34 research outputs found
Copolymère hydrophobe visible en IRM
The invention relates to a hydrophobic thermoplastic copolymer which is in particular of use for manufacturing and/or coating medical devices, in particular implantable medical devices, characterized in that it is obtained by copolymerization, and in that it comprises at least one first monomer unit and at least one second monomer unit onto which is grafted a paramagnetic-ion-chelating ligand which can complex with such a paramagnetic ion or a paramagnetic-ion-chelating ligand which is complexed with such a paramagnetic ion, wherein the second monomer unit is grafted in sufficient amount for the copolymer to be visible in magnetic resonance imaging when it is complexed with said paramagnetic ion. The invention also relates to a method for obtaining said hydrophobic thermoplastic copolymer
MRI-visible polymer based on poly(methyl methacrylate) for imaging applications
Macromolecular contrast agents are very attractive to afford efficient magnetic resonance imaging (MRI) visualization of implantable medical devices. In this work, we report on the grafting of a Gd-based DTPA contrast agent onto a poly(methyl methacrylate) derivative backbone by combining free radical polymerization and copper-catalyzed azide-alkyne cycloaddition (CuAAC). Using free radical polymerization, poly(methyl methacrylate-co-propargyl methacrylate) copolymers were prepared with a control of the ratio in propargyl methacrylate monomer units. The synthesis of a new azido monofunctionalized DTPA ligand was also reported and characterized by 1H NMR and mass spectroscopy. After complexation with gadolinium, this ligand has been grafted on the polymer backbone by click chemistry reaction. The obtained macromolecular contrast agent was then coated on a polypropylene mesh using the airbrushing technique and the mesh was assessed for MRI visualization at 7 teslas. The polymeric contrast agent was also tested for cytocompatibility and stability to assess its suitability for biomedical applications
Toward potent antibiofilm degradable medical devices: A generic method for the antibacterial surface modification of polylactide
The effects of biomaterials on their environment must be carefully modulated in most biomedical applications. Among other approaches, this modulation can be obtained through the modification of the biomaterial surface. This paper proposes a simple and versatile strategy to produce non-leaching antibacterial polylactide (PLA) surfaces without any degradation of the polyester chains. The method is based on a one-pot procedure that provides a clickable PLA surface via anionic activation which is then functionalized with an antibacterial quaternized poly(2-(dimethylamino)ethyl methacrylate) (QPDMAEMA) by covalent immobilization on the surface. The anti-adherence and antibiofilm activities of modified PLA surfaces are assessed for different QPDMAEMA molecular weights and different quaternization agents. Antibacterial PLA surfaces are shown to be very active against Gram-negative and Gram-positive strains, with adherence reduction factors superior to 99.999% and a marked reduction in biofilm on the most potent surfaces. In addition to this substantial antibacterial activity, the proposed PLA surfaces are also cytocompatible, as demonstrated through the proliferation of L929 fibroblasts
TOWARD POTENT ANTIBIOFILM DEGRADABLE MEDICAL DEVICES: GENERIC METHODOLOGIES FOR THE SURFACE MODIfiCATION OF POLYLACTIDE
Surface post-modification of polylactide is combined
to CuAAc click chemistry or thiol-yne click
photochemistry to yield antibiofilm surfaces.
INTRODUCTION
As a direct result of the life expectancy increase,
implants are increasingly used for the restoration of
human anatomy and functions. However, this is
accompanied with the development of biomaterialassociated
septic failures1. To limit these risks, the
modulation of the antibacterial surface properties of
prosthetic materials appears therefore as a convenient
and efficient strategy. In this frame, postpolymerization
modification approaches, especially
click chemistry, have attracted much attention in the last
decade2. In this communication, we wish to report on
the recent post-modification strategies developed by our
group to yield polylactide antibacterial surfaces.
EXPERIMENTAL METHODS
PLA surfaces were activated via anionic chemical
modification to anchor alkyne moieties, according to a
reaction previously described by our group3. This
clickable PLA intermediate was then engaged in two
distinct strategies. In a first approach, well-controlled
quaternized PDMAEMA chains (5-10 kDa) with an
azide chain-end were synthesized and covalently
grafted to the PLA clickable surfaces by CuAAc 1,3-
dipolar cycloaddition. In a second approach, cationic
derivatives of α,β-poly(N-2-hydroxyethyl)-aspartamide
(PHEA) were functionalized with lipoic acid (LA).
Photoactivated thiol-yne reaction was done under UV
by reacting PHEA-LA at the surface of the clickable
PLA in the presence of TCEP. All polymers have been
characterized by NMR and SEC analyses. After careful
washes, surfaces were analysed by AFM and XPS.
Antibacterial activity was tested against four bacterial
strains. Adherence of bacteria and biofilm formation
were tested. Cytocompatibility was evaluated with L929
fibroblasts. All data are expressed as means ± SD and
correspond to measurements in triplicate.
RESULTS AND DISCUSSION
Thanks to the use of optimized and mild activation
conditions, alkyne functionalized PLA surfaces were
obtained without degradation as already reported
elsewehere6. CuAAc cycloaddition of QPDMAEMA
chains was evaluated by XPS and showed an overall
10% coverage of the PLA surface by QPDMAEMA. No
residual copper was detected. Activity was strong
against all bacterial strains, including E. Coli and S.
Aureus with a clear dependence of the antibacterial
activity over QPDMAEMA molecular weight and
alkylating agent (Figure 1). Best results were obtained
for Mn = 10 000 g/mol and heptyl group with adherence
reduction factors > 99.999% (ASTM E 2149–01) and
strong bactericidal activity.
Fig. 1. Antibacterial activity of antibacterial PLA surface (red bars)
against four bacterial strains. PLA plates are shown as control (brown
bars).4
With short reaction times and no metals used, UV
photoactivated thiol-yne grafting of PHEA-LA was
studied as a green alternative to CuAAc.
Advantageously, the heterogeneous surface reaction
took place in aqueous media. Various solvent mixtures
were tested and best results were obtained in slightly
acidic water/ethanol (1:1) medium, in the presence of
TCEP and with a 15 min irradiation time per PLA plate
side. Under these conditions, XPS confirmed the
covalent grafting of the cationic PHEA-LA derivative.
As for CuAAc, antibacterial and antibiofilm activities
were tested with again reduction factors > 99.999% and
up to 80% biofilm decrease for all four bacterial strains.
Interestingly, whatever the methodology used all
surfaces showed a good cytocompatibility towards
L929 fibroblasts cells with respect to TCPS control.
CONCLUSION
Antibacterial PLA surface modification was obtained in
an efficient two steps approach by combining anionic
and click chemistries. For the first time green thiol-yne
strategy was applied to PLA surfaces, which paves the
way to further developments in the biomedical field.
REFERENCES
1. Campoccia D. et al. Biomaterials 34:8018-8029, 2013
2. Theato P. & Klok H-A. Eds. Wiley-CH, 2013
3. El Habnouni S. et al. Adv. Funct. Mater. 21:3321-3330, 2011
4. El Habnouni S. et al. Acta Biomater. 9 :7709-7718, 2013
ACKNOWLEDGMENTS
Authors thank the French MESR for PhD fundings