Recovery Induced by the Implantation of Hydrogels following a Spinal Cord Injury : a Behavioral, Electrophysiological and Histological Study

Il n'existe actuellement aucun traitement efficace pour les patients présentant une blessure au niveau de la moelle épinière. Ce triste constat est, en partie, dû à la présente d'une cicatrice empêchant la repousse des tissus. Dans ce contexte, des biomatériaux (composés non-toxiques) pourraient être implantés afin de réduire la cicatrice en formation et de fournir un support de repousse aux fibres nerveuses. Parmi ces biomatériaux, certains semblent induire de nombreuses améliorations chez le rat. Nous avons renforcé ces résultats, à l'aide de techniques électrophysiologiques. De plus, nous avons développé un nouveau matériau dégradable afin de limiter toutes réactions délétères à long terme. Après avoir synthétisé notre matériau, combinant les qualités de dégradabilité de l'acide poly(lactique) et les propriétés mécaniques du poly(méthacrylate d'hydroxyéthyle), nous avons évalué ses différentes caractéristiques et ses effets thérapeutiques. Les résultats obtenus sont encourageants. Il serait maintenant intéressant de coupler notre biomatériau à des molécules bioactives ou à des cellules.Currently, there is no treatment for patients with spinal cord injury. This pessimistic statement is, in part, due to the presence of a scar that prevents tissue regrowth. In this context, biomaterials (non-toxic compounds) could be implanted in order both to reduce the scar formation and to provide a growth support for nervous fibers. Among those biomaterials, many seem to induce numerous benefic effects in the rat model. We confirmed these data by the use of electrophysiological techniques. In addition, we developed a new degradable material so as to limit any long term deleterious reactions. After having synthesized our material, combining the degradable quality of the poly(lactic acid) and the mechanical properties of the poly(hydroxyethyl methacrylate), we analyzed its different characteristics and its therapeutic effects. The obtained results are encouraging. Now, it would be interesting to couple bioactive molecules or cells with our biomaterial scaffold

Inputs of Macromolecular Engineering in the Design of Injectable Hydrogels Based on Synthetic Thermoresponsive Polymers

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Synthetic Polymer-based Electrospun Fibers: Biofunctionalization Strategies and Recent Advances in Tissue Engineering, Drug Delivery and Diagnostics

WOS:000436457400005Background: Over the last decades, synthetic polymer-based electrospun nano/microfibers have emerged as potent materials in crucial biomedical applications such as tissue engineering, drug delivery and diagnostics. This is mainly attributed to versatility and reproducibility of the electrospinning (ES) process, as well as the high surface- to-volume ratio of the generated nanostructures. Appropriate functionalization with dedicated biomolecules (i.e. cell adhesive peptides, therapeutic molecules, bio-probes) is a critical requirement for the performances of such materials in their related application. Methods: We report on the different chemical methodologies for preparing biofunctionalized synthetic polymer fibers, on the basis of two main approaches: biomolecule introduction after ES process (post-ES) and before ES (pre-ES). We then focused on the latest implications of such materials in areas of tissue engineering, drug delivery and diagnostics. Results: Th is review describes the numerous immobilization strategies (either covalent or non-covalent) developed for designing biofunctionalized fibers, as well as their impact on their properties in dedicated application. The inputs of advanced conjugation tools ("clickable" chemistries, PEG linkers) for biofunctionalization are also highlighted. In the light of the literature, it appears that increasing research efforts are now devoted to multifunctional character and fiber combination with other materials (hydrogels, inorganic particles, microfluidic devices) for improved and tunable performances. Conclusion: Owing to flexibility and robustness of ES process as well as advances in conjugation and polymer/material engineering, high degree of control over biofunctionalization can now be achieved, to fit as best as possible the requirements of the targeted application. The performances reached up to now augur well for the future of such class of materials

Functional recovery after repair of peroneal nerve gap using different collagen conduits

