K. Glinel - Academia.edu (original) (raw)
Papers by K. Glinel
Acta Biomaterialia, 2018
Porous polymeric microcarriers are a versatile class of biomaterial constructs with extensive use... more Porous polymeric microcarriers are a versatile class of biomaterial constructs with extensive use in drug delivery, cell culture and tissue engineering. Currently, most methods for their production require potentially toxic organic solvents with complex setups which limit their suitability for biomedical applications and their large-scale production. Herein, we report an organic, solvent-free method for the fabrication of porous poly(L-lactide) (PLLA) microcarriers. The method is based on the spherulitic crystallization of PLLA in its miscible blends with poly(ethylene glycol) (PEG). It is shown that the PLLA spherulites are easily recovered as microcarriers from the blends by a water-based process. Independent control over microcarrier size and porosity is demonstrated, with a higher crystallization temperature leading to a larger size, and a higher PLLA content in the starting blend resulting in a lower microcarrier porosity. Microcarriers are shown to be biocompatible for the culture of murine myoblasts and human adipose stromal/stem cells (hASC). Moreover, they support not only the longterm proliferation of both cell types but also hASC differentiation toward osseous tissues. Furthermore, while no significant differences are observed during cell proliferation on microcarriers of two different porosities, microcarriers of lower porosity induce a stronger hASC osteogenic differentiation, as evidenced by higher ALP enzymatic activity and matrix mineralization. Consequently, the proposed organic-solvent-free method for the fabrication of biocompatible porous PLLA microcarriers represents an innovative methodology for ex vivo cell expansion and its application in stem cell therapy and tissue engineering. Statement of Significance We report a new solvent-free method for the preparation of porous polymeric microcarriers for cell culture, based on biocompatible poly(L-lactide), with independently controllable size and porosity. This approach, based on the spherulitic crystallization in polymer blends, offers the advantages of simple implementation, biological and environmental safety, easy adaptability and up-scalablility. The suitability of these microcarriers is demonstrated for long-term culture of both murine myoblasts and human adipose stromal/stem cells (hASCs). We show that prepared microcarriers support the osteogenic differentiation of hASCs, provided microcarriers of properly-tuned porosity are used. Hence, this new method is an important addition to the arsenal of microcarrier fabrication techniques, which will contribute to the adoption, regulatory approval and eventually clinical availability of microcarrier-based treatments and therapies.
Langmuir, 2004
We present a new way to protect polyelectrolyte multilayers from water, consisting in the adsorpt... more We present a new way to protect polyelectrolyte multilayers from water, consisting in the adsorption and subsequent fusing of charged wax particles atop a multilayer. The formation of the wax layer is demonstrated by different techniques such as ellipsometry, contact angle measurements, and atomic force microscopy. The diffusion of water in protected and unprotected multilayers is studied by in situ neutron reflectometry. Whereas a top layer of wax crystals already allows substantial reduction of the diffusion, the fusion of this top layer leads to the dominating exclusion of water from the multilayers when dipped in water. This method opens up new interesting avenues for polyelectrolyte multilayers in practical applications where permeability of water, ions, or hydrophilic drugs is an issue.
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2007
In this review we summarize novel aspects of the hydration and internal properties of polyelectro... more In this review we summarize novel aspects of the hydration and internal properties of polyelectrolyte multilayers formed by layer-by-layer assembly. Reflectivity techniques monitor the water content and swelling behavior, while spin relaxation monitors water mobility. Odd-even effects in dependence on the number of layers are discussed in terms of an influence of the terminating layer. Other novel methodological approaches like X-ray microscopy or NMR cryoporometry address the water content in hollow capsules, and the water pore size distribution, respectively. Multilayer material properties are relevant for different applications. As a novel concept, dielectric properties are monitored in a field effect transistor device. Ion mobility and redox processes in multilayers are revealed by the electrochemical properties. Mechanical properties of multilayers, studied by colloidal probe atomic force microscopy depend on the conformation of the polymers involved.
