Publications by authors named "Philippe Lavalle"

72 Publications

Prediction of coating thickness for polyelectrolyte multilayers via machine learning.

Sci Rep 2021 Sep 21;11(1):18702. Epub 2021 Sep 21.

SPARTHA Medical, 67100, Strasbourg, France.

Layer-by-layer (LbL) deposition method of polyelectrolytes is a versatile way of developing functional nanoscale coatings. Even though the mechanisms of LbL film development are well-established, currently there are no predictive models that can link film components with their final properties. The current health crisis has shown the importance of accelerated development of biomedical solutions such as antiviral coatings, and the implementation of machine learning methodologies for coating development can enable achieving this. In this work, using literature data and newly generated experimental results, we first analyzed the relative impact of 23 coating parameters on the coating thickness. Next, a predictive model has been developed using aforementioned parameters and molecular descriptors of polymers from the DeepChem library. Model performance was limited because of insufficient number of data points in the training set, due to the scarce availability of data in the literature. Despite this limitation, we demonstrate, for the first time, utilization of machine learning for prediction of LbL coating properties. It can decrease the time necessary to obtain functional coating with desired properties, as well as decrease experimental costs and enable the fast first response to crisis situations (such as pandemics) where coatings can positively contribute. Besides coating thickness, which was selected as an output value in this study, machine learning approach can be potentially used to predict functional properties of multilayer coatings, e.g. biocompatibility, cell adhesive, antibacterial, antiviral or anti-inflammatory properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-98170-xDOI Listing
September 2021

Insensitivity of dental pulp stem cells migration to substrate stiffness.

Biomaterials 2021 08 15;275:120969. Epub 2021 Jun 15.

Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France. Electronic address:

Dental pulp stem cells (DPSCs) are a promising cell source for regeneration of dental pulp. Migration is a key event but influence of the microenvironment rigidity (5 kPa at the center of dental pulp to 20 GPa for the dentin) is largely unknown. Mechanical signals are transmitted from the extracellular matrix to the cytoskeleton, to the nuclei, and to the chromatin, potentially regulating gene expression. To identify the microenvironmental influence on migration, we analyzed motility on PDMS substrates with stiffness increasing from 1.5 kPa up to 2.5 MPa. We found that migration speed slightly increases as substrate stiffness decreases in correlation with decreasing focal adhesion size. Motility is relatively insensitive to substrate stiffness, even on a bi-rigidity PDMS substrate where DPSCs migrate without preferential direction. Migration is independent of both myosin II activity and YAP translocation after myosin II inhibition. Additionally, inhibition of Arp2/3 complex leads to significant speed decrease for all rigidities, suggesting contribution of the lamellipodia in the migration. Interestingly, the chromatin architecture remains stable after a 7-days exposure on the PDMS substrates for all rigidity. To design scaffold mimicking dental pulp environment, similar DPSCs migration for all rigidity, leaves field open to choose this mechanical parameter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2021.120969DOI Listing
August 2021

Analytical strategy for studying the formation and stability of multilayered films containing gold nanoparticles.

Anal Bioanal Chem 2021 Feb 26;413(5):1473-1483. Epub 2021 Jan 26.

Université de Lorraine, CITHEFOR, 54000, Nancy, France.

The design of layer-by-layer (LbL) polyelectrolyte films including nanoparticles is a growing field of innovation in a wide range of biomedical applications. Gold nanoparticles (AuNPs) are very attractive for further biomolecule coupling to induce a pharmacological effect. Nanostructured LbL films coupled with such metallic species show properties that depend on the conditions of construction, i.e. the polymer nature and dissolution buffer. Tripartite LbL films (polycation, AuNP, and polyanion) were evaluated using two different polycationic polymers (poly(allylamine hydrochloride) (PAH), poly(ethylene imine) (PEI)) and various medium conditions (salts, i.e. phosphate, Tris or Tris-NaCl buffers, and concentration). AuNP incorporation and film stability were analysed by visible spectrophotometry, capillary zone electrophoresis, a quartz crystal microbalance, and high-performance liquid chromatography. The ideal compromise between AuNP loading and film stability was obtained using PAH prepared in Tris-NaCl buffer (0.01-0.15 M). This condition allowed the formation of a LbL film that was more stable than the film with PEI and provided an AuNP quantity that was 4.8 times greater than that of the PAH-PBS-built film. In conclusion, this work presents an analytical strategy for the characterization of nanostructured multilayer films and optimization of LbL films enriched with AuNPs to design biomedical device coatings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00216-020-03113-6DOI Listing
February 2021

Recent Advances in Antiinflammatory Material Design.

Adv Healthc Mater 2021 01 13;10(1):e2001373. Epub 2020 Oct 13.

Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121 Biomaterials and Bioengineering, 11 rue Humann, Strasbourg Cedex, 67085, France.

Implants and prostheses are widely used to replace damaged tissues or to treat various diseases. However, besides the risk of bacterial or fungal infection, an inflammatory response usually occurs. Here, recent progress in the field of anti-inflammatory biomaterials is described. Different materials and approaches are used to decrease the inflammatory response, including hydrogels, nanoparticles, implant surface coating by polymers, and a variety of systems for anti-inflammatory drug delivery. Complex multifunctional systems dealing with inflammation, microbial infection, bone regeneration, or angiogenesis are also described. New promising stimuli-responsive systems, such as pH- and temperature-responsive materials, are also being developed that would enable an "intelligent" antiinflammatory response when the inflammation occurs. Together, different approaches hold promise for creation of novel multifunctional smart materials allowing better implant integration and tissue regeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202001373DOI Listing
January 2021

New Smart Antimicrobial Hydrogels, Nanomaterials, and Coatings: Earlier Action, More Specific, Better Dosing?

