Osteoinductive Bone Morphogenic Protein, Collagen Scaffold, Calcium Phosphate Cement, and Magnesium-Based Fixation Enhance Anterior Cruciate Ligament Tendon Graft to Bone Healing In Animal Models: A Systematic Review.

PURPOSE: To perform a systematic literature review to analyze the results of the in vivo animal models and strategies that use osteoinductive materials to enhance the tendon graft-bone interface for anterior cruciate ligament reconstruction (ACLR). METHODS: Following the Preferred Reporting Items for Systemic Reviews and Meta-Analysis guidelines, the PubMed, Embase, and Web of Science databases were searched. The inclusion criteria were studies of in vivo animal models of ACLR using a material to enhance tendon graft-bone interface healing and reporting at least the histologic results at the interface, along with radiologic and biomechanical data. Studies without control group or with another tendon-bone healing model were excluded. Methodologic quality was assessed with the Animal Research: Reporting In Vivo Experiments 1guidelines. RESULTS: Twenty-seven studies met the inclusion criteria. Rabbit was the main animal model of ACLR, along with sheep and dog models. ACLR procedures varied widely between studies.. The main promising strategies and materials were wrapping the material around the graft, with a collagen scaffold loaded with an osteoinductive molecule (mostly bone morphogenetic proteins). The second strategy consisted of injecting the material at the tendon-bone interface; calcium phosphate cement or a derivative were the most used materials. Finally, using osteoinductive fixation devices was the third strategy; magnesium-based interference screws seemed to show most favorable results. CONCLUSIONS: The studies retained had major methodologic flaws that limit the scope of these conclusions. However, based on histologic, biomechanical, and radiologic analyses, the most promising materials were a collagen scaffold loaded with an osteoinductive molecule and wrapped around the graft, calcium phosphate cement injected in the bone tunnel, and a magnesium-based fixation device. CLINICAL RELEVANCE: In vivo animal models have identified several promising strategies and materials to optimize the tendon-bone interface after ACLR, but standardized and reproducible assessments are needed before these strategies can be adopted clinically.

Poly(carboxylic acid)-Cyclodextrin/Anionic Porphyrin Finished Fabrics as Photosensitizer Releasers for Antimicrobial Photodynamic Therapy.

In the development of new antibacterial therapeutic approaches to fight multidrug-resistant bacteria, antimicrobial photodynamic therapy (aPDT) represents a well-known alternative to treat local infections caused by different microorganisms. Here we present a polypropylene (PP) fabric finished with citrate-hydroxypropyl-ßCD polymer (PP-CD) entrapping the tetra-anionic 5,10,15,20-tetrakis(4-sulfonatophenyl)-21H,23H-porphine (TPPS) as photosensitizer-eluting scaffold (PP-CD/TPPS) for aPDT. The concept is based on host-guest complexation of porphyrin in the cavities of CDs immobilized on the PP fibers, followed by its sustained and controlled delivery in release medium and simultaneous photoinactivation of microorganisms. Morphology of fabric was characterized by optical (OM) and scanning electron microscopies (SEM). Optical properties were investigated by UV-vis absorption, steady- and time-resolved fluorescence emission spectroscopy. X-ray photoelectron spectroscopy (XPS) and FT-IR revealed the surface chemical composition and the distribution map of the molecular components on the fabric, respectively. Direct 1O2 determination allowed to assess the potential photodynamic activity of the fabric. Release kinetics of TPPS in physiological conditions pointed out the role of the CD cavity to control the TPPS elution. Photoantimicrobial activity of the porphyrin-loaded textile was investigated against both Gram-positive Staphylococcus aureus ATCC 29213 (S. aureus) and Gram-negative Pseudomonas aeruginosa ATCC 27853 (P. aeruginosa). Optical microscopy coupled with UV-vis extinction and fluorescence spectra aim to ascertain the uptake of TPPS to S. aureus bacterial cells. Finally, PP-CD/TPPS fabric-treated S. aureus cells were photokilled of 99.98%. Moreover, low adhesion of S. aureus cells on textile was established. Conversely, no photodamage of fabric-treated P. aeruginosa cells was observed, together with their satisfying adhesion.

Development and Biological Evaluation of Inkjet Printed Drug Coatings on Intravascular Stent.