The formation of ultrathin polymer films by successive adsorption of polyelectrolytes of opposite... more The formation of ultrathin polymer films by successive adsorption of polyelectrolytes of opposite charge has been extensively studied from 1992 on. In all reported cases where organic polyelectrolytes have been used, the profuse intermixing which exists between subsequent layers results in virtually structureless films. However, we have recently discovered a possibility to obtain internally-structured films, by using polyelectrolytes of reduced
IFMBE Proceedings, 2014
Biomaterials aim to mimic in vivo extracellular matrices where cell interactions occur on the nan... more Biomaterials aim to mimic in vivo extracellular matrices where cell interactions occur on the nanoscale. Thus, incorporation of nanosized components is interesting in the preparation of bioactive surfaces. We present a technique using nanoimprint lithography to create chemical nanopatterns on silicon surfaces functionalized with bioactive motifs. Due to high throughput and versatility, a wide range of geometries and dimensions can be efficiently patterned. In our study, we prepared and characterized two types of bioactive nanodots (150 nm diameter with 350 nm spacing, and 80 nm diameter with 110 nm spacing) functionalized with cell adhesion-promoting RGD peptides. We examined mesenchymal stem cell adhesion and commitment on these modified material surfaces with respect to homogeneous RGD and non-functionalized surfaces. We report that bioactive nanostructures induce fibrillar adhesions on human mesenchymal stem cells with an impact on their behavior and dynamics specifically in terms of cell spreading, cell-material contact, and cell differentiation.
Polymer, 1999
New hydrophobically modified pullulans were synthesized in two ways: (i) neutral derivatives (HMP... more New hydrophobically modified pullulans were synthesized in two ways: (i) neutral derivatives (HMPFs) obtained by direct esterification of pullulan with a perfluoroalkyl carboxylic acid (C 8 F 17 CH 2 CH 2 COOH), and (ii) ionic derivatives (HMCMPs) obtained by amidation of carboxymethylpullulan with two perfluoroalkylamines (C 7 F 15 CH 2 NH 2 and C 8 F 17 CH 2 CH 2 NH 2). The molar hydrophobe contents ranged from 1.1 to 4.8% with respect to the anhydroglucose units. Associative properties in aqueous solutions were studied by rheological and sizeexclusion chromatography/light-scattering measurements. In dilute solution, the polymers form intermolecular aggregates with a more compact conformation than that of precursors. In semi-dilute solution, the ionic derivatives are more viscosifying than neutral because of their better solubility. This effect is significant as the alkylperfluorinated chain length increases.
Sensors and Actuators B: Chemical, 2012
Screen-printed carbon electrodes were modified with polyaniline by electrochemical oxidation to p... more Screen-printed carbon electrodes were modified with polyaniline by electrochemical oxidation to produce a potentiometric pH transducer. The resulting pH sensor exhibited a fast, reproducible and sensitive potentiometric response of approximately 59 mV per pH unit from pH 4 to 8. The pH sensor response was found to be stable in time for up to one month. Such potentiometric response was obtained for thick polyaniline films. Thinner polymer films exhibited less sensitive responses and were found to have a smaller lifetime. The sensitivity of polyaniline to pH variations was then used to design an enzymatic biosensor. For that purpose, urease was immobilized on a polyelectrolyte multilayer film (PEM), obtained by the alternate deposition of charged polysaccharides (layer-by-layer assembly, LbL), over the polyaniline film. Covalent grafting of the urease enzyme to the PEM film was also tested using carbodiimide coupling reaction. The potentiometric response of this assembly to pH variations was similar to the one of polyaniline films, and its response to urea, from 10 −4 to 10 −1 mol L −1 , exhibited a very high sensitivity combined to fast response, good lifetime and reproducibility. The number of polyelectrolyte layers composing the PEM film was also found to affect the response of the urea sensors.
Sequential Assembly of Nanocomposite Materials, 2012
ABSTRACT This chapter contains sections titled: * Introduction * Polyelectrolyte Films Incorporat... more ABSTRACT This chapter contains sections titled: * Introduction * Polyelectrolyte Films Incorporating Randomly Distributed Hydrophobic Nanodomains for Antimicrobial Applications * Multicompartmentalized Strati.ed Polyelectrolyte Films for Control of Energy Transfer * Conclusions and Perspectives * References
Electrochimica Acta, 2014
ABSTRACT Elaboration of original polymer materials using self-assembly and electrochemistry.•In s... more ABSTRACT Elaboration of original polymer materials using self-assembly and electrochemistry.•In situ monitoring of the growth of the polymer materials.•Development of urea electrochemical sensors using a home-made mini-potentiostat.
