56 research outputs found
Electrospinning of drug loaded poly(ε-caprolactone) nanofibers: In vivo evaluation of novel degradable small-sized vascular grafts
No full textElectrospinning of Drug Loaded Poly(ε-Caprolactone) Nanofibers: Towards Novel Degradable Small-Sized Vascular Grafts
No full textMODIFICATION OF HYDROPHOBIC SURFACE WITH POLYASPARTAMIDE-BASED POLYCATIONS FOR BIOMEDICAL APPLICATION
No full textA convenient way for the achievement of polymer-based solid materials for specific biomedical applications is grafting the appropriate macromolecules onto the surfaces in order to confer them specific properties. To date many approaches have been used to covalently modify polymeric surfaces, and among them chemoselective coupling reactions, usually referred as “click” reactions, gained much attention thanks to simple procedure with high reaction rate under mild reaction conditions (at normal temperature and pressure) [1]. In particular, radical-initiated thiol-yne “photo-click” chemistry has been demonstrated as an effective way to functionalize efficiently surfaces. This method gives also the possibility to avoid the presence of residual metal impurities and to increase the density of surface functionalization, thanks to the possibility to yield bis-addition products on triple bonds [2].
In this frame, copper catalysed “click” chemistry was recently used to confer antibacterial and antibiofilm properties to propargylated PLA surfaces by immobilization of polyquaternary ammoniums.[3] Here, this approach was enlarged to thiol-yne “photo-click” chemistry that was used to link a polyaspartamide copolymer, bearing positive permanent charges to PLA surfaces. Therefore a copolymer of α,β-poly(N-2-hydroxyethyl)-DL-aspartamide bearing in the side chains ethylendiammine (EDA), carboxypropyl trimethylammonium (CPTA) groups and lipoic portions was synthesized (PHEA-EDA-CPTA-LA). In parallel, a hydrophobic “clickable” propargilated PLA94 surface was prepared according to a previously described procedure.[3] After proper reduction of the disulfide bridge, PHEA-EDA-CPTA-LA was conjugated to the propargilated PLA94 surface by photo-chemical reaction between free thiols and propargilic groups.
To confirm the covalent surface modification and quantify the density of surface functionalization, SEC and XPS analysis were performed. Further, it was investigated on the biocompatibility of PHEA-EDA-CPTA-LA modified PLA94 surfaces monitoring in vitro the proliferation of mouse fibroblasts
Evaluation of paclitaxel-releasing synthetic biodegradable vascular grafts for the prevention of intima hyperplasia
No full text
FUNCTIONALITATION OF HYDROPHOBIC SURFACES WITH A POLYASPARTAMIDE-BASED DERIVATIVE FOR BIOMEDICAL APPLICATION
No full textA convenient way for the achievement of polymer-based solid materials for specific biomedical applications is grafting the appropriate macromolecules onto the surfaces in order to confer them specific properties. To date many approaches have been used to covalently modify polymeric surfaces, and among them chemoselective coupling reactions, usually referred as “click” reactions, gained much attention thanks to simple procedure with high reaction rate under mild reaction conditions (at normal temperature and pressure). In particular, radical-initiated thiol-yne “photo-click” chemistry has been demonstrated as an effective way to functionalize efficiently surfaces. In this frame, copper catalysed “click” chemistry was recently used to confer antibacterial and antibiofilm properties to propargylated PLA surfaces by immobilization of polyquaternary ammoniums
Evaluation of paclitaxel-releasing synthetic biodegradable vascular grafts for the prevention of intima hyperplasia
No full textTOWARD POTENT ANTIBIOFILM DEGRADABLE MEDICAL DEVICES: GENERIC METHODOLOGIES FOR THE SURFACE MODIfiCATION OF POLYLACTIDE
No full textSurface 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
TOWARD POTENT ANTIBIOFILM DEGRADABLE MEDICAL DEVICES: GENERIC METHODOLOGIES FOR THE SURFACE MODIfiCATION OF POLYLACTIDE
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