Inkjet-printing technology was used to apply biodegradable and biocompatible polymeric coatings of poly(d,l-lactide) with the antiproliferative drugs simvastatin (SMV) and paclitaxel (PCX) on coronary metal stents. A piezoelectric dispenser applied coating patterns of very fine droplets (300 pL) and inkjet printing was optimized to develop uniform, accurate and reproducible coatings of high yields on the stent strut. The drug loaded polymeric coatings were assed by scanning electron microscopy (SEM), atomic force microscopy (AFM), and transition thermal microscopy (TTM) where a phase separation was observed for SMV/PLA layers while PCX showed a uniform distribution within the polymer layers. Cytocompatibility studies of PLA coatings showed excellent cell adhesion with no decrease of cell viability and proliferation. In vivo stent implantation studies showed significant intrastent restenosis (ISR) for PCX/PLA and PLA plain coatings similar to marketed Presillion (bare metal) and Cypher (drug eluting) stents. The investigation of several cytokine levels after 7 days of stent deployment showed no inflammatory response and hence no in vivo cytotoxicity related to PLA coatings. Inkjet printing can be employed as a robust coating technology for the development of drug eluting stents compared to the current conventional approaches.

Cross-linked cyclodextrin-based material for treatment of metals and organic substances present in industrial discharge waters.

In this study, a polymer, prepared by crosslinking cyclodextrin (CD) by means of a polycarboxylic acid, was used for the removal of pollutants from spiked solutions and discharge waters from the surface treatment industry. In spiked solutions containing five metals, sixteen polycyclic aromatic hydrocarbons (PAH) and three alkylphenols (AP), the material exhibited high adsorption capacities: >99% of Co2+, Ni2+ and Zn2+ were removed, between 65 and 82% of the PAHs, as well as 69 to 90% of the APs. Due to the structure of the polymer and its specific characteristics, such as the presence of carboxylic groups and CD cavities, the adsorption mechanism involves four main interactions: ion exchange, electrostatic interactions and precipitation for metal removal, and inclusion complexes for organics removal. In industrial discharge waters, competition effects appeared, especially because of the presence of calcium at high concentrations, which competed with other pollutants for the adsorption sites of the adsorbent.

Systematic literature review of in vivo rat femoral defect models using biomaterials to improve the induced membrane technique: a comprehensive analysis.

Purpose: The aim of this study was to conduct a systematic literature review analyzing the results of in vivo rat femoral defect models using biomaterials for improving the induced membrane technique (IMT). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the PubMed, Embase, and Web of Science databases were searched. Inclusion criteria were studies reporting results of the IMT in in vivo rat femoral critical-sized defect models using a biomaterial possibly combined with molecules. Methodologic quality was assessed with the Animal Research: Reporting In Vivo Experiments guidelines. Results: Twenty studies met the inclusion criteria. Femoral stabilization with plate and screws was the most frequent. Histologic, biomechanical, and/or radiologic analyses were performed. In two-stage strategies, the PMMA spacer could be associated with bioactive molecules to enhance IM growth factor expression and improve bone formation. Modulating the roughness of spacers could increase IM thickness and accelerate its formation. In one-stage strategies, human tissue-derived membranes combined with bone grafting achieved bone formation comparable to a standard IMT. All calcium phosphate grafts seemed to require a functionalization with growth factors or bone marrow mononuclear cells to improve outcomes compared with non-functionalized grafts. Conclusion: This systematic review described the main parameters of the in vivo rat femoral defect models using biomaterials to improve the induced membrane technique. Although the studies included had several methodological limitations that may limit the scope of these conclusions, one- and two-stage strategies reported promising results with biomaterials to improve the IMT.

Evaluation of a Medical Grade Thermoplastic Polyurethane for the Manufacture of an Implantable Medical Device: The Impact of FDM 3D-Printing and Gamma Sterilization.

