Bisphosphonic acid groups are emerging as promising functionalities for actinide decontamination, due to their high density of chelating sites. However, the chemistry of bisphosphonate (in particular alendronate) materials remains complex and underexplored. Herein, the synthesis of novel valuable materials, namely poly(N-isopropylacrylamide)-b-poly(acryloylmorpholine-co-alendronate acrylamide) (PNIPAAm-b-P(NAM-co-AleAAm)) was reported. These copolymers were synthesized in three steps. First, poly(N-isopropylacrylamide)-b-poly(acryloylmorpholine-co-N-acryloxysuccinimide) (PNIPAAm-b-P(NAM-co-NAS)) diblock copolymers were prepared by RAFT polymerization. Then, bisphosphonic acid groups were grafted onto the preformed copolymers by a post-polymerization modification reaction. Original produced alendronate-based functional copolymers were either water-soluble or capable of forming hydrogels under suitable concentration and temperature conditions. Sorption properties of such materials for actinides were investigated. For such purpose, the binding affinities of these functionalized copolymers for actinide surrogates, Nd(III) and Ce(III), were evaluated by isothermal titration calorimetry (ITC). Experimental results demonstrated good complexation efficiency, which logically raised with increasing bisphosphonic acid content. These results highlight the potential of well-defined, tunable hydrosoluble/hydrogel bisphosphonate-based polymers as high potential candidates for actinide decorporation applications.

Cancer remains one of the most significant global health challenges, with surgery representing the primary therapeutic approach for most solid tumors. However, the risk of local recurrence due to residual tumor cells necessitates the development of innovative strategies that can provide localized, controlled treatment. This study presents multifunctional electrospun scaffolds based on a poly(ε-caprolactone)-graft-polydopamine (PCL-g-PDA) copolymer blended with polylactic acid (PLA) and loaded with doxorubicin (DOX). Plasma treatment significantly improved the surface wettability of the scaffold. Morphological and physicochemical analyses confirmed the formation of homogeneous fibres. The presence of PDA side chains results in a notable photothermal response when exposed to near-infrared (NIR) light, reaching hyperthermic temperatures of up to 48 °C. Release studies revealed controlled pH-responsive kinetics that were further accelerated by NIR exposure and subsequent thermal activation. In vitro assays on HCT-116 colorectal cancer cells cultured in 2D and 3D revealed enhanced cytotoxic effects resulting from the combination of chemotherapy and photothermal therapy. These results demonstrate the significant potential of the PLA/PCL-g-PDA + DOX scaffold as a smart and multifunctional therapeutic platform for localized, potential post-surgical cancer treatment. It effectively combines chemotherapy and hyperthermia to minimize the risk of recurrence.

Freeze-casting enables the fabrication of porous scaffolds for bone reconstruction, but the homogeneous dispersion of bioactive glass (BG) in polymer solutions remains challenging. Here, we report, for the first time, the synthesis of core-shell microparticles combining Cu-doped BG with poly(D,L-lactide) (PDLLA) grafted via a surface-initiated "grafting from" approach. Covalent grafting was confirmed by FT-IR spectroscopy and TGA analyses, with grafted chain lengths close to theoretical values. In simulated body fluid (SBF), the PDLLA corona temporarily delayed glass degradation and ion release, mitigating the initial "burst effect", particularly for Cu2+. In vitro, all samples displayed dose-dependent antibacterial and cytotoxic responses, but PDLLA-grafted particles improved cell viability while preserving antibacterial activity. Notably, PDLLA-BG5 achieved the best balance between bacterial inhibition and cytocompatibility. These polymer-grafted, Cu-doped BG microspheres represent promising candidates as building blocks for future PDLLA-based scaffold fabrication via freeze-casting approaches, with scalable processing and tuneable ion-release-driven biological responses.