Multilayer Thin Films, 2002
Le pullulane est un polysaccharide de fermentation neutre caracterise par un squelette macromolec... more Le pullulane est un polysaccharide de fermentation neutre caracterise par un squelette macromoleculaire flexible. La presence de trois fonctions alcool par motif anhydroglucose a permis de le modifier chimiquement de facon a obtenir des composes associatifs porteurs de chainons perfluores. Des derives neutres ont d'abord ete synthetises par fixation d'un acide carboxylique C11 (< 4%) sur les fonctions hydroxyle. Cependant, ces echantillons ne presentent pas de proprietes viscosifiantes marquees par rapport au precurseur en raison d'une mauvaise solvatation des chaines macromoleculaires. Afin de renforcer l'hydrophilie du pullulane et permettre une bonne solubilisation des derives amphiphiles, des groupes carboxymethyle ont ete introduits sur le squelette polysaccharidique. Une etude RMN ( 1H et 13C) a montre que la substitution s'effectue principalement sur le carbone 3 et que la fonction hydroxyle situee sur le carbone 4 est la plus reactive vis-a-vis de la substitution. Les carboxymethylpullulanes (0,85 ≤ DS c o o ≤ 1) ont ensuite ete hydrophobises par greffage d'amines (2,5 a 7%) de longueur variable (C 8 a C 1 3) sur les fonctions acide carboxylique. Lors de cette synthese, une reaction secondaire entrainant la reticulation partielle du polymere apparait. En ajustant les conditions experimentales, des echantillons amphiphiles non reticules et partiellement reticules ont ete prepares. Les derives non reticules presentent des proprietes en solution classiques des polymeres associatifs du fait de l'etablissement de nombreuses associations hydrophobes intra et/ou intermoleculaires. Les proprietes viscosifiantes de ces composes sont fonction de parametres moleculaires (concentration en polymere, taux de greffage, longueur du greffon,) et de parametres exterieurs (force ionique, tensioactif,). Dans le cas des polymeres reticules, on obtient des microgels et les echantillons presentent un comportement typique d'une suspension.
Acta Biomaterialia, 2018
Porous polymeric microcarriers are a versatile class of biomaterial constructs with extensive use... more Porous polymeric microcarriers are a versatile class of biomaterial constructs with extensive use in drug delivery, cell culture and tissue engineering. Currently, most methods for their production require potentially toxic organic solvents with complex setups which limit their suitability for biomedical applications and their large-scale production. Herein, we report an organic, solvent-free method for the fabrication of porous poly(L-lactide) (PLLA) microcarriers. The method is based on the spherulitic crystallization of PLLA in its miscible blends with poly(ethylene glycol) (PEG). It is shown that the PLLA spherulites are easily recovered as microcarriers from the blends by a water-based process. Independent control over microcarrier size and porosity is demonstrated, with a higher crystallization temperature leading to a larger size, and a higher PLLA content in the starting blend resulting in a lower microcarrier porosity. Microcarriers are shown to be biocompatible for the culture of murine myoblasts and human adipose stromal/stem cells (hASC). Moreover, they support not only the longterm proliferation of both cell types but also hASC differentiation toward osseous tissues. Furthermore, while no significant differences are observed during cell proliferation on microcarriers of two different porosities, microcarriers of lower porosity induce a stronger hASC osteogenic differentiation, as evidenced by higher ALP enzymatic activity and matrix mineralization. Consequently, the proposed organic-solvent-free method for the fabrication of biocompatible porous PLLA microcarriers represents an innovative methodology for ex vivo cell expansion and its application in stem cell therapy and tissue engineering. Statement of Significance We report a new solvent-free method for the preparation of porous polymeric microcarriers for cell culture, based on biocompatible poly(L-lactide), with independently controllable size and porosity. This approach, based on the spherulitic crystallization in polymer blends, offers the advantages of simple implementation, biological and environmental safety, easy adaptability and up-scalablility. The suitability of these microcarriers is demonstrated for long-term culture of both murine myoblasts and human adipose stromal/stem cells (hASCs). We show that prepared microcarriers support the osteogenic differentiation of hASCs, provided microcarriers of properly-tuned porosity are used. Hence, this new method is an important addition to the arsenal of microcarrier fabrication techniques, which will contribute to the adoption, regulatory approval and eventually clinical availability of microcarrier-based treatments and therapies.