Three-dimensional printing (3DP) of thermoplastic polyurethane (TPU) is gaining interest in the medical industry thanks to the combination of tunable properties that TPU exhibits and the possibilities that 3DP processes offer concerning precision, time, and cost of fabrication. We investigated the implementation of a medical grade TPU by fused deposition modelling (FDM) for the manufacturing of an implantable medical device from the raw pellets to the gamma (γ) sterilized 3DP constructs. To the authors' knowledge, there is no such guide/study implicating TPU, FDM 3D-printing and gamma sterilization. Thermal properties analyzed by differential scanning calorimetry (DSC) and molecular weights measured by size exclusion chromatography (SEC) were used as monitoring indicators through the fabrication process. After gamma sterilization, surface chemistry was assessed by water contact angle (WCA) measurement and infrared spectroscopy (ATR-FTIR). Mechanical properties were investigated by tensile testing. Biocompatibility was assessed by means of cytotoxicity (ISO 10993-5) and hemocompatibility assays (ISO 10993-4). Results showed that TPU underwent degradation through the fabrication process as both the number-averaged (Mn) and weight-averaged (Mw) molecular weights decreased (7% Mn loss, 30% Mw loss, p < 0.05). After gamma sterilization, Mw increased by 8% (p < 0.05) indicating that crosslinking may have occurred. However, tensile properties were not impacted by irradiation. Cytotoxicity (ISO 10993-5) and hemocompatibility (ISO 10993-4) assessments after sterilization showed vitality of cells (132% ± 3%, p < 0.05) and no red blood cell lysis. We concluded that gamma sterilization does not highly impact TPU regarding our application. Our study demonstrates the processability of TPU by FDM followed by gamma sterilization and can be used as a guide for the preliminary evaluation of a polymeric raw material in the manufacturing of a blood contacting implantable medical device.

Antiviral functionalization of a polypropylene nonwoven textile structure as a self-decontaminating layer for respiratory masks.

The aim of this work was to develop a filtering biocidal polypropylene (PP) nonwoven textile structure to block and inactivate airborne bacteria and viruses. PP filters were functionalized with a cyclodextrin (CD)-polycarboxylic acid-crosslinked polymer (PP-CD) through a pad/dry/curing process, and were then activated by padding in an alkyl dimethyl benzalkonium chloride (ADBAC) solution. The textile finishing process parameters were optimized with the perspective of mass production, considering the threshold temperature necessary for provoking crosslinking and the limitation of the low thermal stability of PP. The use of an aqueous solution containing hydroxypropyl-ß-cyclodextrin (HPßCD), 1,2,3,4-butanetetracarboxylic acid (BTCA), ammonium hypophosphite (AH), and a surfactant allowed immobilization of the optimal quantity of cyclodextrin polymer under curing for 5 minutes at 125 °C without affecting the nonwoven PP structure. The presence of CD drastically increased the sorption of ADBAC on the textiles. There was leaching of ADBAC at the first rinsing and then satisfactory fastness at the second and third rinsings, revealing adsorption mechanisms by weak physical interactions, ionic interactions, and inclusion of ADBAC inside the CD cavities. SEM revealed no clogging of the nonwoven pores, nor any increase in the air flow resistance, as evaluated by pressure drop measurements. The filtration efficiency of particulate matter PM3.0 and PM0.5 was moderately affected, in contrast to that of PM0.3, which greatly decreased due to the loss of the electrostatic charge of the filter upon the functionalization process. Bactericidal tests resulted in a reduction of 3 log10 against Staphylococcus aureus, and for virucidal tests on human coronavirus HCoV-229E, there was a reduction of 3.4 log10, with both strains undergoing 20 minutes of contact. Finally, the filter we developed is manufacturable by a scalable process, and because of its filtration and biocidal performances, it is a choice material as a self-disinfecting layer in the fabrication of facepiece respirators.

Injectable Chitosan-Based Hydrogels for Trans-Cinnamaldehyde Delivery in the Treatment of Diabetic Foot Ulcer Infections.

Diabetic foot ulcers (DFU) are among the most common complications in diabetic patients and affect 6.8% of people worldwide. Challenges in the management of this disease are decreased blood diffusion, sclerotic tissues, infection, and antibiotic resistance. Hydrogels are now being used as a new treatment option since they can be used for drug delivery and to improve wound healing. This project aims to combine the properties of hydrogels based on chitosan (CHT) and the polymer of ß cyclodextrin (PCD) for local delivery of cinnamaldehyde (CN) in diabetic foot ulcers. This work consisted of the development and characterisation of the hydrogel, the evaluation of the CN release kinetics and cell viability (on a MC3T3 pre-osteoblast cell line), and the evaluation of the antimicrobial and antibiofilm activity (S. aureus and P. aeruginosa). The results demonstrated the successful development of a cytocompatible (ISO 10993-5) injectable hydrogel with antibacterial (99.99% bacterial reduction) and antibiofilm activity. Furthermore, a partial active molecule release and an increase in hydrogel elasticity were observed in the presence of CN. This leads us to hypothesise that a reaction between CHT and CN (a Schiff base) can occur and that CN could act as a physical crosslinker, thus improving the viscoelastic properties of the hydrogel and limiting CN release.

