PLA scaffolds production from Thermally Induced Phase Separation: effect of process parameters and development of an environmentally improved route assisted by supercritical carbon dioxide

In this work, a relatively large scale of PLA scaffolds was produced using thermally induced phase separation (TIPS) combined with a supercritical carbon dioxide (SC-CO2) drying step as a green alternative. For the TIPS step, the phase separation of PLA and 1,4-dioxane solvent was controlled by adjusting the process conditions such as the polymer concentration and molecular weight, the 1,4-dioxane solvent power and the cooling conditions. The scaffolds morphology was analyzed by scanning electron microscopy. Their structural and mechanical properties were correlated together with the possibility to tune them by controlling the process conditions. An environmental analysis using the Life Cycle Assessment (LCA) methodology confirmed a reduction of at least 50% of the environmental impact of the whole process using the SC-CO2 drying compared to the traditional freeze-drying technology. This work is the first known attempt to conduct the LCA methodology on TIPS process for the PLA scaffolds production

Interaction of gentamicin sulfate with alginate and consequences on the physico-chemical properties of alginate-containing biofilms

BACKGROUND: Alginate is one of the main extracellular polymeric substances (EPS) in biofilms of Cystic Fibrosis (CF) patients suffering from pulmonary infections. Gentamicin sulfate (GS) can strongly bind to alginate resulting in loss of pharmacological activity; however neither the mechanism nor its repercussion is fully understood. In this study, we investigated how GS modifies the alginate macromolecular network and its microenvironment. MATERIAL AND METHODS: Alginate gels of two different compositions (either enriched in guluronate units (G) or enriched in mannuronate units (M)) were crosslinked with Ca and exposed to GS at varying times and concentrations. The complexes formed were characterized via turbidimetry, mechanical tests, swelling assay, calorimetry techniques, nuclear magnetic resonance, Ca displacement, macromolecular probe diffusion and pH alteration. RESULTS: In presence of GS, the alginate network and its environment undergo a tremendous reorganization in terms of gel density, stiffness, diffusion property, presence and state of the water molecules. We noted that the intensity of those alterations is directly dependent on the polysaccharide motif composition (ratio M/G). CONCLUSION: Our results underline the importance of alginate as biofilm component, its pernicious role during antibiotherapy and could represent a potential macromolecular target to improve anti-infectious therapies

Development of an eco-friendly Thermal Induced Phase Separation (TIPS) process assisted by supercritical CO2 for the production of PLA scaffolds with tunable structural and mechanical properties

Many routes are nowadays utilized for the production of PLA scaffolds. In this study, a relative large scale of scaffolds was produced combining thermal induced phase separation and supercritical CO2 as a green alternative drying. The phase separation between polylactic acid and 1,4-dioxane was monitored by adjusting the process parameters such as the polymer concentration, the molecular weight, the solvent power and the cooling conditions. The morphologic changes occurring during the phase separation were analyzed by scanning electron microscopy. Structural and mechanical properties of scaffolds were correlated and it was possible to tune them depending on the process parameters. Moreover, an environmental analysis of the thermal induced phase separation (TIPS) process and the comparison between supercritical CO2 and the traditional freeze drying technologies were investigated. This work is the first known attempt to conduct the life cycle assessment (LCA) methodology on TIPS process and the polylactic acid scaffolds production. The results of the LCA have demonstrated that using supercritical-CO2 drying technology allows to reduce by at least 50 % the environmental impact of the whole process and to drastically diminish the production time

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

Controlled Anchoring of Iron-Oxide Nanoparticles on Polymeric Nanofibers: Easy Access to Core@Shell Organic-Inorganic Nanocomposites for Magneto-Scaffolds

Composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and polymers are largely present in modern (bio)materials. However, while SPIONs embedded in polymer matrices are classically reported, the mechanical and degradation properties of the polymer scaffold are impacted by the SPIONs. Therefore, the controlled anchoring of SPIONs onto polymer surfaces is still a major challenge. Herein, we propose an efficient strategy for the direct and uniform anchoring of SPIONs on the surface of functionalized-polylactide (PLA) nanofibers via a simple free ligand exchange procedure to design PLA@SPIONs core@shell nanocomposites. The resulting PLA@SPIONs hybrid biomaterials are characterized by electron microscopy (SEM and TEM) and EDXS analysis, to probe the morphology and detect elements present at the organic/inorganic interface, respectively. A monolayer of SPIONs with a complete and homogeneous coverage is observed on the surface of PLA nanofibers. Magnetization experiments show that magnetic properties of the nanoparticles are well-preserved after their grafting on the PLA fibers and that the size of the nanoparticles does not change. The absence of cytotoxicity, combined with a high sensitivity of detection in MRI both in vitro and in vivo make these hybrid nanocomposites attractive for the development of magnetic biomaterials for biomedical applications

First Approach on Transfection Ability of Novel Amphiphilic Water Soluble Degradable Poly(e-caprolactone)-g-Poly(L-lysine) Copolymers.

International audienceThe potential of novel amphiphilic water soluble and degradable poly(e-caprolactone)-g-poly(L-lysine) as carriers for DNA transfection has been investigated. Two graft copolymers having the same proportion of lysine units but different structures have been synthesized following two grafting techniques. The chemical composition of these copolymers, their expected architectures and their behaviours in aqueous solutions have been studied. The benefits resulting from the use of these degradable polycationic structures as well as their ability to form polyplexes are discussed. Finally, preliminary transfection assays of MCF-7 cells by pRL-TK plasmid using poly(e-caprolactone)-g-poly(L-lysine) copolymers as carriers are reported

Degradable 4D-printed hydration-driven actuators from a single family of amphiphilic star-shaped copolymers

Actuators are largely used in biomedical applications in the presence of sensitive live cells or biomolecules, which makes actuators triggered by water uptake highly appealing. Dual-material printing and hydration driven expansion is a method of choice to produce such actuators, but mostly rely of non-degradable polymers or on the combination of polymers of different nature that may lead to interface incompatibilities. To overcome this challenge, we report here on two photocrosslinkable resins based on a single family of degradable hydrophilic or hydrophobic star-shaped poly(ethylene glycol)-poly(lactide) copolymers. The two materials are first printed individually and characterized to ensure that their properties enable the printing of dual material objects by stereolithographic digital-light processing. Dual-materials actuators are then printed by sequential switching of the hydrophobic and hydrophilic resin baths. Objects of simple and complex shapes are easily obtained and exhibit rapid actuation (&lt;60 s) upon hydration. The swelling-induced shape changes are accurately reproduced by numerical modeling of the printed geometries using the obtained material swelling properties. This set of results offers new perspectives to develop 4D-printed temporary medical devices.</p