Langmuir, 2004
We present a new way to protect polyelectrolyte multilayers from water, consisting in the adsorpt... more We present a new way to protect polyelectrolyte multilayers from water, consisting in the adsorption and subsequent fusing of charged wax particles atop a multilayer. The formation of the wax layer is demonstrated by different techniques such as ellipsometry, contact angle measurements, and atomic force microscopy. The diffusion of water in protected and unprotected multilayers is studied by in situ neutron reflectometry. Whereas a top layer of wax crystals already allows substantial reduction of the diffusion, the fusion of this top layer leads to the dominating exclusion of water from the multilayers when dipped in water. This method opens up new interesting avenues for polyelectrolyte multilayers in practical applications where permeability of water, ions, or hydrophilic drugs is an issue.
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2007
In this review we summarize novel aspects of the hydration and internal properties of polyelectro... more In this review we summarize novel aspects of the hydration and internal properties of polyelectrolyte multilayers formed by layer-by-layer assembly. Reflectivity techniques monitor the water content and swelling behavior, while spin relaxation monitors water mobility. Odd-even effects in dependence on the number of layers are discussed in terms of an influence of the terminating layer. Other novel methodological approaches like X-ray microscopy or NMR cryoporometry address the water content in hollow capsules, and the water pore size distribution, respectively. Multilayer material properties are relevant for different applications. As a novel concept, dielectric properties are monitored in a field effect transistor device. Ion mobility and redox processes in multilayers are revealed by the electrochemical properties. Mechanical properties of multilayers, studied by colloidal probe atomic force microscopy depend on the conformation of the polymers involved.
The formation of ultrathin polymer films by successive adsorption of polyelectrolytes of opposite... more The formation of ultrathin polymer films by successive adsorption of polyelectrolytes of opposite charge has been extensively studied from 1992 on. In all reported cases where organic polyelectrolytes have been used, the profuse intermixing which exists between subsequent layers results in virtually structureless films. However, we have recently discovered a possibility to obtain internally-structured films, by using polyelectrolytes of reduced
IFMBE Proceedings, 2014
Biomaterials aim to mimic in vivo extracellular matrices where cell interactions occur on the nan... more Biomaterials aim to mimic in vivo extracellular matrices where cell interactions occur on the nanoscale. Thus, incorporation of nanosized components is interesting in the preparation of bioactive surfaces. We present a technique using nanoimprint lithography to create chemical nanopatterns on silicon surfaces functionalized with bioactive motifs. Due to high throughput and versatility, a wide range of geometries and dimensions can be efficiently patterned. In our study, we prepared and characterized two types of bioactive nanodots (150 nm diameter with 350 nm spacing, and 80 nm diameter with 110 nm spacing) functionalized with cell adhesion-promoting RGD peptides. We examined mesenchymal stem cell adhesion and commitment on these modified material surfaces with respect to homogeneous RGD and non-functionalized surfaces. We report that bioactive nanostructures induce fibrillar adhesions on human mesenchymal stem cells with an impact on their behavior and dynamics specifically in terms of cell spreading, cell-material contact, and cell differentiation.
Polymer, 1999
New hydrophobically modified pullulans were synthesized in two ways: (i) neutral derivatives (HMP... more New hydrophobically modified pullulans were synthesized in two ways: (i) neutral derivatives (HMPFs) obtained by direct esterification of pullulan with a perfluoroalkyl carboxylic acid (C 8 F 17 CH 2 CH 2 COOH), and (ii) ionic derivatives (HMCMPs) obtained by amidation of carboxymethylpullulan with two perfluoroalkylamines (C 7 F 15 CH 2 NH 2 and C 8 F 17 CH 2 CH 2 NH 2). The molar hydrophobe contents ranged from 1.1 to 4.8% with respect to the anhydroglucose units. Associative properties in aqueous solutions were studied by rheological and sizeexclusion chromatography/light-scattering measurements. In dilute solution, the polymers form intermolecular aggregates with a more compact conformation than that of precursors. In semi-dilute solution, the ionic derivatives are more viscosifying than neutral because of their better solubility. This effect is significant as the alkylperfluorinated chain length increases.