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Ultra-Fast Synthesis of Multivalent Radical Nanoparticles by Ring-Opening Metathesis Polymerization-Induced Self-Assembly

WOS:000462622700049We report the straightforward, time-efficient synthesis of radical core-shell nanoparticles (NPs) by polymerization-induced self-assembly. A nitroxide-containing hydrophilic macromolecular precursor was prepared by ring-opening metathesis copolymerization of norbornenyl derivatives of TEMPO and oligoethylene glycol and was chain-extended insitu with norbornene in ethanolic solution, leading to simultaneous amphiphilic block copolymer formation and self-assembly. Without any intermediate purification from the monomers to the block copolymers, radical NPs with tunable diameters ranging from 10 to 110 nm are obtained within minutes at room temperature. The high activity of the radical NPs as chemoselective and homogeneous, yet readily recyclable catalysts is demonstrated through oxidation of a variety of alcohols and recovery by simple centrifugation. Furthermore, the NPs show biocompatibility and antioxidant activity invitro

A new method to assess weight-bearing distribution after central nervous system lesions in rats

International audienceThe aim of the present study is to assess the relevance of weight-bearing distribution (DWB) measurement in freely moving rats after stroke and thoracic spinal cord injuries. Animals were divided in 2 experiments: (1) The middle cerebral artery occlusion-reperfusion (MCAO-r) experiment containing the MCAO group in which focal brain ischaemia was induced by transient MCA occlusion and (2) the thoracic hemisection experiment containing the TH group in which a spinal cord hemisection was performed at the T 10 level. A Control and respective Sham groups were also included in each experiment. Not only the pressure exerted by each paw was measured but also different ratios such as: (1) the sum of the right and the left forepaws was normalized by the sum of the right and the left hindpaws (F/H), (2) the left forepaw was normalized by the right forepaw (LF/RF), (3) the left hindpaw was normalized by the right hindpaw (LH/RH). Additionally, the times spent on 3 paws and on 4 paws were measured. Only the time spent on 4 paws was shorter in the MCAO group than in the Control (p < 0.001) and in the Sham (p < 0.01) groups. The LH/RH ratio of the TH group at the 1st week was lower (p < 0.01) than the pre-surgical value. Moreover, its F/H ratio was superior (p < 0.001) to the ones of the Control and the Sham groups. Our study indicates that DWB should be more frequently used to evaluate both the severity of central nervous system traumas and the effectiveness of pharmacological and/or rehabilitation strategies

Degradable and injectable hydrogel for drug delivery in soft tissues

International audienceInjectable hydrogels are promising platforms for tissue engineering and local drug delivery as they allow minimal invasiveness. We have here developed an injectable and biodegradable hydrogel based on an amphiphilic PNIPAAm-b-PLA-b-PEG-b-PLA-b-PNIPAAm pentablock copolymer synthesized by ring-opening polymerization/nitroxide-mediated polymerization (ROP/NMP) combination. The hydrogel formation at around 30 °C was demonstrated to be mediated by intermicellar bridging through the PEG central block. Such a result was particularly highlighted by the inability of a PEG-b-PLA-b-PNIPAAm triblock analog of the same composition to gelify. The hydrogels degraded through hydrolysis of the PLA esters until complete mass loss due to the diffusion of the recovered PEG and PNIPAAm/micelle based residues in the solution. Interestingly, hydrophobic molecules such as riluzole (neuroprotective drug) or cyanine 5.5 (imaging probe) could be easily loaded in the hydrogels’ micelle cores by mixing them with the copolymer solution at room temperature. Drug release was correlated to polymer mass loss. The hydrogel was shown to be cytocompatible (neuronal cells, in vitro) and injectable through a small-gauge needle (in vivo in rats). Thus, this hydrogel platform displays highly attractive features for use in brain/soft tissue engineering as well as in drug delivery

A Sacrificial PLA Block Mediated Route to Injectable and Degradable PNIPAAm-Based Hydrogels

Thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm)-based injectable hydrogels represent highly attractive materials in tissue engineering and drug/vaccine delivery but face the problem of long-term bioaccumulation due to non-degradability. In this context, we developed an amphiphilic poly(D,L-lactide)-b-poly(NIPAAm-co-polyethylene glycol methacrylate) (PLA-b- P(NIPAAm-co-PEGMA)) copolymer architecture, through a combination of ring-opening and nitroxide-mediated polymerizations, undergoing gelation in aqueous solution near 30 °C. Complete hydrogel mass loss was observed under physiological conditions after few days upon PLA hydrolysis. This was due to the inability of the resulting P(NIPAAm-co-PEGMA) segment, that contains sufficiently high PEG content, to gel. The copolymer was shown to be non-toxic on dendritic cells. These results thus provide a new way to engineer safe PNIPAAm-based injectable hydrogels with PNIPAAm-reduced content and a degradable feature

Acute Neuromuscular Adaptation at the Spinal Level Following Middle Cerebral Artery Occlusion-Reperfusion in the Rat

International audienceThe purpose of the study was to highlight the acute motor reflex adaptation and to deepen functional deficits following a middle cerebral artery occlusion-reperfusion (MCAO-r). Thirty-six Sprague-Dawley rats were included in this study. The middle cerebral artery occlusion (MCAO; 120 min) was performed on 16 rats studied at 1 and 7 days, respectively (MCAO-D1 and MCAO-D7, n = 8 for each group). The other animals were divided into 3 groups: SHAM-D1 (n = 6), SHAM-D7 (n = 6) and Control (n = 8). Rats performed 4 behavioral tests (the elevated body swing test, the beam balance test, the ladder-climbing test and the forelimb grip force) before the surgery and daily after MCAO-r. H-reflex on triceps brachii was measured before and after isometric exercise. Infarction size and cerebral edema were respectively assessed by histological (Cresyl violet) and MRI measurements at the same time points than H-reflex recordings. Animals with cerebral ischemia showed persistent functional deficits during the first week post-MCAO-r. H-reflex was not decreased in response to isometric exercise one day after the cerebral ischemia contrary to the other groups. The motor reflex regulation was recovered 7 days post-MCAO-r. This result reflects an acute sensorimotor adaptation at the spinal level after MCAO-r

Naphthalimide-Based Dyes as Photoinitiators under Visible Light Irradiation and their Applications: Photocomposite Synthesis, 3D printing and Polymerization in Water

International audienceIn this work, six new fluorescent dyes derived from the naphthalimide scaffold (Napht1–Napht6) were synthesized and used as high-performance photoinitiating systems (PISs) in two and three-component systems (combined with iodonium salt (Iod) and/or an electron donor amine (such as N-phenylglycine[NPG])) for the radical photopolymerization of acrylate and methacrylate monomers under visible light using a light-emitting diode at 405 nm. Markedly, these dyes were never synthesized before. In fact, these PISs showed high initiation efficiency with both demonstrating high final reactive function conversions and high polymerization rates. A further interest of our study is to determine the effect of the different substituents (chromophoric group) on the naphthalimide function, concerning the efficiency of initiation of the free radical polymerization. In order to improve the mechanical properties of the obtained polymers, these derivatives were also tested for the photopolymerization of a blend of acrylate/epoxy monomers (TA/EPOX); these latter properties were characterized by traction tests. To demonstrate the initiation efficiency of these dyes, several methods and characterization techniques were used, including steady state photolysis, real-time Fourier transform infrared spectroscopy, emission spectroscopy as well as cyclic voltammetry. In our study, these naphthalimides were used for the synthesis of photocomposites (one and multiple layers of glass fibres) using a UV@395 nm (4 W/cm2) conveyor, as well as in the preparation of 3D printed polymers. Markedly, one of the naphthalimide derivatives (Napht-4) can be used as a new high-performance water soluble photoinitiator for photopolymerization in water and hydrogel synthesis