Specific Aptamer Functionalization of Dense Ceramic by Click Chemistry Towards Circulating Tumor Cells Apheresis.

BACKGROUND/AIM: Circulating tumor cells (CTC) are tumor cells which can be disseminated at distance of the primary tumor and form metastatic niche. Moreover, their quantity is an important parameter which can induce cluster metastasis. A solution, can be the creation of a system that allow the capture and elimination from the blood of patients by using the medical device developed which is an inert bioceramic functionalized by aptamer target to CTC. MATERIALS AND METHODS: Herein we develop chemical reactions to bind a modified MUC1 specific DNA aptamer on an alumina (Al2O3) dense ceramic surface. In fact, MUC1 biomarker is very present on the surface of tumor cells. RESULTS: The specific developed chemical reactions led to the covalent binding of the aptamer while preserving its biological characteristics. CONCLUSION: This functionalization of dense alumina would allow the potential capture of circulating tumor cells.

Use of a Porous Alumina Antibiotic-Loaded Ceramic to Treat Bone Defect and Bone Infection After Road Trauma.

To describe the use of a porous alumina ceramic loaded with antibiotics for the reconstruction of bilateral tibial fractures in a patient who presented with bone loss and infection after a motorcycle road injury. A 70-year-old man presented open fractures of his both tibiae (proximal involvement on the right side and diaphyseal on the left side). After initial treatment with multiple débridements and the placement of bilateral external fixators, he had bone loss to both tibiae and had developed infections of both legs with multiple organisms identified (Stenotrophomonas maltophilia, Enterobacter cloacae, and Pseudomonas aeruginosa). We used a porous alumina ceramic, designed according to the defects to fill. This ceramic was loaded with antibiotics (gentamicin and vancomycin). The goal was to obtain locally high concentrations of antibiotics to eradicate bacteria that could have remain in the surgical wound. Ceramic parts were placed 4 months after the trauma. Local antibiotic concentrations largely exceeded the pharmacological parameters for antibiotics efficacy. External fixators were removed 3 months after implantation. After a follow-up of more than 1 year, there is no relapse of infection, and the patient resumed walking while ceramic parts were left in place and that bone started colonizing ceramic parts. This ceramic that combines strength and the possibility of antibiotic loading allows thinking of new ways to treat infected fractures with bone loss. Indeed, its mechanical strength provides primary stability, and antibiotics make it possible to secure implantation in an infected area.

Advanced protocol to functionalize CaP bioceramic surface with peptide sequences and effect on murine pre-osteoblast cells proliferation.

To bring osteoinductive properties to calcium phosphate (CaP) bioceramics, a silicon-substituted hydroxyapatite was functionalized by integrin-adhesive cyclic-pentapeptides (c-(DfKRG)). A new two-step protocol was set up to immobilize peptides at low and controlled density on the ceramic surface and limit contamination by adsorbed molecules. To this aim, a spacer bearing c-(DfKRG)-S-PEG6-NHS molecule was synthesized and bonded to an organosilane previously covalently bonded to the ceramic surface. The functionalized ceramic was tested in vitro for MC3T3-E1 murine pre-osteoblasts. CaP ceramic surface retained good biological properties thanks to low density of bonded molecules preserving part of the bioactive CaP surface free of bioorganic molecules. The final SiHA-T-PEG6-S-c-(DfKRG) was shown to increase cell density and to improve proliferation. Furthermore, the use of a strong and stable covalent bond between inorganic and organic parts prevented early burst release of the peptide and increased the persistence of its bioactivity over time. So, this CaP ceramic associating c-(DfKRG) by covalent grafting could be considered as promising new biomaterials for bone tissue engineering.

Does low hydroxyl group surface density explain less bacterial adhesion on porous alumina?