Adv Healthc Mater 2021 01 12;10(1):e2001199. Epub 2020 Oct 12.

Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121 Biomaterials and Bioengineering, 11 rue Humann, Strasbourg Cedex, 67085, France.

To fight against antibiotic-resistant bacteria adhering and developing on medical devices, which is a growing problem worldwide, researchers are currently developing new "smart" materials and coatings. They consist in delivery of antimicrobial agents in an intelligent way, i.e., only when bacteria are present. This requires the use of new and sophisticated tools combining antimicrobial agents with lipids or polymers, synthetic and/or natural. In this review, three classes of innovative materials are described: hydrogels, nanomaterials, and thin films. Moreover, smart antibacterial materials can be classified into two groups depending on the origin of the stimulus used: those that respond to a nonbiological stimulus (light, temperature, electric and magnetic fields) and those that respond to a biological stimulus related to the presence of bacteria, such as changes in pH or bacterial enzyme secretion. The bacteria presence can induce a pH change that constitutes a first potential biological trigger allowing the system to become active. A second biological trigger signal consists in enzymes produced by bacteria themselves. A complete panel of recent studies will be given focusing on the design of such innovative smart materials that are sensitive to biological triggers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202001199DOI Listing
January 2021

Personalization of medical device interfaces: decreasing implant-related complications by modular coatings and immunoprofiling.

Future Sci OA 2020 Jul 30;6(8):FSO607. Epub 2020 Jul 30.

INSERM UMR1121 "Biomaterials & Bioengineering" 11 Rue Humann, 67000, Strasbourg, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2144/fsoa-2020-0074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491009PMC
July 2020

Polyarginine Decorated Polydopamine Nanoparticles With Antimicrobial Properties for Functionalization of Hydrogels.

Front Bioeng Biotechnol 2020 18;8:982. Epub 2020 Aug 18.

Institut National de la Santé et de la Recherche Médicale, INSERM UMR 1121 "Biomaterials and Bioengineering", Strasbourg, France.

Polydopamine (PDA) nanoparticles are versatile structures that can be stabilized with proteins. In this study, we have demonstrated the feasibility of developing PDA/polypeptides complexes in the shape of nanoparticles. The polypeptide can also render the nanoparticle functional. Herein, we have developed antimicrobial nanoparticles with a narrow size distribution by decorating the polydopamine particles with a chain-length controlled antimicrobial agent Polyarginine (PAR). The obtained particles were 3.9 ± 1.7 nm in diameter and were not cytotoxic at 1:20 dilution and above. PAR-decorated nanoparticles have exhibited a strong antimicrobial activity against , one of the most common pathogen involved in implant infections. The minimum inhibitory concentration is 5 times less than the cytotoxicity levels. Then, PAR-decorated nanoparticles have been incorporated into gelatin hydrogels used as a model of tissue engineering scaffolds. These nanoparticles have given hydrogels strong antimicrobial properties without affecting their stability and biocompatibility while improving their mechanical properties (modulus of increased storage). Decorated polydopamine nanoparticles can be a versatile tool for the functionalization of hydrogels in regenerative medicine applications by providing bioactive properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2020.00982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461895PMC
August 2020

Polyanionic Hydrogels as Reservoirs for Polycationic Antibiotic Substitutes Providing Prolonged Antibacterial Activity.

ACS Appl Mater Interfaces 2020 Apr 15;12(17):19258-19267. Epub 2020 Apr 15.

Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121 Biomaterials and Bioengineering, 11 rue Humann, 67085 Strasbourg Cedex, France.

Implantation of biomedical devices is often followed by bacterial infections that may seriously affect implant functionalities and lead to their failure. In the context of bacterial resistance to antibiotics, which is a growing problem worldwide, new strategies that are able to overcome these problems are needed. In this work, we introduce a new formulation of hyaluronic acid (HA)-based antimicrobial material: HA hydrogels loaded with polyarginine (PAR), a polycationic antibiotic substitute. The loading is possible through electrostatic interactions between negatively charged HA and positively charged PAR. Such hydrogels absorb high quantities of PAR, which are then gradually released from the hydrogel. This original system provides a long-lasting antibacterial effect on an in vitro model of repetitive infection, thus demonstrating a strong potential to fight multiple rounds of infections that are resistant to antibiotic treatment. In addition, HA-PAR hydrogels could be deposited onto/into medical devices such as wound dressings and mesh prostheses used in clinical applications. Finally, we performed first in vivo tests of hydrogel-coated mesh materials to verify their biocompatibility in a rat model, which show no difference between control HA hydrogel and PAR-loaded hydrogel in terms of inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b23140DOI Listing
April 2020

Design of surface ligands for blood compatible gold nanoparticles: Effect of charge and binding energy.

Int J Pharm 2020 Apr 19;580:119244. Epub 2020 Mar 19.

Université de Lorraine, CITHEFOR, Nancy, France. Electronic address:

Gold nanoparticle (AuNP) interaction with the blood compartment as a function of their charge and the binding energy of their surface ligand was explored. Citrate, polyallylamine and cysteamine stabilized AuNP along with dihydrolipoic acid and polyethylene glycol capped AuNP were synthesized and fully characterized. Their interactions with model proteins (human albumin and human fibrinogen) were studied. Complexes formed between AuNP and protein revealed several behaviors ranging from corona formation to aggregation. Protein fluorescence quenching as a function of temperature and AuNP concentration allowed the determination of the thermodynamic parameters describing these interactions. The hemolysis induced by AuNP was also probed: an increasing or a decreasing of hemolysis ratio induced by AuNP was observed as of function of protein corona formation. Taken together, our results drew up a composite sketch of an ideal surface ligand for blood compatible AuNP. This capping agent should be strongly bound to the gold core by one or more thiol groups and it must confer a negative charge to the particles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2020.119244DOI Listing
April 2020

Role of Trapped Air in the Attachment of on Superhydrophobic Silicone Elastomer Surfaces Textured by a Femtosecond Laser.

