Electrospun polycaprolactone (PCL) nanofibrous membranes loaded with 2 2 % w/w polymyxin B (PMB) were developed as biodegradable antimicrobial wound dressings using two different solvent systems: organic (dichloromethane/dimethylformamide, OS) and acidic (acetic acid/formic acid, Acid). The choice of solvent significantly influenced fiber morphology, polymer crystallinity, mechanical properties, and drug-release kinetics. Both membranes exhibited well-defined bead-free nanofibers with diameters in the sub-micron range and porosity > 85 %. PMB release showed a marked initial burst within the first hour (approximate to 35-55 % for OS membranes vs. approximate to 20-30 % for Acid membranes), followed by sustained diffusion over 7 days. Agar diffusion tests revealed strong antibacterial activity against Staphylococcus aureus (inhibition zone 1.5 mm for OS-PMB, growth inhibition under the sample for Acid-PMB) and Pseudomonas aeruginosa (5.0 mm and 0.6 mm, respectively), with no bacterial growth under any PMB-loaded samples. All membranes proved non-cytotoxic (> 80 % cell viability). The use of only two FDA-approved components, combined with a simple one-step electrospinning process and tunable release via solvent selection, offers a highly scalable and clinically translatable platform for the local delivery of polymyxin B in infected or at-risk wounds.

Soft polymer networks are attractive for drug-eluting medical implants because their elasticity mimics soft tissues, and their swelling enables drug loading. Although polyurethanes (PUs) are widely used for long-term implantation, concerns over their toxic isocyanate precursors motivated the development of nonisocyanate alternatives. We report elastic poly(propylene glycol)-polyoxazolidone (PPG-POx) networks prepared from bis(α-alkylidene cyclic carbonate) (BisαCC) via a three-step, catalyst-free strategy: (i) step-growth polyaddition of BisαCC with PPG diamines, forming poly(hydroxy-oxazolidone)s, (ii) easy thermal dehydration to produce poly(alkylidene oxazolidone), and (iii) thiol-ene photo-cross-linking with a trithiol. By varying the BisαCC spacer, PPG molecular weight, dehydration degree, and cross-linker ratio, the properties of the networks were evaluated. The most promising candidate demonstrated biocompatibility with human fibroblasts, hemocompatibility, and sustained release under physiological conditions of acetylsalicylic acid (ASA), chosen for its widespread use in cardiovascular prevention and its antiplatelet activity. These results position BisαCC-derived PPG-POx networks as bio- and hemocompatible isocyanate-free alternatives to polyurethanes for drug-eluting implants.

Synthetic porous scaffolds are key elements in tissue engineering (TE), requiring controlled porosity for cell colonization, along with a degradation rate aligned with tissue growth. While biodegradable polyester scaffolds are widely used in TE, they are primarily hydrophobic and suited for semirigid to hard tissue applications. This work broadens the scope of TE by introducing porous scaffolds made of polyphosphoesters (PPEs), degradable polymers with adaptable physicochemical properties. PPE hydrogels were shaped into 3D scaffolds using an emulsion templating method, yielding hydrophilic matrices with controlled porosity and tunable Young's moduli for soft tissues. Degradation assays at physiological pH confirmed the scaffolds' biodegradability. Cytotoxicity tests with PPE scaffolds showed excellent cell viability, while RGD functionalization further enhanced cell adhesion. Scaffold colonization, low inflammation, and angiogenesis were demonstrated in vivo through subcutaneous implantation of the scaffolds in mice and histological analysis. These results highlight PPE-based scaffolds as promising candidates for regenerative medicine.

The biocompatibility, tunable degradability and broad functionalities of polyphosphoesters and their potential for biomedical applications have stimulated a renewed interest from Chemistry, Medicinal Chemistry and Polymer Sciences. Commercial applications of polyphosphoesters as biomaterials are still hampered because of the time and resource-intensive sourcing of their corresponding monomers, in addition to the corrosive and sensitive nature of their intermediates and by-products. Here, we present a groundbreaking challenge for sourcing the corresponding cyclic phosphate monomers by a different approach. This approach relies on the use of continuous flow technologies to intensify the end-to-end preparation of cyclic phosphate monomers with a semi-continuous modular flow platform. The applied flow technology mitigates both safety and instability issues related to the more classical production of cyclic phosphate monomers. The first flow module allows safe synthesis of a library of cyclic chlorophosphite building blocks and features in-line 31P NMR real-time monitoring. After optimization on the microfluidic scale, this first module is successfully transposed toward mesofluidic scale with a daily throughput of 1.88 kg. Downstream of the first module, a second module is present, allowing the quantitative conversion of cyclic chlorophosphites with molecular oxygen toward chlorophosphate derivatives within seconds. The two modules are concatenable with a downstream semi-batch quench of intermediate chlorophosphate with alcohols, hence affording the corresponding cyclic phosphate monomers. Such a continuous flow setup provides considerable unprecedented advantages to safely and efficiently synthesize a library of versatile high value-added cyclic phosphate monomers at large scale. These freshly produced monomers can be successfully (co)polymerized, using either batch or flow protocols, into well-defined polyphosphoesters with assessed thermal properties and cytotoxicity.