Binary SiO2-CaO bioactive glass nanoparticles (NPs) are synthesized as the elementary bricks of freeze-cast (FC) macroscopic scaffolds envisioned for human mandible bone transplants. In-situ X-ray scattering at ultra-small, small and wide angles (USAXS/SAXS/WAXS) was used to monitor the successive steps involved in the production of the NPs and their stability in suspensions prior to FC. Time-resolved scattering (TR-SAXS) revealed the growth mechanisms of nanosilicate cores in aqueous solutions. Quantitative analysis in absolute scale of the intensity demonstrates that subsequent calcium incorporation strongly modifies the colloidal interactions via the formation of hydrated Ca & sup2;(+)/NO3- interfacial layers, that promote partial mass-fractal aggregation from reduced electrostatic repulsion. Upon transfer to organic FC solvents such as dimethyl carbonate, further ion condensation favors tenuous rod-like aggregation even for pure silica NPs. SAXS analysis combined with analytical centrifugation indicate that aggregation controls the homogeneity of the FC suspensions by greatly accelerating sedimentation, which can be mitigated by addition of free PDLLA chains. Operando phase-contrast X-ray computed tomography prior to FC further reveals the spatial NPs and aggregates distribution, that strongly influence the properties of the final scaffold network. This comprehensive multiscale framework linking nanoparticle synthesis and interactions, colloidal stability and FC suspensions homogeneity, provides new insights for the rational design of freeze-cast nanocomposite scaffolds.

Bisphosphonate-functionalized copolymers were prepared through a two-step synthetic procedure to develop materials with enhanced metal coordination capabilities. Initially, poly(oligo(ethylene glycol) methyl ether methacrylate-co-methacrylic acid) (P(OEGMA-co-MAA)) copolymers were synthesized via reversible additionfragmentation chain transfer (RAFT) polymerization. By varying the molecular weight (20000 or 60000 g. mol-1) and OEGMA/MAA molar ratio, a range of copolymers was obtained with controlled molecular characteristics. Optimal RAFT conditions, using a [AIBN]/[CTA] molar ratio of 0.5/1, enabled high monomer conversion rates while maintaining narrow dispersity. The random incorporation of monomers was confirmed by kinetic studies and the determination of reactivity ratio. In the second step, bisphosphonate functionalities were introduced by achieving EDC/NHS coupling reaction in the presence of alendronate sodium to afford P(OEGMAco-MAA-co-AleMAAm) copolymers. The successful functionalization was confirmed by 1H and 31P NMR spectroscopy. Finally, complexation properties toward neodymium (III) cations, surrogates of actinides, were determined as a function of OEGMA/MAA molar ratio, alendronate functionalization rate, and copolymer molecular weight. Best neodymium (III) sorption dealt with the complexation of 47.3 mg of Nd(III) ions per gram of P(OEGMA25-co-MAA65-co-AleMAAm10)60k copolymer. This result is of great interest, as it shows that optimized synthesized materials are more efficient than most of the materials reported to date in the literature for the complexation of Nd(III) cations, thus opening the way to their use for application in actinide decontamination.

In this study, the polysaccharides isolated from Matthiola longipetala (PSMT) purified by DEAE-Sepharose chromatography. Two fractions of polysaccharides, PSMT1 and PSMT2 were obtained. The PSMT1 and PSMT2 structures and physicochemical properties were investigated using chemical and instrumental analysis, including Fourier transform infrared (FT-IR) spectroscopy, spectrum visible UV, nuclear magnetic spectroscopy (1H-NMR and 13C-NMR), X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). The results of high-performance liquid chromatography (HPLC-MS) showed that the both purified polysaccharides PSMT1 and PSMT2 were mainly composed of rhamnose, arabinose, glucose and galactose in a molar percent in 39.69