Langmuir 2020 02 3;36(5):1103-1112. Epub 2020 Feb 3.

Institut de Science des Matériaux de Mulhouse (IS2M) CNRS - UMR 7361, Université de Haute Alsace , 15 rue Jean Starcky BP2488 , 68057 Mulhouse , France.

Surface texturing is an easy way to control wettability as well as bacterial adhesion. Air trapped in the surface texture of an immersed sample was often proposed as the origin of the low adhesion of bacteria to surfaces showing superhydrophobic properties. In this work, we identified two sets of femtosecond laser processing parameters that led to extreme superhydrophobic textures on a silicone elastomer but showed opposite behavior against (S. aureus, ATCC 25923) over a short incubation times (6 h). The main difference from most of the previous studies was that the air trapping was not evaluated from the extrapolation of the results of the classical sessile drop technique but from the drop rebound and Wilhelmy plate method. Additionally, all wetting tests were performed with bacteria culture medium and at 37 °C in the case of the Wilhelmy plate method. Following this approach, we were able to study the formation of the liquid/silicone interface and the associated air trapping for immersed samples that is, by far, most representative of the cell culture conditions than those associated with the sessile drop technique. Finally, the conversion of these superhydrophobic coatings into superhydrophilic ones revealed that air trapping is not a necessary condition to avoid retention on one of these two textured surfaces at short incubation times.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.langmuir.9b03170DOI Listing
February 2020

Glycaemic control in diabetic rats treated with islet transplantation using plasma combined with hydroxypropylmethyl cellulose hydrogel.

Acta Biomater 2020 01 4;102:259-272. Epub 2019 Dec 4.

Centre Européen d'Etude du Diabète, DIATHEC EA 7294, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Boulevard René Leriche, 67000 Strasbourg, France. Electronic address:

Islet transplantation is one of the most efficient cell therapies used in clinics and could treat a large proportion of patients with diabetes. However, it is limited by the high requirement of pancreas necessary to provide the sufficient surviving islet mass in the hepatic tissue and restore normoglycaemia. Reduction in organ procurement requirements could be achieved by extrahepatic transplantation using a biomaterial that enhances islet survival and function. We report a plasma-supplemented hydroxypropyl methylcellulose (HPMC) hydrogel, engineered specifically using a newly developed technique for intra-omental islet infusion, known as hOMING (h-Omental Matrix Islet filliNG). The HPMC hydrogel delivered islets with better performance than that of the classical intrahepatic infusion. After the validation of the HPMC suitability for islets in vivo and in vitro, plasma supplementation modified the rheological properties of HPMC without affecting its applicability with hOMING. The biomaterial association was proven to be more efficient both in vitro and in vivo, with better islet viability and function than that of the current clinical intrahepatic delivery technique. Indeed, when the islet mass was decreased by 25% or 35%, glycaemia control was observed in the group of plasma-supplemented hydrogels, whereas no regulation was observed in the hepatic group. Plasma gelation, observed immediately post infusion, decreased anoïkis and promoted vascularisation. To conclude, the threshold mass for islet transplantation could be decreased using HPMC-Plasma combined with the hOMING technique. The simplicity of the hOMING technique and the already validated use of its components could facilitate its transfer to clinics. STATEMENT OF SIGNIFICANCE: One of the major limitations for the broad deployment of current cell therapy for brittle type 1 diabetes is the islets' destruction during the transplantation process. Retrieved from their natural environment, the islets are grafted into a foreign tissue, which triggers massive cell loss. It is mandatory to provide the islets with an 3D environment specifically designed for promoting isletimplantation to improve cell therapy outcomes. For this aim, we combined HPMC and plasma. HPMC provides suitable rheological properties to the plasma to be injectable and be maintained in the omentum. Afterwards, the plasma polymerises around the graft in vivo, thereby allowing their optimal integration into their transplantation site. As a result, the islet mass required to obtain glycaemic control was reduced by 35%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2019.11.047DOI Listing
January 2020

Multifunctional polymeric implant coatings based on gelatin, hyaluronic acid derivative and chain length-controlled poly(arginine).

Mater Sci Eng C Mater Biol Appl 2019 Nov 19;104:109898. Epub 2019 Jun 19.

Protip Medical, 8 Place de l'Hôpital, 67000 Strasbourg, France; INSERM UMR 1121, 11 rue Humann, 67085 Strasbourg, France. Electronic address:

Surface of the implantable devices is the root cause of several complications such as infections, implant loosening and chronic inflammation. There is an urgent need for multifunctional coatings that can address these shortcomings simultaneously in a manner similar to the structures of extracellular matrix. Herein, we developed a coating system composed of ECM components and a naturally derived polypeptide. The interactions between the coating components create an environment that enables incorporation of an antimicrobial/angiogenic polypeptide. The film composition is based gelatin and hyaluronic acid modified with aldehyde groups (HA-Ald) that can react with poly (arginine) (PAR) through transient interactions. Nanoplasmon measurements demonstrated a significantly higher loading of PAR in films containing HA-Ald with longer retention of PAR in the structure. The presence of PAR not only provides to the film surface antimicrobial (contact-killing) properties but also increased endothelial cell-cell contacts (PECAM) and VEGFA gene expression and secretion by human vascular endothelial cells. This multifunctional coating can be easily applied to surface of implants where it can enact on several problems simultaneously.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2019.109898DOI Listing
November 2019

On the Infectivity of Bacteriophages in Polyelectrolyte Multilayer Films: Inhibition or Preservation of Their Bacteriolytic Activity?

