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.

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.

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.

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.

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.

Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections.

Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60µm, allowing for incorporation inside the macropores (100µm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25-30days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions.

Chitosan finishing nonwoven textiles loaded with silver and iodide for antibacterial wound dressing applications.

Polyethylene terephtalate (PET) and Polypropylene (PP) textiles are widely used in biomedical application such as wound dressings and implants. The aim of this work was to develop an antibacterial chitosan (CHT) coating activated by silver or by iodine. Chitosan was immobilized onto PET and PP supports using citric acid (CTR) as a crosslinking agent through a pad-dry-cure textile finishing process. Interestingly, depending on the CHT/CTR molar ratio, two different systems were obtained: rich in cationic ammonium groups when the CTR concentration was 1%w/v, and rich in anionic carboxylate groups when the CTR concentration was 10%w/v. As a consequence, such samples could be selectively loaded with iodine and silver nitrate, respectively.Both types of coatings were analyzed using SEM and FTIR, their sorption capacities were evaluated toward iodide/iodate anions (I(-)/IO3(-)) and the silver cations (Ag(+)) were evaluated using elemental analysis. Finally, in vitro evaluations were carried out to evaluate the cytocompatibility on the epithelial cell line. The silver loaded textile reported a stronger antibacterial effect against E.coli (5 log10 reduction) than toward S. aureus (3 log10) while the antibacterial effect of the iodide loaded textiles was limited to 1 log10 to 2 log10 on both strains.

Evaluation of sorption capacity of antibiotics and antibacterial properties of a cyclodextrin-polymer functionalized hydroxyapatite-coated titanium hip prosthesis.

Infection still present as one of common complications after total hip replacement (∼2.5%), which may cause serious outcomes. For preventing such risk, loading antibiotics onto implants for increasing local drug concentration at targeted sites could be a solution. This study aims at modifying the surface of hydroxyapatite (HA) coated titanium hip implant material (Ti-HA) with polymer of cyclodextrin (polyCD) for loading antibiotics, to achieve a sustained local drug delivery. Two widely applied antibiotics (tobramycin and rifampicin) in orthopedic surgery were loaded alone or in combination. The drug adsorption isotherm, drug release kinetics and drug's efficacy were thoroughly investigated. The results proved that polyCD coating significantly improved the affinity of both drugs to Ti-HA surface, while the mechanism of drug-polyCD interaction varies from the nature of drug, courtesy of the structural complex of polyCD. The advantage of dual-drug loading was highlighted by its strong efficacy against both Staphylococcus aureus and Enterobacter cloacae, which overcomes the limitation of mono-drug loading for an effective treatment against both bacterial strains. The prolonged antibacterial activity of antibiotic loaded Ti-HA-polyCD samples confirmed that polyCD could be a promising drug-delivery system, for sustained antibiotics release or other potential applications e.g., antimitotic agent release.

Simultaneous immobilization of heparin and gentamicin on polypropylene textiles: a dual therapeutic activity.

The aim of this work was to prepare a nonwoven polypropylene (PP) textile functionalized with bioactive molecules in order to improve simultaneously anticoagulation and antibacterial properties. The immobilization of either heparin (anticoagulation agent) or gentamicin (aminoglycoside class antibiotic) alone has already been proven to be effective on PP nonwoven textiles. In this work, we managed to go further, by immobilizing both heparin and gentamicin at the same time on one unique textile. A successive immersion in different heparin and gentamicin bathes successfully led to a dual drug coated textile, as confirmed by several characterization techniques (Fourier transform infrared-attenuated total reflectance, X-ray photoelectron spectroscopy, and scanning electron microscopy). The immobilization times were varied in order to determine the best compromise between cytocompatibility, anticoagulant effect, and antimicrobial activity. Short immersion times in gentamicin solutions confer very good antimicrobial activity to the textile and avoid cytotoxicity, whereas long immersion times in heparin solution were necessary to observe a significant anticoagulant effect.

Poly-cyclodextrin functionalized porous bioceramics for local chemotherapy and anticancer bone reconstruction.

The progress in bone cancer surgery and multimodal treatment concept achieve only modest improvement in the overall survival, due to failure in clearing out residual cancer cells at the surgical margin and extreme side-effects of adjuvant postoperative treatments. Our study aims to propose a new method based on cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a high local drug concentration with a sustained release profile and a better control of residual malignant cells via local drug delivery and promotion of the reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic molecules, can be incorporated into HA (bone regeneration scaffold) through thermal treatment. The parameters of polyCD treatment on the macroporous HA (porosity 65%) were characterized via thermogravimetric analysis. Good cytocompatibility of polyCD functionalized bioceramics was demonstrated on osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an anticancer agent (cisplatin) were respectively loaded on polyCD functionalized bioceramics for drug release test. The results show that polyCD functionalization leads to significantly improved drug loading quantity (30% more concerning gentamicin and twice more for cisplatin) and drug release duration (7 days longer concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study offers a safe and reliable drug delivery system for bioceramic matrices, which can load anticancer agents (or/and antibiotics) to reduce local recurrence (or/and infection).

Prolonged local antibiotics delivery from hydroxyapatite functionalised with cyclodextrin polymers.

Per-operative infection is a common complication for bone-graft surgery. Combining antiseptic agents with graft materials may offer a solution by increasing local drug concentration at target sites. Aiming to achieve a sustained local antibiotic (ATB) delivery for a widely applied bone substitute material - hydroxyapatite (HA), we attempted incorporating hydroxypropyl-beta-cyclodextrin polymer (polyHPbetaCD) into microporous HA via impregnating either in a CD monomers mixture solution or a pre-synthesized CD polymer solution, followed by thermal fixation processing. In such functionalised material (CD-HA), polyHPbetaCD could entrap ATBs and release them progressively. Infrared-spectroscopic analysis confirmed the presence of polyHPbetaCD in functionalised HA via both processing pathways; polyHPbetaCD functionalisation yields were quantitated by thermogravimetric analysis for optimising the processing regime. Ciprofloxacin (CFX) and vancomycin (VCM), commonly applied in orthopaedics, have been respectively loaded on CD-HA by dip-coating. For both ATBs, kinetic release test in phosphate buffered saline showed significantly increased initial-burst amount and prolonged release from CD-HA compared with those from non-functionalised HA. Encouragingly, ATBs loaded CD-HA also revealed a prolonged bacteriostatic activity against Staphylococcus aureus and progressively increased cytocompatibility to osteoblasts (MC3T3-E1). Overall, polyHPbetaCD functionalisation on HA could be an effective drug-delivery model for loading different drug molecules in prevention of infection.