Silicate-based bioactive glass nano/microspheres hold significant promise for bone substitution by facilitating osteointegration through the release of biologically active ions and the formation of a biomimetic apatite layer. Cu-doping enhances properties such as pro-angiogenic and antibacterial behavior. While sol-gel methods usually yield homogeneous spherical particles for pure silica or binary glasses, synthesizing poorly aggregated Cu-doped ternary glass nano/microparticles without a secondary CuO crystalline phase remains challenging. This article introduces an alternative method for fabricating Cu-doped ternary microparticles using sol-gel chemistry combined with spray-drying. The resulting microspheres exhibit well-defined, poorly aggregated particles with spherical shapes and diameters of a few microns. Copper primarily integrates into the microspheres as Cu0 nanoparticles and as Cu2 + within the amorphous network. This doping affects silica network connectivity, as calcium and phosphorus are preferentially distributed in the glass network (respectively as network modifiers and formers) or involved in amorphous calcium phosphate nano-domains depending on the doping rate. These differences affect the interaction with simulated body fluid. Network depolymerization, ion release (SiO4 4-, Ca2 + , PO4 3-, Cu2 + ), and apatite nanocrystal layer formation are impacted, as well as copper release. The latter is mainly provided by the copper involved in the silica network and not from metal nanoparticles, most of which remain in the microspheres after interaction. This understanding holds promising implications for potential therapeutic applications, offering possibilities for both short-term and long-term delivery of a tunable copper dose.

Copolymers of poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) are widely used in biomedical applications. As inactive ingredients in formulations, tracking their degradation byproducts in vivo stands as a major challenge but is a pivotal endeavor to ensure safety and further progress in clinical stages. Current bioanalytical methods used to monitor this degradation lack sensitivity and quantification precision. This study introduces a cost-effective synthetic route for 13C-labeled PEG-PLA copolymers, combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), to monitor their in vitro and ex vivo degradation. Incorporating 13C isotopes into copolymers significantly enhances MALDI-TOF sensitivity, allowing for precise detection of degradation products at exceedingly low concentrations. We demonstrate the ability to trace 13C-labeled PEG-PLA in complex biological media (urine, plasma) at concentrations 100 times lower than labeled PEG-PLA. Our results pave the way toward ultrasensitive in vivo tracking and elucidation of in vivo fate of this widely investigated polymer family.

Original α-aminobisphosphonate-based copolymers were synthesized and successfully used for actinide complexation. For this purpose, poly(α-chloro-ε-caprolactone-co-ε-caprolactone)-b-poly(ethylene glycol)-b-poly(α-chloro-ε-caprolactone-co-ε-caprolactone) copolymers were first prepared by ring-opening copolymerization of ε-caprolactone (εCL) and α-chloro-ε-caprolactone using poly(ethylene glycol) (PEG) as a macro-initiator and tin(II) octanoate as a catalyst. The chloride functions were then converted to azide moieties by chemical modification, and finally α-aminobisphosphonate alkyne ligand (TzBP) was grafted using click chemistry, to afford well-defined poly(αTzBPεCL-co-εCL)-b-PEG-b-poly(αTzBPεCL-co-εCL) copolymers. Three copolymers, showing different α-aminobisphosphonate group ratios, were prepared (7, 18, and 38%), namely, CP8, CP9, and CP10, respectively. They were characterized by 1H and 31P NMR and size exclusion chromatography. Sorption properties of these copolymers were evaluated by isothermal titration calorimetry (ITC) with neodymium [Nd(III)] and cerium [Ce(III)] cations, used as surrogates of actinides, especially uranium and plutonium, respectively. ITC enabled the determination of the full thermodynamic profile and the calculation of the complete set of thermodynamic parameter (ΔH, TΔS, and ΔG), with the Ka constant and the n stoichiometry. The results showed that the number of cations sorbed by the functional copolymers logically increased with the number of bisphosphonate functions borne by the macromolecular chain, independently of the complexed cation. Additionally, CP9 and CP10 copolymers showed higher sorption capacities [21.4 and 34.0 mg·g-1 for Nd(III) and 9.6 and 14.3 mg·g-1 for Ce(III), respectively] than most of the systems previously described in the literature. CP9 also showed a highest binding constant (7000 M-1). These copolymers, based on non-toxic and biocompatible poly(ε-caprolactone) and PEG, are of great interest for external body decontamination of actinides as they combine high number of complexing groups, thus leading to great decontamination efficiency, and limited diffusion through the skin due to their high-molecular weight, thus avoiding additional possible internal contamination.