ACS Appl Mater Interfaces 2018 Oct 24;10(39):33545-33555. Epub 2018 Sep 24.

Université de Lorraine, Laboratoire de Chimie Physique et Microbiologie pour l'Environnement, LCPME, UMR 7564 , Villers-lès-Nancy F-54600 , France.

Antibiotic resistance in bacterial cells has motivated the scientific community to design new and efficient (bio)materials with targeted bacteriostatic and/or bactericide properties. In this work, a series of polyelectrolyte multilayer films differing in terms of polycation-polyanion combinations are constructed according to the layer-by-layer deposition method. Their capacities to host T4 and φx174 phage particles and maintain their infectivity and bacteriolytic activity are thoroughly examined. It is found that the macroscopic physicochemical properties of the films, which includes film thickness, swelling ratio, or mechanical stiffness (as derived by atomic force microscopy and spectroscopy measurements), do not predominantly control the selectivity of the films for hosting infective phages. Instead, it is evidenced that the intimate electrostatic interactions locally operational between the loaded phages and the polycationic and polyanionic PEM components may lead to phage activity reduction and preservation/enhancement, respectively. It is argued that the underlying mechanism involves the screening of the phage capsid receptors (operational in cell recognition/infection processes) because of the formation of either polymer-phage hetero-assemblies or polymer coating surrounding the bioactive phage surface.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.8b10424DOI Listing
October 2018

Chromatin de-condensation by switching substrate elasticity.

Sci Rep 2018 08 23;8(1):12655. Epub 2018 Aug 23.

Inserm UMR-S1121, 11 rue Humann, 67085, Strasbourg, France.

Mechanical properties of the cellular environment are known to influence cell fate. Chromatin de-condensation appears as an early event in cell reprogramming. Whereas the ratio of euchromatin versus heterochromatin can be increased chemically, we report herein for the first time that the ratio can also be increased by purely changing the mechanical properties of the microenvironment by successive 24 h-contact of the cells on a soft substrate alternated with relocation and growth for 7 days on a hard substrate. An initial contact with soft substrate caused massive SW480 cancer cell death by necrosis, whereas approximately 7% of the cells did survived exhibiting a high level of condensed chromatin (21% heterochromatin). However, four consecutive hard/soft cycles elicited a strong chromatin de-condensation (6% heterochromatin) correlating with an increase of cellular survival (approximately 90%). Furthermore, cell survival appeared to be reversible, indicative of an adaptive process rather than an irreversible gene mutation(s). This adaptation process is associated with modifications in gene expression patterns. A completely new approach for chromatin de-condensation, based only on mechanical properties of the microenvironment, without any drug mediation is presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-31023-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107547PMC
August 2018

β-Cyclodextrin-Functionalized Chitosan/Alginate Compact Polyelectrolyte Complexes (CoPECs) as Functional Biomaterials with Anti-Inflammatory Properties.

ACS Appl Mater Interfaces 2018 Sep 24;10(35):29347-29356. Epub 2018 Aug 24.

Faculté de Pharmacie , Université de Strasbourg, CNRS, Laboratoire de Conception et Application de Molécules Bioactives UMR 7199 , 74 route du Rhin , 67401 Illkirch Cedex, France.

Nowadays, the need for therapeutic biomaterials displaying anti-inflammatory properties to fight against inflammation-related diseases is continuously increasing. Compact polyelectrolyte complexes (CoPECs) represent a new class of materials obtained by ultracentrifugation of a polyanion/polycation complex suspension in the presence of salt. Here, a noncytotoxic β-cyclodextrin-functionalized chitosan/alginate CoPEC was formulated, characterized, and described as a promising drug carrier displaying an intrinsic anti-inflammatory property. This new material was successfully formed, and due to the presence of cyclodextrins, it was able to trap and release hydrophobic drugs such as piroxicam used as a model drug. The intrinsic anti-inflammatory activity of this CoPEC was analyzed in vitro using murine macrophages in the presence of lipopolysaccharide (LPS) endotoxin. In this model, it was shown that CoPEC inhibited LPS-induced TNF-α and NO release and moderated the differentiation of LPS-activated macrophages. Over time, this kind of bioactive biomaterial could constitute a new family of delivery systems and expand the list of therapeutic tools available to target inflammatory chronic diseases such as arthritis or Crohn's disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.8b09733DOI Listing
September 2018

D-Cateslytin, a new antimicrobial peptide with therapeutic potential.

Sci Rep 2017 11 9;7(1):15199. Epub 2017 Nov 9.

Université de Strasbourg, Faculté de Chirurgie Dentaire, 3 rue Sainte Elisabeth, 67000, Strasbourg, France.