Shape-memory elastomer composite (SMEC) sheets, made of a honeycomb structured electrospun poly(epsilon-caprolactone) (PCL) fiber mat embedded in a silicone (PDMS) elastomer, fold on themselves upon uniaxial traction. The self-folding of the composite sheet originates from a bi-layered structure obtained by a simple one-step impregnation process. Indeed, the impregnation of a structured PCL fiber mat by oily PDMS in a flat Teflon mold leads, after curing, to an asymmetric composite sheet made of one PDMS flat thin layer on the mold side and one rough PDMS/PCL composite layer on the other side due to specific affinities between the three polymers involved. The self-folded shape of such structured single sheet obtained upon uniaxial stretching and stress release is controlled by the honeycomb pattern orientation versus stretching direction, by the pattern size and by the applied uniaxial stretching stress. High shape recovery and robust shape memory cycling are also demonstrated by dynamic mechanical analysis. This innovative process based on the mat structuration allows a straightforward one-step fabrication of shape memory sheets, with a wide scope of tunable self-folded curvatures exhibiting efficient temperature shape recovery.

The synthesis and properties of hybrid poly(ε-caprolactone) (PCL)–poly(ethylene oxide) (PEO) covalent adaptable networks have been investigated.

Solid-state lithium batteries are considered one of the most promising battery systems due to their high volumetric energy density, in this work a flame retarded polymer electrolyte is proposed.

Poly(ethylene glycol)-b-polyphosphoester (PEG-b-PPE) block copolymer nanoparticles are promising carriers for poorly water soluble drugs. To enhance the drug loading capacity and efficiency of such micelles, a strategy was investigated for increasing the lipophilicity of the PPE block of these PEG-b-PPE amphiphilic copolymers. A PEG-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the drug loading with PEG-b-PPE bearing shorter pendant groups is reported evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, a first evidence of the biocompatibility of these novel PEG-b-PPE copolymers was achieved by performing cytotoxicity tests. The PEG-b-PPE derived by tocopherol was evidenced as particularly promising as delivery system of poorly water-soluble drugs.

Introduction: We hypothesised that the active targeting of v3 integrin overexpressed in neoangiogenic blood vessels and glioblastoma (GBM) cells combined with magnetic targeting of paclitaxel- and SPIO-loaded PLGA-based nanoparticles could improve accumulation of nanoparticles in the tumour and therefore improve the treatment of GBM.Methods: PTX/SPIO PLGA nanoparticles with or without RGD-grafting were characterised. Their in vitro cellular uptake and cytotoxicity was evaluated by fluorospectroscopy and MTT assay. In vivo safety and anti-tumour efficacy of different targeting strategies were evaluated in orthotopic U87MG tumour model over multiple intravenous injections.Results: The nanoparticles of 250nm were negatively charged. RGD targeted nanoparticles showed a specific and higher cellular uptake than untargeted nanoparticles by activated U87MG and HUVEC cells. In vitro IC50 of PTX after 48h was approximate to 1ng/mL for all the PTX-loaded nanoparticles. The median survival time of the mice treated with magnetic targeted nanoparticles was higher than the control (saline) mice or mice treated with other evaluated strategies. The 6 doses of PTX did not induce any detectable toxic effects on liver, kidney and heart when compared to Taxol.Conclusion: The magnetic targeting strategy resulted in a better therapeutic effect than the other targeting strategies (passive, active).