Original carboxylic acid-based copolymers have been developed for the complexation of actinides. For such purpose, ring-opening copolymerizations of a-benzyl carboxylate-e-caprolactone (BzCL) and e-caprolactone (eCL) have been carried out with poly(ethylene glycol) (PEG) as macro-initiator and tin(II) octanoate, as catalyst, to afford poly(eCL-st-aBzeCL)-b-PEG-b-poly(eCL-st-aBzeCL) (PB) copolymers. Three different eCL/BzCL ratios were targeted (90/10, 75/25 and 50/50), leading to PB10%, PB25% and PB50%, respectively. Then, hydrogenation of the prepared copolymers allowed the deprotection of benzyl esters to carboxylic acids groups, leading to poly (eCL-st-aCOOHeCL)-b-PEG-b-poly(eCL-st-aCOOHeCL) copolymers (PA10%, PA25% and PA50%). All materials were fully characterized by 1H NMR, 13C NMR and size exclusion chromatography. Experimental ratios were found to be close from theoretical ones as equal to 92/08, 75/25, and 60/40. Molecular weight was the same for all copolymers (4000 g.mol(-1)). Complexing properties of the different copolymers were studied by Isothermal Titration Calorimetry (ITC) with neodymium (Nd(III)) and cerium (Ce(III)), used as actinide surrogates. ITC enabled the determination of the full thermodynamic profile (AG, AH, TAS, Ka, and stoichiometry). The results showed that PA25% was the polymer with the highest sorption capacity (13.6 mg.g(-1) for Nd(III) and 13.7 mg.g(-1) for Ce(III)) and the highest binding constant (8500 M-1 and 5500 M-1 for Nd(III) and Ce(III), respectively). This demonstrated that by increasing the amount of complexing carboxylic acid functions, the complexing capacity did not necessarily increase as well, reaching a maximum with PA25%. In a more general manner, all developed copolymers are very promising for cation complexation.

Protein-polymer bioconjugates have shown great promise in biomedical and life science applications including drug delivery and diagnosis. The current bioconjugation strategies suffer from lack of efficiency and versatility. In this article, poly(styrene-alt-maleic anhydride) copolymers were first prepared by RAFT polymerization and characterized by different analytical techniques. Then, the poly(styrene-alt-maleic anhydride) precursors were functionalized with primary amine such as azidopropylamine and amino poly(ethylene glycol). The reaction of amino compounds with maleic anhydride was found to be a highly efficient, a versatile, and a facile chemical ligation reaction for the synthesis of macromolecules with quantitative yield under mild conditions. The main benefit is the incorporation of a wide range of functionality by easily changing the primary amine compound. For the amphiphilic graft copolymers based on poly(ethylene glycol), aggregation behavior in water was investigated. In a second part, azido-functionalized polystyrene copolymers were used to prepare a new protein-polymer bioconjugate by copper-free click chemistry reaction.

This work reports on a novel polyester copolymer containing poly(dopamine), a synthetic analogue of natural melanin, evaluated in a sustained-release drug delivery system for ocular intravitreal administration of drugs. More specifically, a graft copolymer of poly(ε-caprolactone)-graft-poly(dopamine) (PCL-g-PDA) has been synthesized and was shown to further extend the drug release benefits of state-of-the-art biodegradable intravitreal implants composed of poly(lactide) and poly(lactide-co-glycolide). The innovative biomaterial combines the documented drug-binding properties of melanin naturally present in the eye, with the established ocular tolerability and biodegradation of polyester implants. The PCL-g-PDA copolymer was obtained by a two-step modification of PCL with a final PDA content of around 2-3 wt % and was fully characterized by size exclusion chromatography, NMR, and diffusion ordered NMR spectroscopy. The thermoplastic nature of PCL-g-PDA allowed its simple processing by hot-melt compression molding to prepare small implants. The properties of unmodified PCL and PCL-g-PDA implants were studied and compared in terms of thermal properties (differential scanning calorimetry), thermal stability (thermogravimetry analysis), degradability, and in vitro cytotoxicity. PCL and PCL-g-PDA implants exhibited similar degradation properties in vitro and were both stable under physiological conditions over 110 days. Likewise, both materials were non-cytotoxic toward L929 and ARPE-19 cells. The drug loading and in vitro release properties of the new materials were investigated with dexamethasone (DEX) and ciprofloxacin hydrochloride (CIP) as representative drugs featuring low and high melanin-binding affinities, respectively. In comparison to unmodified PCL, PCL-g-PDA implants showed a significant extension of drug release, most likely because of specific drug-catechol interaction with the PDA moieties of the copolymer. The present study confirms the advantages of designing PDA-containing polyesters as a class of biodegradable and biocompatible thermoplastics that can modulate and remarkably extend the drug release kinetics thanks to their unique drug-binding properties, especially, but not limited to, for ocular applications.