The rise of antimicrobial resistant microorganisms constitutes an increasingly serious threat to global public health. As a consequence, the efficacy of conventional antimicrobials is rapidly declining, threatening the ability of healthcare professionals to cure common infections. Over the last two decades host defense peptides have been identified as an attractive source of new antimicrobials. In the present study, we characterized the antibacterial and mechanistic properties of D-Cateslytin (D-Ctl), a new epipeptide derived from L-Cateslytin, where all L-amino acids were replaced by D-amino acids. We demonstrated that D-Ctl emerges as a potent, safe and robust peptide antimicrobial with undetectable susceptibility to resistance. Using Escherichia coli as a model, we reveal that D-Ctl targets the bacterial cell wall leading to the permeabilization of the membrane and the death of the bacteria. Overall, D-Ctl offers many assets that make it an attractive candidate for the biopharmaceutical development of new antimicrobials either as a single therapy or as a combination therapy as D-Ctl also has the remarkable property to potentiate several antimicrobials of reference such as cefotaxime, amoxicillin and methicillin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-15436-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680178PMC
November 2017

Localized Supramolecular Peptide Self-Assembly Directed by Enzyme-Induced Proton Gradients.

Angew Chem Int Ed Engl 2017 12 16;56(50):15984-15988. Epub 2017 Nov 16.

Université de Strasbourg, CNRS, Institut Charles Sadron (UPR22), 23 rue du Loess, BP 84047, 67034, Strasbourg Cedex 2, France.

Electrodes are ideal substrates for surface localized self-assembly processes. Spatiotemporal control over such processes is generally directed through the release of ions generated by redox reactions occurring specifically at the electrode. The so-used gradients of ions proved their effectiveness over the last decade but are in essence limited to material-based electrodes, considerably reducing the scope of applications. Herein is described a strategy to enzymatically generate proton gradients from non-conductive surfaces. In the presence of oxygen, immobilization of glucose oxidase (GOx) on a multilayer film provides a flow of protons through enzymatic oxidation of glucose by GOx. The confined acidic environment located at the solid-liquid interface allows the self-assembly of Fmoc-AA-OH (Fmoc=fluorenylmethyloxycarbonyl and A=alanine) dipeptides into β-sheet nanofibers exclusively from and near the surface. In the absence of oxygen, a multilayer nanoreactor containing GOx and horseradish peroxidase (HRP) similarly induces Fmoc-AA-OH self-assembly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201709029DOI Listing
December 2017

Establishing contact between cell-laden hydrogels and metallic implants with a biomimetic adhesive for cell therapy supported implants.

Biomed Mater 2017 12 15;13(1):015015. Epub 2017 Dec 15.

ProtipMedical, Strasbourg, France. INSERM, UMR-S 1121, 'Biomatériaux et Bioingénierie', 11 rue Humann, F-67085 Strasbourg Cedex, France.

For in-dwelling implants, controlling the biological interface is a crucial parameter to promote tissue integration and prevent implant failure. For this purpose, one possibility is to facilitate the establishment of the interface with cell-laden hydrogels fixed to the implant. However, for proper functioning, the stability of the hydrogel on the implant should be ensured. Modification of implant surfaces with an adhesive represents a promising strategy to promote the adhesion of a cell-laden hydrogel on an implant. Herein, we developed a peptidic adhesive based on mussel foot protein (L-DOPA-L-lysine)-L-DOPA that can be applied directly on the surface of an implant. At physiological pH, unoxidized (L-DOPA-L-lysine)-L-DOPA was supposed to strongly adhere to metallic surfaces but it only formed a very thin coating (less than 1 nm). Once oxidized at physiological pH, (L-DOPA-L-lysine)-L-DOPA forms an adhesive coating about 20 nm thick. In oxidized conditions, L-lysine can adhere to metallic substrates via electrostatic interaction. Oxidized L-DOPA allows the formation of a coating through self-polymerization and can react with amines so that this adhesive can be used to fix extra-cellular matrix based materials on implant surfaces through the reaction of quinones with amino groups. Hence, a stable interface between a soft gelatin hydrogel and metallic surfaces was achieved and the strength of adhesion was investigated. We have shown that the adhesive is non-cytotoxic to encapsulated cells and enabled the adhesion of gelatin soft hydrogels for 21 days on metallic substrates in liquid conditions. The adhesion properties of this anchoring peptide was quantified by a 180° peeling test with a more than 60% increase in peel strength in the presence of the adhesive. We demonstrated that by using a biomimetic adhesive, for the application of cell-laden hydrogels to metallic implant surfaces, the hydrogel/implant interface can be ensured without relying on the properties of the deposited biomaterials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1748-605X/aa895bDOI Listing
December 2017

Auxiliary Biomembranes as a Directional Delivery System To Control Biological Events in Cell-Laden Tissue-Engineering Scaffolds.

ACS Omega 2017 Mar 15;2(3):918-929. Epub 2017 Mar 15.

INSERM UMR 1121, 11 rue Humann, 67085 Strasbourg, France.

Delivery of growth factors is an indispensable part of tissue engineering. Here, we describe a detachable membrane-based release system composed of extracellular matrix components that can be attached to hydrogels to achieve directional release of bioactive molecules. This way, the release of cytokines/growth factors can be started at a desired point of tissue maturation or directly in vivo. As a model, we develop thin films of an interpenetrating network of double-cross-linked gelatin and hyaluronic acid derivatives. The use of the auxiliary release system with vascular endothelial growth factor results in extensive sprouting by encapsulated vascular endothelial cells. The presence of the release system with interleukin-4 results in clustering of encapsulated macrophages with a significant decrease in M1 macrophages (proinflammatory). This system can be used in conjunction with three-dimensional structures as an auxiliary system to control artificial tissue maturation and growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.6b00502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044576PMC
March 2017

The tumor suppressor CDX2 opposes pro-metastatic biomechanical modifications of colon cancer cells through organization of the actin cytoskeleton.

Cancer Lett 2017 02 2;386:57-64. Epub 2016 Nov 2.