BACKGROUND: Bacterial adhesion depends on surface materials. Recently it was suggested that ceramic-on-ceramic bearings could be less prone to infection than other bearings. We examined the possibility that porous alumina ceramic could be less susceptible to bacterial adhesion. HYPOTHESIS: As hydroxyl groups (OH) on material surface are a major factor governing the surface properties (for example: adsorption, first non-specific step of bacterial adhesion), we hypothesized that alumina had lower OH group density than other material. Thus, we asked (i) if bacterial adhesion was lower on alumina than on titanium alloy, stainless steel and polyethylene and (ii) if OH group density was also lower on alumina. MATERIAL AND METHODS: We performed (i) in vitro bacterial cultures on porous alumina, titanium, stainless steel and polyethylene using Staphylococcus aureus and Pseudomonas aeruginosa, known to adhere to surfaces. Bacterial cultures were done 3 times in duplicate for each material and each strain. Colony Forming Units (CFU) per cm2 were measured; (ii) Neutral red reagent helped obtaining OH density estimates using spacer arms. UV-visible spectrophotometry method with Neutral red test, reproduced twice for each surface, provided µg/cm2 measurements of OH density. RESULTS: There was significantly less P. aeruginosa adherent on porous alumina (2.25×104 CFU/cm2) than on titanium (4.27×105 CFU/cm2, p=0.01), on stainless steel (2.44×105 CFU/cm2, p=0.02) and on polyethylene (7.29×105 CFU/cm2, p<0.001). S. aureus was significantly less adherent on porous alumina (3.22×105 CFU/cm2) than on polyethylene (5.23×106 CFU/cm2, p=0.01), but there was no difference with titanium (1.64×106 CFU/cm2, p=0.08) and stainless steel (1.79×106 CFU/cm2, p=0.1). There was significantly lower Neutral red grafted on porous alumina (0.09µg/cm2) than on titanium (8.88µg/cm2, p<0.0001), on stainless steel (39.8µg/cm2, p=0.002) and on polyethylene (4.5µg/cm2, p<0.01). However, no correlation was found between bacterial adherence and OH group density. DISCUSSION: Bacterial adherence on porous alumina was lower than on other bearings. Although there were less surface OH groups on porous alumina, we failed establishing a statistical correlation between bacterial adherence and OH group density. LEVEL OF EVIDENCE: IV, in vitro study.

Antibacterial activity of a photosensitive hybrid cellulose fabric.

We report the preparation of a cellulose fabric bearing derivative protoporphyrin IX units covalently attached to the cellulose backbone of a fabric. Ce(IV) redox system radical polymerization was used to polymerize methacrylic acid (MAA) onto a cotton material and to obtain cotton-g-polyMAA. Attachment of the photosensitizer, a protoporphyrin IX (PpIX) amino derivative, on cotton-g-polyMAA was realized successfully by a classical peptidic covalent link. The modified surfaces were characterized by ATR-FTIR, DRUV, TGA, and SEM methods. Under visible light irradiation, protoporphyrinic cotton showed antibacterial activity against Staphyloccoccus aureus. This concept is very promising in the field of bacterial decontamination (sterile area, hospital equipment, etc.).

Alumina Biocompatibility.

Alumina (Al2O3) ceramic is widely used for medical devices and its biocompatibility is well known and is reported in articles and textbooks. However, finding proof of this assertion gathered over more than 40 years can be challenging. We performed a literature review about alumina biocompatibility to compile data from the literature. We searched for articles on the biocompatibility of alumina in relation to the ISO 10993-1 International Standard, which defines the biocompatibility of biomaterials. For every biological effect listed in the norm, such as cytotoxicity, sensitization, implantation, and genotoxicity, in vitro and in vivo tests in animals and humans did not reveal any abnormal biological response. Proof for the the well-known biocompatibility of alumina is summarized in this review.

Synthesis and characterization of new ruthenium N-heterocyclic carbene Hoveyda II-type complexes. Study of reactivity in ring closing metathesis reactions.

This manuscript describes the synthesis and structural study of new second generation Hoveyda-Grubbs catalysts: 1,3-dimesityl-acenaphthylenyl-4,5-imidazolin-2-ylidene (BIAN-NHC) ruthenium isopropoxybenzylidene dichloride and 1,3-bis(2,6-dimethylphenyl)-2,3-dihydro-1H-imidazole Cl(2)Ru(=CH-o-O-i-PrC(6)H(4)) . The electrochemical and catalytic behavior of these new complexes was compared with the conventional NHC carbene Hoveyda II IMes-type complexes and for ring closing metathesis reactions.