In the recent decades, biodegradable and biocompatible polyphosphoesters (PPEs) have gained wide attention in the biomedical field as relevant substitutes for conventional aliphatic polyesters. These amorphous materials of low glass transition temperature offer promise for the design of soft scaffolds for tissue engineering. Advantageously, the easy variation of the nature of the lateral pendant groups of PPEs allows the insertion of pendent unsaturations valuable for their further cross-linking. In addition, varying the length of the pendent alkyl chains allows tuning their hydrophilicity. The present work aims at synthesizing PPE networks of well-defined hydrophilicity and mechanical properties. More precisely, we aimed at preparing degradable materials exhibiting identical hydrophilicity but different mechanical properties and vice versa. For that purpose, PPE copolymers were synthesized by ring-opening copolymerization of cyclic phosphate monomers bearing different pendent groups (e.g., methyl, butenyl, and butyl). After UV irradiation, a stable and well-defined cross-linked material is obtained with the mechanical property of the corresponding polymer films controlled by the composition of the starting PPE copolymer. The results demonstrate that cross-linking density could be correlated with the mechanical properties, swelling behavior, and degradation rate of the polymers network. The polymers were compatible to human skin fibroblast cells and did not exhibit significant cytotoxicity up to 0.5 mg mL(-1). In addition, degradation products appeared nontoxic to skin fibroblast cells and showed their potential as promising scaffolds for tissue engineering.

Glioblastoma is the most frequent and aggressive primary malignant tumor of the central nervous system with a gloomy prognosis. Platinum derivatives and one among them, cisplatin, exhibited promising results when locally administered into the brain of glioblastoma bearing rats. Nanovectorization of anticancer agents through polymeric nanoparticles may even promote drug accumulation within cells, thus concentrating the drug efficiently at its target. Anchorage of gadolinium complexes on the corona of such smart drug delivery systems could further allow magnetic resonance imaging (MRI) monitoring of the nanoplatform biodistribution in the damaged parenchyma and its therapeutic benefit. For this purpose, a biocompatible amphiphilic triblock copolymer, made of degradable polyester and polycarbonate and bioeliminable polyethylene oxide (PEO), was synthesized by successive ring-opening polymerizations. After micellization in water, gadolinium complexes were grafted onto the PEO micelle corona and the carboxylate functions, located at the surface of the micelle's core, were able to cross-link with Pt(ii) complexes. A macromolecular prodrug was therefore recovered in which more than one third of the carboxylate functions were linked to a platinum atom. By this strategy, stable cisplatin cross-linked nanoparticles were formulated with a mean size in the range of 100.63 ± 12.04 nm consistent with biological investigations. Relaxometry measurements both in water and in plasma at 7 T, 25 °C, confirmed the intrinsic potential of these hybrid nanoparticles as alternative MRI contrast agents with a substantial increase in the r2/r1 ratio by a factor of 3.3 and 2.7, respectively, compared to the conventional low molar mass Gd-DTPA. As a result, their infusion within the striatum of glioblastoma-bearing mice resulted in a hypersignal on T2-weighted MR images that persisted over time. Ultimately, the formulated prodrug exhibited up to 50-fold increased accumulation in human glioblastoma cell lines and up to 32-fold enhanced subsequent Pt-DNA adduct formation in comparison with free cisplatin, thus supporting the potential of this innovative bimodal tool for further applications.

Sulindac loaded poly(HEMA) cross-linked microparticles were synthesized via one-pot free-radical dispersion polymerisation in supercritical carbon dioxide (scCO2) in presence of photocleavable diblock stabilisers based on polyethylene oxide (PEO) and poly(heptadecafluorodecyl acrylate) (PFDA) bearing a o-nitrobenzyl photosensitive junction (hv) (PEO-hv-PFDA), and ethylene glycol dimethacrylate (EGDMA) as cross-linker. Poly(HEMA) cross-linked microparticles either empty or sulindac loaded were obtained with well-defined spherical morphology with the sizes between 250 and 350 nm. Additionally, upon UV-photolysis the stabiliser on the surface was cleaved which permits to microparticles to be redispersed in water leading to water swollen microgels about 2.1-3.6 µm. Moreover, the release behaviour from obtained microgels indicated the sustained release of sulindac over 10 days. Besides, the surface modification after UV-photolysis was studied and proved that the particles can be functionalised with further chemistries.