Sensors and Actuators B: Chemical, 2012
Screen-printed carbon electrodes were modified with polyaniline by electrochemical oxidation to p... more Screen-printed carbon electrodes were modified with polyaniline by electrochemical oxidation to produce a potentiometric pH transducer. The resulting pH sensor exhibited a fast, reproducible and sensitive potentiometric response of approximately 59 mV per pH unit from pH 4 to 8. The pH sensor response was found to be stable in time for up to one month. Such potentiometric response was obtained for thick polyaniline films. Thinner polymer films exhibited less sensitive responses and were found to have a smaller lifetime. The sensitivity of polyaniline to pH variations was then used to design an enzymatic biosensor. For that purpose, urease was immobilized on a polyelectrolyte multilayer film (PEM), obtained by the alternate deposition of charged polysaccharides (layer-by-layer assembly, LbL), over the polyaniline film. Covalent grafting of the urease enzyme to the PEM film was also tested using carbodiimide coupling reaction. The potentiometric response of this assembly to pH variations was similar to the one of polyaniline films, and its response to urea, from 10 −4 to 10 −1 mol L −1 , exhibited a very high sensitivity combined to fast response, good lifetime and reproducibility. The number of polyelectrolyte layers composing the PEM film was also found to affect the response of the urea sensors.
Sequential Assembly of Nanocomposite Materials, 2012
ABSTRACT This chapter contains sections titled: * Introduction * Polyelectrolyte Films Incorporat... more ABSTRACT This chapter contains sections titled: * Introduction * Polyelectrolyte Films Incorporating Randomly Distributed Hydrophobic Nanodomains for Antimicrobial Applications * Multicompartmentalized Strati.ed Polyelectrolyte Films for Control of Energy Transfer * Conclusions and Perspectives * References
Electrochimica Acta, 2014
ABSTRACT Elaboration of original polymer materials using self-assembly and electrochemistry.•In s... more ABSTRACT Elaboration of original polymer materials using self-assembly and electrochemistry.•In situ monitoring of the growth of the polymer materials.•Development of urea electrochemical sensors using a home-made mini-potentiostat.
Multilayer Thin Films, 2002
Le pullulane est un polysaccharide de fermentation neutre caracterise par un squelette macromolec... more Le pullulane est un polysaccharide de fermentation neutre caracterise par un squelette macromoleculaire flexible. La presence de trois fonctions alcool par motif anhydroglucose a permis de le modifier chimiquement de facon a obtenir des composes associatifs porteurs de chainons perfluores. Des derives neutres ont d'abord ete synthetises par fixation d'un acide carboxylique C11 (< 4%) sur les fonctions hydroxyle. Cependant, ces echantillons ne presentent pas de proprietes viscosifiantes marquees par rapport au precurseur en raison d'une mauvaise solvatation des chaines macromoleculaires. Afin de renforcer l'hydrophilie du pullulane et permettre une bonne solubilisation des derives amphiphiles, des groupes carboxymethyle ont ete introduits sur le squelette polysaccharidique. Une etude RMN ( 1H et 13C) a montre que la substitution s'effectue principalement sur le carbone 3 et que la fonction hydroxyle situee sur le carbone 4 est la plus reactive vis-a-vis de la substitution. Les carboxymethylpullulanes (0,85 ≤ DS c o o ≤ 1) ont ensuite ete hydrophobises par greffage d'amines (2,5 a 7%) de longueur variable (C 8 a C 1 3) sur les fonctions acide carboxylique. Lors de cette synthese, une reaction secondaire entrainant la reticulation partielle du polymere apparait. En ajustant les conditions experimentales, des echantillons amphiphiles non reticules et partiellement reticules ont ete prepares. Les derives non reticules presentent des proprietes en solution classiques des polymeres associatifs du fait de l'etablissement de nombreuses associations hydrophobes intra et/ou intermoleculaires. Les proprietes viscosifiantes de ces composes sont fonction de parametres moleculaires (concentration en polymere, taux de greffage, longueur du greffon,) et de parametres exterieurs (force ionique, tensioactif,). Dans le cas des polymeres reticules, on obtient des microgels et les echantillons presentent un comportement typique d'une suspension.