Objectives: To systematically present and interpret the current literature on research and treatment perspectives for mandibular osteoradionecrosis (mORN) in the field of biomaterials.Material and methods: A systematic review of the literature using the "Synthesis without meta-analysis" (SWiM) methodology was performed on PubMed, Embase and Cochrane, focusing on the implanta-tion of synthetic biomaterials for bone reconstruction in mORN in humans and/or animal models. The primary endpoints were the composition, efficacy on mORN and tolerance of the implanted synthetic biomaterials.Results: Forty-seven references were obtained and evaluated in full-text by two assessors. Ten (8 in humans and 2 in animal models) met the eligibility criteria and were included for analysis. Materials most often comprised support plates or metal mesh (5 of 10 cases) in combination with grafts or syn-thetic materials (phosphocalcic ceramics, glutaraldehyde). Other ceramic/polymer composites were also implanted. In half of the selected reports, active compounds (molecules, growth factors, lysates) and/or cells were associated with the reconstruction material. The number of articles referring to implantation of biomaterials for the treatment of mORN was small, and the properties of the implanted biomaterials were generally poorly described, thus limiting a thorough understanding of their role.Conclusion: In preventing the morbidity associated with some reconstructive surgeries, basic research has benefitted from recent advances in tissue engineering and biomaterials to repair limited bone loss.(c) 2021 Elsevier Masson SAS. All rights reserved.

This paper focuses on an integrative "bricks-and-mortar" approach involving bioactive glass nanoparticles (bricks) covalently functionalized with a customized polymer (mortar) combined with the freeze-casting process. With the aim of obtaining a macroporous composite for bone substitution, composed of a spatially homogeneous assembly of nanoscale objects, we establish a method for the systematic elaboration of nanocomposite scaffolds. It was implemented through several steps from the synthesis of functionalized poly(D,L-lactide) (PDLLA) and SiO2-CaO binary bioactive glass nanoparticles (diameter around 164 nm) to the unidirectional freeze-casting process. The different stages include the first description of controlled PDLLA (M-n 8400 g.mol(-1)) grafting onto bioactive glass nanoparticle surfaces, their fine characterization and grafting quantification, and their mixing with free PDLLA chains (83 400 g.mol(-1)) during suspension formulation. This paper emphasizes the effect of the working temperature during the freeze-casting process on the multiscale spatial organization of resulting scaffolds such as the porosity morphology (lamellar and tubular), size (from 30 to 380 mu m), anisotropy, and orientation. In addition to porosity, our results demonstrate a rosary-like organization of PDLLA-grafted nanoparticles in pore walls. The higher homogeneity in the spatial distribution of grafted nanoparticles over the height of scaffolds and at a micron scale confirms the validity of the "bricks-and-mortar" concept to prevent or limit aggregation. In particular, this study highlights the correlation between nanoparticle functionalization and mechanical properties, especially the recovery rate after compression tests. These results lay the foundation for the development of tunable materials for bone substitution, via potential enhancement of bioactivity and cell colonization.