INSERM UMR_S1113, Strasbourg, F-67200, France; FMTS, Université de Strasbourg, Strasbourg, F-67000, France. Electronic address:

The vast majority of cancer deaths are caused by the formation of metastases rather than the primary tumor itself. Despite this clinical importance, the molecular and cellular events that support the dissemination of cancer cells are not yet fully unraveled. We have previously shown that CDX2, a homeotic transcription factor essential for gut development, acts as a colon-specific tumor suppressor and opposes metastasis. Here, using a combination of biochemical, biophysical, and immunofluorescence techniques, we further investigated the mechanisms promoted by CDX2 that might antagonize tumor cell dissemination. We found that CDX2 expression regulates the transcription of RHO GEFs, thereby activating RHO signaling cascades that lead to reorganization of the actin cytoskeleton and enhanced adherent junctions. Accordingly, we observed by atomic force microscopy (AFM) that colon cancer cells expressing CDX2 are less deformable, a feature that has been shown to correlate with poor metastatic potential. Thus, this study illustrates how the loss of expression of a transcription factor during colon cancer progression modifies the biomechanical characteristics of tumor cells and hence facilitates invasion and metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2016.10.040DOI Listing
February 2017

Hyaluronic Acid and Its Derivatives in Coating and Delivery Systems: Applications in Tissue Engineering, Regenerative Medicine and Immunomodulation.

Adv Healthc Mater 2016 11 6;5(22):2841-2855. Epub 2016 Oct 6.

Inserm UMR 1121, 11 rue Humann, 67085, Strasbourg, France.

As an Extracellular Matrix (ECM) component, Hyaluronic acid (HA) plays a multi-faceted role in cell migration, proliferation and differentiation at micro level and system level events such as tissue water homeostasis. Among its biological functions, it is known to interact with cytokines and contribute to their retention in ECM microenvironment. In addition to its biological functions, it has advantageous physical properties which result in the industrial endeavors in the synthesis and extraction of HA for variety of applications ranging from medical to cosmetic. Recently, HA and its derivatives have been the focus of active research for applications in biomedical device coatings, drug delivery systems and in the form of scaffolds or cell-laden hydrogels for tissue engineering. A specific reason for the increase in use of HA based structures is their immunomodulatory and regeneration inducing capacities. In this context, this article reviews recent literature on modulation of the implantable biomaterial microenvironment by systems based on HA and its derivatives, particularly hydrogels and microscale coatings that are able to deliver cytokines in order to reduce the adverse immune reactions and promote tissue healing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.201600316DOI Listing
November 2016

Soft-Mechanochemistry: Mechanochemistry Inspired by Nature.

Langmuir 2016 07 19;32(29):7265-76. Epub 2016 Jul 19.

Institut Charles Sadron, Centre National de la Recherche Scientifique, Université de Strasbourg , 23 rue du Loess, 67034 Strasbourg Cedex 2, France.

Cells and bacteria use mechanotransduction processes to transform a mechanical force into a chemical/biochemical response. The area of chemistry where chemical reactions are induced by mechanical forces is called mechanochemistry. Over the last few years, chemists developed force-induced reactions affecting covalent bonds in molecules under tension which requires high energy input and/or high intensity forces. In contrast, in nature, mechanotransduction processes take place with forces of much weaker intensity and much less demanding energy. They are mainly based on protein conformational changes or changes in supramacromolecular architectures. Mechanochemistry based on such low-energy-demanding processes and which does not affect chemical bonds can be called soft-mechanochemistry. In this feature article, we first discuss some examples of soft-mechanochemistry processes encountered in nature, in particular, cryptic sites, allowing us to define more precisely the concepts underlying soft-mechanochemistry. A series of examples, developed over the past few years, of chemomechanoresponsive systems based on soft-mechanochemistry principles are given. We describe, in particular, cryptic site surfaces, enzymatically active films whose activity can be modulated by stretching and films where stretching induces changes in their fluorescence properties. Finally, we give our view of the future of soft-mechanochemistry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.langmuir.6b01768DOI Listing
July 2016

Immunomodulation with Self-Crosslinked Polyelectrolyte Multilayer-Based Coatings.

Biomacromolecules 2016 06 24;17(6):2189-98. Epub 2016 May 24.

INSERM UMR 1121 , 11 rue Humann, 67085 Strasbourg, France.

This study aims to design an optimal polyelectrolyte multilayer film of poly-l-lysine (PLL) and hyaluronic acid (HA) as an anti-inflammatory cytokine release system in order to decrease the implant failure due to any immune reactions. The chemical modification of the HA with aldehyde moieties allows self-cross-linking of the film and an improvement in the mechanical properties of the film. The cross-linking of the film and the release of immunomodulatory cytokine (IL-4) stimulate the differentiation of primary human monocytes seeded on the films into pro-healing macrophages phenotype. This induces the production of anti-inflammatory cytokines (IL1-RA and CCL18) and the decrease of pro-inflammatory cytokines secreted (IL-12, TNF-α, and IL-1β). Moreover, we demonstrate that cross-linking PLL/HA film using HA-aldehyde is already effective by itself to limit inflammatory processes. Finally, this functionalized self-cross-linked PLL/HA-aldehyde films constitutes an innovative and efficient candidate for immunomodulation of any kind of implants of various architecture and properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.biomac.6b00429DOI Listing
June 2016

Cell-laden hydrogel/titanium microhybrids: Site-specific cell delivery to metallic implants for improved integration.

Acta Biomater 2016 Mar 21;33:301-10. Epub 2016 Jan 21.