Core-Sheath Electrospun Nanofibers Based on Chitosan and Cyclodextrin Polymer for the Prolonged Release of Triclosan.

This work focuses on the manufacture of core-sheath nanofibers (NFs) based on chitosan (CHT) as sheath and cyclodextrin polymer (PCD) as core and loaded with triclosan (TCL). In parallel, monolithic NFs consisting of blended CHT-PCD and TCL were prepared. Nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier Transform Infrared spectroscopy (FTIR). SEM displayed the morphology of NFs and the structure of the nanowebs, while TEM evidenced the core-sheath structure of NFs prepared by coaxial electrospinning. The core diameters and sheath thicknesses were found dependent on respective flow rates of both precursor solutions. Nanofibers stability and TCL release in aqueous medium were studied and correlated with the antibacterial activity against Staphylococcus aureus and Escherichia coli. Results showed that the release profiles of TCL and therefore the antibacterial activity were directly related to the type of nanofibers. In the case of monolithic nanofibers, the NFs matrix was composed of polyelectrolyte complex (PEC formed between CHT and PCD) and resulted in a prolonged release of TCL and a sustained antibacterial effect. In the case of core-sheath NFs, the PEC was formed only at the core-sheath interface, leading to less stable NFs and therefore to a faster release of TCL, and to a less extended antibacterial activity compared to monolithic ones.

Polydopamine treatment of chitosan nanofibers for the conception of osteoinductive scaffolds for bone reconstruction.

We report the influence of treatment time of electrospun chitosan nanofibers (CHT NFs) in dopamine hydrochloride bath (2 mg.mL-1 in 10 mM Tris buffer, pH 8.5) on the extent of the polydopamine (pDA) coating on NFs surface. The reaction was characterized by FTIR and SEM analysis and the cytocompatibility of the scaffolds toward MT3C3-E1 cells was assessed. Biomimetic deposition of hydroxyapatite (HA) in 1.5xSBF batch was investigated by SEM-EDS and XRD. Samples treated in dopamine bath during 2 h promoted the structural stability of NFs in PBS, provided optimal cytocompatibility and induced the in vitro biomineralization from 6 days in 1.5xSBF. The XRD and SEM-EDS investigations confirmed formation of spherical-shaped particles composed of apatitic phase. Finally, this study shows that these NFs-pDA scaffolds prepared in the optimal experimental conditions defined here are promising candidates for application as osteoinductive scaffolds for bone regeneration applied to orthopedic and dental applications.

Electrospun Filtering Membrane Designed as Component of Self-Decontaminating Protective Masks.

The 2019 coronavirus outbreak and worsening air pollution have triggered the search for manufacturing effective protective masks preventing both particulate matter and biohazard absorption through the respiratory tract. Therefore, the design of advanced filtering textiles combining efficient physical barrier properties with antimicrobial properties is more newsworthy than ever. The objective of this work was to produce a filtering electrospun membrane incorporating a biocidal agent that would offer both optimal filtration efficiency and fast deactivation of entrapped viruses and bacteria. After the eco-friendly electrospinning process, polyvinyl alcohol (PVA) nanofibers were stabilized by crosslinking with 1,2,3,4-butanetetracarboxylic acid (BTCA). To compensate their low mechanical properties, nanofiber membranes with variable grammages were directly electrospun on a meltblown polypropylene (PP) support of 30 g/m2. The results demonstrated that nanofibers supported on PP with a grammage of around only 2 g/m2 presented the best compromise between filtration efficiencies of PM0.3, PM0.5, and PM3.0 and the pressure drop. The filtering electrospun membranes loaded with benzalkonium chloride (ADBAC) as a biocidal agent were successfully tested against E. coli and S. aureus and against human coronavirus strain HCoV-229E. This new biocidal filter based on electrospun nanofibers supported on PP nonwoven fabric could be a promising solution for personal and collective protection in a pandemic context.