Présenter de manière systématique et interpréter les données actuelles de la littérature sur la recherche et les perspectives de traitement de l’ostéoradionécrose mandibulaire (ORM) dans le domaine des biomatériaux. Une revue systématique de la littérature selon la méthodologie SWiM a été effectuée sur Pubmed, Embase et Cochrane, avec pour thème l’implantation de biomatériaux synthétiques pour la reconstruction osseuse dans les cas d’ORM, chez l’homme et/ou sur modèle animal. Les critères de jugement principaux étaient la composition du biomatériau synthétique implanté, son efficacité sur l’ORM et sa tolérance. Quarante-sept références ont été obtenues par recherche bibliographique et évaluées en texte complet par double lecture. Parmi eux, 10 articles (huit chez l’homme et deux sur modèle animal) correspondant aux critères d’éligibilité ont été inclus dans l’étude et ont fait l’objet d’une analyse critique. Concernant les matériaux, les plaques de maintien/treillis métalliques étaient majoritairement utilisées (5 cas sur 10) en association avec des greffes ou des matériaux synthétiques (céramiques phosphocalciques, glutaraldéhyde). D’autres matériaux composites céramique/polymère ont également été implantés. Dans la moitié des articles retenus, des composés actifs (molécules, facteurs de croissance, lysats) et/ou des cellules étaient associés au matériau de reconstruction. Le nombre d’article faisant référence à l’implantation de biomatériaux pour le traitement de l’ORM restait faible et les propriétés des biomatériaux implantés étaient généralement peu décrites, limitant ainsi la compréhension fine de leur rôle. Afin d’éviter la morbidité de certaines chirurgies réparatrices, la recherche fondamentale bénéficie des récents progrès de l’ingénierie tissulaire et des biomatériaux pour combler des pertes de substance osseuses limitées.

This paper focuses on a new integrative “bricks‑and‑mortar" approach involving bioactive glass nanoparticles (bricks) covalently functionalized with a customized polymer (mortar) combined with the freeze‑casting process. With the aim to obtain a macroporous composite for bone substitution, constituted of a spatially homogeneous assembly of nanoscale objects, we established a method for the systematic elaboration of nanocomposite scaffolds. It was implemented through several steps, from the synthesis of functionalized poly(D,L‑lactide) (PDLLA) and SiO2-CaO binary glasses system bioactive nanoparticles to the unidirectional freeze‑casting process. The different stages include the first description of controlled PDLLA grafting onto bioactive glass nanoparticles surface, their fine characterization and grafting quantification, and their mixing with free PDLLA chains during suspension formulation. Beyond the proof of concept linked to the synthesis and association of PDLLA-grafted bioactive glass nanoparticles, this article emphasized the effect of the working temperature during the freeze-casting process on the multiscale spatial organization of resulting scaffolds such as the porosity morphology (lamellar and tubular), size, anisotropy and orientation but also their mechanical behavior. These results lay the foundation for the development of tunable materials for bone substitution, via potential enhancement of bioactivity and cell colonization.

Polyester-based composites with silica nanoparticles fillers are promising candidates as biomaterials due to improved mechanical and biological properties. However, nanofillers use generally leads to an inhomogeneous distribution inside the polymer matrix because of agglomeration, decreasing composites overall performances. In view of improving nanofillers dispersion, we developed a synthesis and characterization method to design poly(d,l-lactide)-grafted silica nanoparticles using “grafting to” method and to quantify the amount of grafted poly(d,l-lactide). Firstly, well-defined N-hydroxysuccinimide ester poly(d,l-lactide)s were synthesized through a new pathway. Then, amino-functionalized silica nanoparticles were grafted with those customized polyesters yielding an amide covalent bond between both reagents. Such PDLLA-grafted nanoparticles were precisely characterized and the grafting amount was quantified using a dual approach based on TGA and FTIR analysis. The synthesis and the characterization methods developed constitute a robust and reproducible way to design well-defined polymer-grafted silica nanoparticles that could be used as nanofillers in polymer matrix nanocomposites for biomedical applications.