Protip Medical, 8 Place de l'Hopital, 67000 Strasbourg, France. Electronic address:

Unlabelled: Porous titanium implants are widely used in dental, orthopaedic and otorhinolaryngology fields to improve implant integration to host tissue. A possible step further to improve the integration with the host is the incorporation of autologous cells in porous titanium structures via cell-laden hydrogels. Fast gelling hydrogels have advantageous properties for in situ applications such as localisation of specific cells and growth factors at a target area without dispersion. The ability to control the cell types in different regions of an implant is important in applications where the target tissue (i) has structural heterogeneity (multiple cell types with a defined spatial configuration with respect to each other); (ii) has physical property gradients essential for its function (such as in the case of osteochondral tissue transition). Due to their near immediate gelation, such gels can also be used for site-specific modification of porous titanium structures, particularly for implants which would face different tissues at different locations. Herein, we describe a step by step design of a model system: the model cell-laden gel-containing porous titanium implants in the form of titanium microbead/hydrogel (maleimide-dextran or maleimide-PVA based) microhybrids. These systems enable the determination of the effect of titanium presence on gel properties and encapsulated cell behaviour as a miniaturized version of full-scale implants, providing a system compatible with conventional analysis methods. We used a fibroblast/vascular endothelial cell co-cultures as our model system and by utilising single microbeads we have quantified the effect of gel microenvironment (degradability, presence of RGD peptides within gel formulation) on cell behaviour and the effect of the titanium presence on cell behaviour and gel formation. Titanium presence slightly changed gel properties without hindering gel formation or affecting cell viability. Cells showed a preference to move towards the titanium beads and fibroblast proliferation was significantly higher in hybrids compared to gel only controls. The MMP (Matrix Metalloproteinase)-sensitive hydrogels induced sprouting by cells in co-culture configuration which was quantified by fluorescence microscopy, confocal microscopy and qRT-PCR (Quantitative Reverse transcription polymerase chain reaction). When the microhybrid up-scaled to 3D thick structures, cellular localisation in specific areas of the 3D titanium structures was achieved, without decreasing overall cell proliferation compared to titanium only scaffolds. Microhybrids of titanium and hydrogels are useful models for deciding the necessary modifications of metallic implants and they can be used as a modelling system for the study of tissue/titanium implant interactions.

Statement Of Significance: This article demonstrates a method to apply cell-laden hydrogels to porous titanium implants and a model of titanium/hydrogel interaction at micro-level using titanium microbeads. The feasibility of site-specific modification of titanium implants with cell-laden microgels has been demonstrated. Use of titanium microbeads in combination with hydrogels with conventional analysis techniques as described in the article can facilitate the characterisation of surface modification of titanium in a relevant model system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2016.01.023DOI Listing
March 2016

Antibacterial Peptide-Based Gel for Prevention of Medical Implanted-Device Infection.

PLoS One 2015 14;10(12):e0145143. Epub 2015 Dec 14.

Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche-S 1121, Biomatériaux et Bioingénierie, Strasbourg, France.

Implanted medical devices are prone to infection. Designing new strategies to reduce infection and implant rejection are an important challenge for modern medicine. To this end, in the last few years many hydrogels have been designed as matrices for antimicrobial molecules destined to fight frequent infection found in moist environments like the oral cavity. In this study, two types of original hydrogels containing the antimicrobial peptide Cateslytin have been designed. The first hydrogel is based on alginate modified with catechol moieties (AC gel). The choice of these catechol functional groups which derive from mussel's catechol originates from their strong adhesion properties on various surfaces. The second type of gel we tested is a mixture of alginate catechol and thiol-terminated Pluronic (AC/PlubisSH), a polymer derived from Pluronic, a well-known biocompatible polymer. This PlubisSH polymer has been chosen for its capacity to enhance the cohesion of the composition. These two gels offer new clinical uses, as they can be injected and jellify in a few minutes. Moreover, we show these gels strongly adhere to implant surfaces and gingiva. Once gelled, they demonstrate a high level of rheological properties and stability. In particular, the dissipative energy of the (AC/PlubisSH) gel detachment reaches a high value on gingiva (10 J.m-2) and on titanium alloys (4 J.m-2), conferring a strong mechanical barrier. Moreover, the Cateslytin peptide in hydrogels exhibited potent antimicrobial activities against P. gingivalis, where a strong inhibition of bacterial metabolic activity and viability was observed, indicating reduced virulence. Gel biocompatibility tests indicate no signs of toxicity. In conclusion, these new hydrogels could be ideal candidates in the prevention and/or management of periimplant diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145143PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682826PMC
July 2016

Stretch-Induced Helical Conformations in Poly(l-lysine)/Hyaluronic Acid Multilayers.

ACS Appl Mater Interfaces 2016 06 8;8(24):14958-65. Epub 2015 Dec 8.

Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121 , 11 rue Humann, 67085 Strasbourg Cedex, France.

We investigate the effect of stretching on the secondary structure of cross-linked poly(l-lysine)/hyaluronic acid (PLL/HA) multilayers. We show that stretching these films induces changes in the secondary structure of PLL chains. Our results suggest that not only α- but also 310-helices might form in the film under stretching. Such 310-helices have never been observed for PLL so far. These changes of the secondary structure of PLL are reversible, i.e., when returning to the nonstretched state one recovers the initial film structure. Using molecular dynamics simulations of chains composed of 20 l-lysine residues (PLL20), we find that these chains never adopt a helical conformation in water. In contrast, when the end-to-end distance of the chains is restrained to values smaller than the mean end-to-end distance of free chains, a distance domain rarely explored by the free chains, helical conformations become accessible. Moreover, the formation of not only α- but also 310-helices is predicted by the simulations. These results suggest that the change of the end-to-end distance of PLL chains in the stretched film is at the origin of the helix formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.5b08302DOI Listing
June 2016

Polyelectrolyte Multilayers: A Versatile Tool for Preparing Antimicrobial Coatings.