How Adding Chlorhexidine or Metallic Nanoparticles Affects the Antimicrobial Performance of Calcium Hydroxide Paste as an Intracanal Medication: An In Vitro Study.

The aim of our study was to explore the potential value of metallic (Ag, Cu, and Zn) salts, polymer/metallic nanoparticles, and chlorhexidine (CHX) for improving the antimicrobial activity of calcium hydroxide (CH) against E. faecalis and C. albicans, associated with persistent endodontic infections. A first screening was performed by determining minimum inhibitory/bactericidal concentrations (MIC/MBC). Antimicrobial activity of the CH paste mixed with metallic salts, chitosan or cyclodextrin polymer metallic nanoparticles was compared to the antimicrobial activity of CH paste alone and CH + CHX using a time-kill kinetics assay. The effect of the antimicrobials on the rheological and the key mechanical properties were also examined. Copper and zinc were discarded because of their MIC/MBC values and silver because of its kill time curve profile. Except for a slower setting time after 24 h and a higher weight loss after 1 week of incubation, the mechanical behavior of the CH paste was unaffected by the addition of CHX. Polymeric/metallic nanoparticles failed to potentiate the antimicrobial effect of CH. By contrast, CHX increased this effect and thus could help eradicate E. faecalis associated with persistent root canal infections without altering the desired key physical properties of the CH paste.

In Vitro Microbiological and Drug Release of Silver/Ibuprofen Loaded Wound Dressing Designed for the Treatment of Chronically Infected Painful Wounds.

This study consisted of developing a dressing loaded with silver (Ag) and ibuprofen (IBU) that provides a dual therapy, antibacterial and antalgic, intended for infected painful wounds. Therefore, non-woven polyethyleneterephtalate (PET) textiles nonwovens were pre-treated by cyclodextrin crosslinked with citric acid by a pad/dry/cure process. Then, textiles were impregnated in silver solution followed by a thermal treatment and were then coated by Layer-by-Layer (L-b-L) deposition of a polyelectrolyte multilayer (PEM) system consisting of anionic water-soluble poly(betacyclodextrin citrate) (PCD) and cationic chitosan. Finally, ibuprofen lysinate (IBU-L) was loaded on the PEM coating. We demonstrated the complexation of IBU with native ßCD and PCD by phase solubility diagram and 1H NMR. PEM system allowed complete IBU-L release in 6 h in PBS pH 7.4 batch (USP IV). On the other hand, microbiological tests demonstrated that loaded silver induced bacterial reduction of 4 Log10 against S. aureus and E. coli and tests revealed that ibuprofen lysinate loading did not interfere with the antibacterial properties of the dressing.

Chitosan/Polycyclodextrin (CHT/PCD)-Based Sponges Delivering VEGF to Enhance Angiogenesis for Bone Regeneration.

Vascularization is one of the main challenges in bone tissue engineering (BTE). In this study, vascular endothelial growth factor (VEGF), known for its angiogenic effect, was delivered by our developed sponge, derived from a polyelectrolyte complexes hydrogel between chitosan (CHT) and anionic cyclodextrin polymer (PCD). This sponge, as a scaffold for growth factor delivery, was formed by freeze-drying a homogeneous CHT/PCD hydrogel, and thereafter stabilized by a thermal treatment. Microstructure, water-uptake, biodegradation, mechanical properties, and cytocompatibility of sponges were assessed. VEGF-delivery following incubation in medium was then evaluated by monitoring the VEGF-release profile and its bioactivity. CHT/PCD sponge showed a porous (open porosity of 87.5%) interconnected microstructure with pores of different sizes (an average pore size of 153 µm), a slow biodegradation (12% till 21 days), a high water-uptake capacity (~600% in 2 h), an elastic property under compression (elastic modulus of compression 256 ± 4 kPa), and a good cytocompatibility in contact with osteoblast and endothelial cells. The kinetic release of VEGF was found to exert a pro-proliferation and a pro-migration effect on endothelial cells, which are two important processes during scaffold vascularization. Hence, CHT/PCD sponges were promising vehicles for the delivery of growth factors in BTE.

Synthesis of novel catalytic composite nanofibers containing ruthenium nanoparticles stabilized by a citric acid-ß-cyclodextrin polymer.