Photochemically cross-linked shape-memory polymer (SMP) materials have been achieved by functionalizing chain-ends of star-shaped poly(epsilon-caprolactone) (PCL) with 7-hydroxypropoxy-4-methylcoumarin followed by photo-dimerization of these end-groups. The kinetics of the network formation in function of the photosensitizer concentration has been studied by swelling experiments and rheology. Thanks to the design of a dedicated homemade mold, highly reproducible irradiation conditions have been achieved allowing to study the network formation and properties, especially the shape memory properties, in relation to the coumarin dimerization degree as determined by Raman spectroscopy. In optimized conditions, PCL-based SMP materials exhibiting high fixity and recovery have been achieved in remarkably short irradiation time, typically 5 min. In addition, the precise control of the network cross-link density with the irradiation time, so as the high stability of the formed networks toward temperature variations was also demonstrated allowing the fine-tuning of the network properties by the irradiation process. Finally, the reversible character of the coumarin dimerization under light irradiation of appropriate wavelength has been quantified by Raman spectroscopy. The dimer photocleavage allows the photoreconfiguration of the networks offering the ability to modify the "permanent" shape of the SMP material, while preserving the excellent shape-memory properties.

OBJECTIVE:Periodontitis is an inflammatory disease that destroys the tooth-supporting attachment apparatus. Guided tissue regeneration (GTR) is a technique based on a barrier membrane designed to prevent wound space colonization by gingival cells. This study examined a new formulation composed of two polymers that could be photochemically cross-linked in situ into an interpenetrated polymer network (IPN) forming a hydrogel membrane. METHODS:We synthetized and characterized silanized hydroxypropyl methylcellulose (Si-HPMC) for its cell barrier properties and methacrylated carboxymethyl chitosan (MA-CMCS) for its degradable backbone to use in IPN. Hydrogel membranes were cross-linked using riboflavin photoinitiator and a dentistry visible light lamp. The biomaterial's physicochemical and mechanical properties were determined. Hydrogel membrane degradation was evaluated in lysozyme. Cytocompatibility was estimated by neutral red uptake. The cell barrier property was studied culturing human primary gingival fibroblasts or human gingival explants on membrane and analyzed with confocal microscopy and histological staining. RESULTS:The IPN hydrogel membrane was obtained after 120s of irradiation. The IPN showed a synergistic increase in Young moduli compared with the single networks. The CMCS addition in IPN allows a progressive weight loss compared to each polymer network. Cytocompatibility was confirmed by neutral red assay. Human cell invasion was prevented by hydrogel membranes and histological sections revealed that the biomaterial exhibited a barrier effect in contact with soft gingival tissue. SIGNIFICANCE:We demonstrated the ability of an innovative polymer formulation to form in situ, using a dentist's lamp, an IPN hydrogel membrane, which could be an easy-to-use biomaterial for GTR therapy.

Antimicrobial peptide loaded poly(2-hydroxyethyl methacrylate) particles were synthesized in supercritical carbon dioxide via one-pot free-radical dispersion polymerisation of 2-hydroxyethyl methacrylate and a cross-linker. Discrete particles with a well-defined spherical morphology and a diameter as low as 450 nm have been obtained in mild conditions. The encapsulation and release of the peptide were confirmed by antimicrobial tests that demonstrated for the first time a sustained release of the peptide from poly(2-hydroxyethyl methacrylate) microgels prepared by one-pot dispersion polymerization in supercritical carbon dioxide and then dispersed in water.

Polymer micelles have emerged as promising carriers for controlled release applications, however, several limitations of micelle-based drug delivery have also been reported. To address these issues, we have synthesized a functional biodegradable and cytocompatible block copolymer based on methoxypoly(ethyleneglycol)-b-poly(ε-caprolactone-co-α-azido-ε-caprolactone) (mPEG-b-poly(εCL-co-αN3εCL)) as a precursor of reduction sensitive core-crosslinked micelles. The synthesized polymer was formulated as micelles using a dialysis method and loaded with the anti-inflammatory and anti-cancer drug methotrexate (MTX). The micellar cores were subsequently crosslinked at their pendent azides by a redox-responsive bis(alkyne). The size distributions and morphology of the polymer micelles were assessed using dynamic light scattering (DLS) and transmission electron microscopy, and drug release assays were performed under simplified (serum free) physiological and reductive conditions. Cellular uptake studies in human breast cancer cells were performed using Oregon-green loaded core-crosslinked micelles. The MTX-loaded core-crosslinked micelles were assessed for their effects on metabolic activity in human breast cancer (MCF-7) cells by evaluating the reduction of the dye MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The apoptosis inducing potential of MTX-loaded core-crosslinked micelles was analysed using Hoechst/propidium iodide (PI) and annexin-V/PI assays. The data from these experiments indicated that drug release from these cross-linked micelles can be controlled and that the redox-responsive micelles are more effective carriers for MTX than non-crosslinked analogues and the free drug in the cell-lines tested.