Langmuir 2015 Dec 18;31(47):12856-72. Epub 2015 Nov 18.

Centre National de la Recherche Scientifique, Institut Charles Sadron, UPR 22 , 23 rue du Loess, 67034 Strasbourg, France.

The prevention of pathogen colonization of medical implants represents a major medical and financial issue. The development of antimicrobial coatings aimed at protecting against such infections has thus become a major field of scientific and technological research. Three main strategies are developed to design such coatings: (i) the prevention of microorganisms adhesion and the killing of microorganisms (ii) by contact and (iii) by the release of active compounds in the vicinity of the implant. Polyelectrolyte multilayer (PEM) technology alone covers the entire widespread spectrum of functionalization possibilities. PEMs are obtained through the alternating deposition of polyanions and polycations on a substrate, and the great advantages of PEMs are that (i) they can be applied to almost any type of substrate whatever its shape and composition; (ii) various chemical, physicochemical, and mechanical properties of the coatings can be obtained; and (iii) active compounds can be embedded and released in a controlled manner. In this article we will give an overview of the field of PEMs applied to the design of antimicrobial coatings, illustrating the large versatility of the PEM technology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.langmuir.5b02768DOI Listing
December 2015

Harnessing the multifunctionality in nature: a bioactive agent release system with self-antimicrobial and immunomodulatory properties.

Adv Healthc Mater 2015 Sep;4(13):2026-36

Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, 11 rue Humann, 67085, Strasbourg, France.

Major problems with biomedical devices in particular implants located in nonsterile environments concern: (i) excessive immune response to the implant, (ii) development of bacterial biofilms, and (iii) yeast and fungi infections. An original multifunctional coating that addresses all these issues concomitantly is developed. A new exponentially growing polyelectrolyte multilayer film based on polyarginine (PAR) and hyaluronic acid (HA) is designed. The films have a strong inhibitory effect on the production of inflammatory cytokines released by human primary macrophage subpopulations. This could reduce potential chronic inflammatory reaction following implantation. Next, it is shown that PAR, due to its positive charges, has an antimicrobial activity in film format against Staphylococcus aureus for 24 h. In order to have a long-term antimicrobial activity, a precursor nanoscale silver coating is deposited on the surface before adding the PAR/HA films. Moreover, the PAR/HA films can be easily further functionalized by embedding antimicrobial peptides, like catestatin (CAT), a natural host defense peptide. This PAR/HA+CAT film proves to be effective as an antimicrobial coating against yeast and fungi and its cytocompatibility is also assessed. Finally, this all-in-one system constitutes an original strategy to limit inflammation and prevents bacteria, yeast, and fungi infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.201500546DOI Listing
September 2015

Priming cells for their final destination: microenvironment controlled cell culture by a modular ECM-mimicking feeder film.

Biomater Sci 2015 Sep;3(9):1302-11

Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, Biomaterials and Bioengineering, 11 rue Humann, 67085 Strasbourg Cedex, France.

Mammalian cell culture is the starting point in many research studies focusing on biomedical applications. However, researchers have little control over the standardized cell microenvironment parameters. Here a modular ECM-mimicking surface coating for cell culture environment is designed. This substrate is a new and versatile thin film obtained by spin-coating of concentrated gelatin crosslinked by transglutaminase. It can be modified with respect to the biochemical and biophysical needs of the final cell destination, i.e. it delivers loaded multi-growth factors and serum components and allows for cell culture in a serum-free culture medium. Also, a well-known cell behavior modulator, the substrate stiffness, is controlled exogenously by addition of nanoparticles. In addition to growth factors, antimicrobial agents such as natural peptides are added to the substrate for limiting the repeated addition of antimicrobial agents to the culture medium and to prevent the increase of resistant bacterial strains in the culture environment. Finally, this substrate contains simultaneously ECM components, growth factors, stiffening elements and antimicrobial agents. It provides a favorable microenvironment and sterile conditions. It is a free-of-maintenance system, as cells will grow without addition of serum or antimicrobial cocktails. This low cost and easy-to-use substrate could emerge as a new standard for cell culture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c5bm00172bDOI Listing
September 2015

Bioactive Seed Layer for Surface-Confined Self-Assembly of Peptides.

Angew Chem Int Ed Engl 2015 Aug 15;54(35):10198-201. Epub 2015 Jul 15.

Institut Charles Sadron, CNRS-UPR 22, 23 rue du Loess, 67034 Strasbourg Cedex (France).

The design and control of molecular systems that self-assemble spontaneously and exclusively at or near an interface represents a real scientific challenge. We present here a new concept, an active seed layer that allows to overcome this challenge. It is based on enzyme-assisted self-assembly. An enzyme, alkaline phosphatase, which transforms an original peptide, Fmoc-FFY(PO4 (2-) ), into an efficient gelation agent by dephosphorylation, is embedded in a polyelectrolyte multilayer and constitutes the "reaction motor". A seed layer composed of a polyelectrolyte covalently modified by anchoring hydrogelator peptides constitutes the top of the multilayer. This layer is the nucleation site for the Fmoc-FFY peptide self-assembly. When such a film is brought in contact with a Fmoc-FFY(PO4 (2-) ) solution, a nanofiber network starts to form almost instantaneously which extents up to several micrometers into the solution after several hours. We demonstrate that the active seed layer allows convenient control over the self-assembly kinetics and the geometric features of the fiber network simply by changing its peptide density.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201504761DOI Listing
August 2015
-->