The elaboration of catalytic composite nanofibers (NFs) by electrospinning through a one-pot strategy is described. First, aqueous colloidal suspensions of ruthenium nanoparticles (Ru NPs) formed by reduction of a Ru(iii) salt with NaBH4 and stabilized by poly(cyclodextrin citrate) (PCD) were prepared. Then, poly(vinyl alcohol) (PVA) of different molecular weights was dissolved in the colloidal suspensions that were electrospun. SEM analyses of the resulting nanowebs displayed uniform NFs, whose diameters ranged between 300 and 700 nm and enlarged upon increasing (i) PVA molecular weight, (ii) nanosuspension viscosity, (iii) the amount of NaBH4 and (iv) the PCD/Ru NP concentration. TEM analysis confirmed that Ru NPs with a mean diameter of around 2 nm were observed at the surface of NFs, embedded in the PVA matrix of NFs. HAADF-STEM and EDS mapping clearly showed that Ru NPs were homogeneously distributed onto and into the matrix of NFs. After their electrospinning, the prepared nanowebs were submitted to a heat post-treatment at 160 °C which was shown to trigger the PVA crystallization. In addition, the physical crosslinking of PVA chains by NaBO2 resulting from NaBH4 oxidation in the precursor suspension was also observed. Interestingly, an SEM study evidenced that the thermal post-treatment in combination with the presence of NaBO2 clearly improved the thermal stability of the synthesized composite nanowebs. Finally, catalytic hydrogenation tests showed the absence of Ru NPs leaching from NFs in the reaction medium, and displayed good conversion of styrene into ethylbenzene.

Release-killing properties of a textile modified by a layer-by-layer coating based on two oppositely charged cyclodextrin polyelectrolytes.

Infections represent a major medical concern and have severe impact on the public health economy. Antimicrobial coatings represent one major solution and are the subject of many investigations in academic and industrial research. Polyelectrolyte multilayers (PEMs) consist in the step-by-step deposition of polyanions and polycations films on surfaces. The wide range of disposable polyelectrolytes makes this approach among the most versatile methods as it allows to design surfaces that prevent bacterial adhesion, and kill bacteria by contact or by releasing antibacterial agents. The present work focused on the release-killing effect of an active PEM coating of a polyethylene terephthalate (PET) textile support. This activity was obtained thanks to the PEM film build up using cationic and anionic polyelectrolytes both based on cyclodextrins (PCD- and PCD+) that provided a reservoir property and prolonged release of triclosan (TCS). To this effect, a PET non-woven preliminarily modified with carboxylate groups by applying a thermofixation process was then treated by dip-coating, alternating soaking cycles in cationic PCD+ and in anionic PCD- solutions. Samples coated with such PEM film were then loaded with TCS whose release was assessed in dynamic mode in a phosphate buffered saline solution (PBS) at 37 °C. In parallel, TCS/PCD+ and TCS/PCD- interactions were investigated by Nuclear Magnetic Resonance (NMR) and phase solubility study, and the biocide activity was assessed against S. aureus and E. coli. Finally, the present study has demonstrated that our PCD+/PCD- PEM system presented release-killing properties that supplement the contact-killing effect of this system that was reported in a previous paper.

Stent coating by electrospinning with chitosan/poly-cyclodextrin based nanofibers loaded with simvastatin for restenosis prevention.

The main cause of failure of angioplasty stenting is restenosis due to neointimal hyperplasia, a too high proliferation of smooth muscle cells (SMC). The local and sustained delivery of selective pleiotropic drugs to limit SMC proliferation seems to be the hopeful solution to minimize this post surgery complication. The aim of this study is to develop a stent covered by nanofibers (NFs) produced by electrospinning, loaded with simvastatin (SV), a drug commonly used for restenosis prevention. NFs were prepared from the electrospinning of a solution containing SV and a mixture of chitosan (cationic) and ß-cyclodextrin (CD) polymer (anionic) which form together a polyelectrolyte complex that makes up the NFs matrix. First, the SV/CD interactions were studied by phase solubility diagram, DRX and DSC. The electrospinning process was then optimized to cover a self-expandable NiTiNOL stent and the mechanical resistance of the NFs sheath upon its introduction inside the delivery catheter was considered, using a crimper apparatus. The morphology, coating thicknesses and diameters of nanofibers were studied by scanning electron microscopy. The SV loading rates on the stents were controlled by the electrospinning time, and the presence of SV in the NFs was confirmed by FTIR. NFs stability in PBS pH 7.4 buffer could be improved after thermal post-treatment of NFs and in vitro release of SV in dynamic conditions demonstrated that the release profiles were influenced by the presence of CD polymer in NFs and by the thickness of the NFs sheath. Finally, a covered stent delivering 3 µg/mm2 of SV within 6 h was obtained, whose efficiency will be investigated in a further in vivo study.

