitreal implants made of poly(lactide) and poly(lactide-co-glycolide). The innovative biomaterial combines the documented drug-binding properties of melanin naturally present in the eye, with the established ocular tolerability and biodegradation of polyester implants. The PCL-g-PDA copolymer was obtained by a two-step modification of PCL with a final PDA content around 2-3 wt.%, and was fully characterised by SEC, NMR, and DOSY NMR. The thermoplastic nature of PCL-g-PDA allowed its simple processing by hot-melt compression moulding to prepare small implants. The properties of unmodified PCL and PCL-g-PDA implants were studied and compared in terms of thermal properties (DSC), thermal stability (TGA), degradability and in vitro cytotoxicity. PCL and PCL-g-PDA implants exhibited similar degradation properties in vitro and were both stable under physiological conditions over 110 days. Likewise, both materials were non-cytotoxic towards L929 and ARPE-19 cells. The drug-loading and in vitro release properties of the new materials were investigated with dexamethasone (DEX) and ciprofloxacin hydrochloride (CIP) as representative drugs featuring low and high melanin binding affinities, respectively. In comparison to unmodified PCL, PCL-g-PDA implants showed significant extension of drug release most likely because of specific drug-catechol interaction with the PDA moieties of the copolymer. The present study confirms the advantages of designing PDA-containing polyesters as a class of biodegradable and biocompatible thermoplastics that can modulate and remarkably extend drug release kinetics thanks to their unique drug binding properties, especially, but not limited to, for ocular applications.

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Design of Hybrid Polymer Nanofiber/Collagen Patches Releasing IGF and HGF to Promote Cardiac Regeneration

Pharmaceutics 2022, 14, 1854

Eloise Kerignard, Audrey Bethry, Chloé Falcoz, Benjamin Nottelet and Coline Pinese



Cardiovascular diseases are the leading cause of death globally. Myocardial infarction in particular leads to a high rate of mortality, and in the case of survival, to a loss of myocardial functionality due to post-infarction necrosis. This functionality can be restored by cell therapy or biomaterial implantation, and the need for a rapid regeneration has led to the development of bioactive patches, in particular through the incorporation of growth factors (GF). In this work, we designed hybrid patches composed of polymer nanofibers loaded with HGF and IGF and associated with a collagen membrane. Among the different copolymers studied, the polymers and their porogens PLA-Pluronic-PLA + PEG and PCL + Pluronic were selected to encapsulate HGF and IGF. While 89 and 92% of IGF were released in 2 days, HGF was released up to 58% and 50% in 35 days from PLA-Pluronic-PLA + PEG and PCL + Pluronic nanofibers, respectively. We also compared two ways of association for the loaded nanofibers and the collagen membrane, namely a direct deposition of the nanofibers on a moisturized collagen membrane (wet association), or entrapment between collagen layers (sandwich association). The interfacial cohesion and the degradation properties of the patches were evaluated. We also show that the sandwich association decreases the burst release of HGF while increasing the release efficiency. Finally, we show that the patches are cytocompatible and that the presence of collagen and IGF promotes the proliferation of C2C12 myoblast cells for 11 days. Taken together, these results show that these hybrid patches are of interest for cardiac muscle regeneration.

Peptide-guided self-assembly of polyethylene glycol-b-poly(ε-caprolactone-g-peptide) block copolymers

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Eur. Pol. J. 176, 111386 (2022)

Ayman El Jundi, Matthias Mayor, Enrique Folgado, Chaimaa Gomri, Belkacem Tarek Benkhaled, Arnaud Chaix, Pascal Verdie, Benjamin Nottelet, Mona Semsarilar


Biodegradable poly(ethylene glycol)-b-poly(ε-caprolactone-g-peptide) (PEG-b-PCL-g-peptide) copolymers were synthesized using a combination of ring opening  polymerization and thiol-yne photoaddition of peptides on the alkyne functional PCL block. The peptides Phe-Phe, Tyr-Tyr and Arg-Gly-Asp were selected based on the expected interactions (Pi-stacking, H-bonding, electrostatic). The self-assembly of these copolymers was studied via testing the effect of various parameters such as the nature of the solvent and non-solvant as well as their ratio,mixing method, temperature and concentration. Structures obtained by varying these parameters were characterised using transmission electron microscopy (TEM) and dynamic light scattering (DLS). Spherical and lamellar structures (oval leaf-shaped) of different sizes were identified as a function of the conditions. The role of the crystallisation and of the peptides was highlighted with more defined and stable structures obtained for Tyr-Tyr functional copolymers.

Poly(Lactic Acid)-Based Graft Copolymers: Syntheses Strategies and Improvement of Properties for Biomedical and Environmentally Friendly Applications – A Review

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Molecules 27, 4135 (2022)

 Jean Coudane , Hélène Van Den Berghe, Julia Mouton, Xavier Garric, Benjamin Nottelet


As a potential replacement for petroleum-based plastics, biodegradable bio-based polymers such as poly(lactic acid) (PLA) have received much attention in recent years. PLA is a biodegradable polymer with major applications in packaging and medicine. Unfortunately, PLA is less flexible and has less impact resistance than petroleum-based plastics. To improve the mechanical properties of PLA, PLA-based blends are very often used, but the outcome does not meet expectations because of the non-compatibility of the polymer blends. From a chemical point of view, the use of graft copolymers as a compatibilizer with a PLA backbone bearing side chains is an interesting option for improving the compatibility of these blends, which remains challenging. This review article reports on the various graft copolymers based on a PLA backbone and their syntheses following two chemical strategies: the synthesis and polymerization of modified lactide or direct chemical post-polymerization modification of PLA. The main applications of these PLA graft copolymers in the environmental and biomedical fields are presented.

Tuning the properties of porous chitosan: Aerogels and cryogels

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Int. J. Biol. Macromol. 202, 215–223 (2022)

Coraline Chartier, Sytze Buwalda, Hélène Van Den Berghe, Benjamin Nottelet, Tatiana Budtova


Highly porous chitosan-based materials were prepared via dissolution, non-solvent induced phase separation and drying using different methods. The goal was to tune the morphology and properties of chitosan porous materials by varying process parameters. Chitosan concentration, concentration of sodium hydroxide in the coagulation bath and aging time were varied. Drying was performed via freeze-drying leading to “cryogels” or via drying with supercritical CO2 leading to “aerogels”. Cryogels were of lower density than aerogels (0.03–0.12 g/cm3 vs 0.07–0.26 g/cm3, respectively) and had a lower specific surface area (50–70 vs 200–270 m2/g, respectively). The absorption of simulated wound exudate by chitosan aerogels and cryogels was studied in view of their potential applications as wound dressing. Higher absorption was obtained for cryogels (530–1500%) as compared to aerogels (200–610%).

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