Cyclodextrin polymers as efficient solubilizers of albendazole: complexation and physico-chemical characterization.

The inclusion behavior of natural cyclodextrins (CDs) and polymers based on natural cyclodextrins (CD-polymer), in solution and in solid-state, was studied towards a poorly water-soluble anti-helminthic drug, albendazole (ABZ), chemically methyl[5-(propylthio)-1-H-benzimidazol-2yl]carbamate. Drug-cyclodextrin solid systems were prepared by freeze-drying. Phase solubility study was used to evaluate the interaction in solution, between ABZ/(CDs) and ABZ/CD-polymers. The stability constants of ABZ/natural CDs and ABZ/CD-polymers complexes were calculated by phase solubility method. The apparent solubility of Albendazole was enhanced especially with poly alpha-CD. The formation of inclusion complexes with natural CDs and polymers of cyclodextrin in the solid-state form were confirmed by Fourier Fransform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR).

Influence of the Soluble⁻Insoluble Ratios of Cyclodextrins Polymers on the Viscoelastic Properties of Injectable Chitosan⁻Based Hydrogels for Biomedical Application.

Injectable pre-formed physical hydrogels provide many advantages for biomedical applications. Polyelectrolyte complexes (PEC) formed between cationic chitosan (CHT) and anionic polymers of cyclodextrin (PCD) render a hydrogel of great interest. Given the difference between water-soluble (PCDs) and water-insoluble PCD (PCDi) in the extension of polymerization, the present study aims to explore their impact on the formation and properties of CHT/PCD hydrogel obtained from the variable ratios of PCDi and PCDs in the formulation. Hydrogels CHT/PCDi/PCDs at weight ratios of 3:0:3, 3:1.5:1.5, and 3:3:0 were elaborated in a double⁻syringe system. The chemical composition, microstructure, viscoelastic properties, injectability, and structural integrity of the hydrogels were investigated. The cytotoxicity of the hydrogel was also evaluated by indirect contact with pre-osteoblast cells. Despite having similar shear⁻thinning and self-healing behaviors, the three hydrogels showed a marked difference in their rheological characteristics, injectability, structural stability, etc., depending on their PCDi and PCDs contents. Among the three, all the best above-mentioned properties, in addition to a high cytocompatibility, were found in the hydrogel 3:1.5:1.5. For the first time, we gained a deeper understanding of the role of the PCDi/PCDs in the injectable pre-formed hydrogels (CHT/PCDi/PCDs), which could be further fine-tuned to enhance their performance in biomedical applications.

A detailed analysis of the influence of ß-cyclodextrin derivates on the thermal denaturation of lysozyme.

The influence of HPßCD on the thermal denaturation of lysozyme was analyzed mainly from microcalorimetry and Raman investigations carried out in the molecular fingerprint and the low-frequency regions. It was shown that Raman spectroscopy investigations performed on a wide spectral range give the opportunity to describe the influence of HPßCD on the mechanism of protein denaturation. Using D2O as solvent allowed us to show that HPßCD mainly destabilizes the tertiary structure of lysozyme by enhancing the protein flexibility and thus inducing the destabilization of the secondary structure. Principal components analysis (PCA) was used for spectra treatment, providing important information about inclusion complex formation between protein hydrophobic residues and CDs molecules. Combining PCA and classical technics (curve fitting) of data analysis allowed a better understanding of the influence of HPßCD on the protein denaturation that seems to be related to the CDs capacity to form inclusion complex. It was observed that these interactions prevent the formation of new strong H-bonds between ß-sheet structures thereby inhibiting protein aggregation. This study reveals that CDs are promising systems for inhibiting protein aggregation without protein denaturation, only if designing derivative CDs is carefully controlled.