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Osteoarticular implants are designed to facilitate full recovery of lost function and ensure effective fixation of the implant. However, challenges may arise, resulting in implant failure, primarily attributed to infections at the implantation site and aseptic loosening. Thus, the surface of an implant must be altered to simultaneously offer osteoinductive and antibacterial properties. Synthetic hydroxyapatite (HAP) is frequently employed to modify metallic implant surfaces or serve as a bone filler material. To enhance its biocompatibility, HAP-based polymer composites were developed. Among most popular synthetic polymers, poly(vinyl alcohol) (PVA), is widely used because of its similar structure to the native extracellular matrix, along with chitosan (CS), a natural cationic polysaccharide, that shows biocompatibility, biodegradability and antimicrobial action, and could act as a carrier of antibacterial agents. The antibiotic of choice was Gentamicin (Gent), a water-soluble aminoglycoside, with very potent antibacterial activity for the treatment of wide range of infections, caused by Gram-negative and Gram-positive bacteria. The original approach of the presented research is the single-step electrophoretic deposition (EPD) on Ti plates of thus prepared biocomposite that would allow for on-site release of the drug. Obtained hydroxyapatite/chitosan/poly(vinyl alcohol/gentamicin (HAP/PVA/CS/Gent) biocomposite coating exhibited strong antibacterial effect against E. coli and S. aureus. Gentamicin release study indicated “burst” release in the first 48 h, with ~ 30% of total gentamicin released from the HAP/PVA/CS/Gent coating which is beneficial for the blockage of biofilm formation, followed by slow and steady release in the later period. Cytotoxic effect of HAP/PVA/CS/Gent coating was not pronounced in investigated MRC-5 and L929 cell lines. Also, in MRC-5 fibroblast cells, alkaline phosphatase levels doubled when in contact with HAP/PVA/CS/Gent, indicating good o

Zarastanje rana je složen proces koji uključuje koordinaciju između različitih tipova ćelija i odgovarajućeg mikrookruženja. Uprkos visokom regenerativnom potencijalu kože, defekti u vidu dubokih rana ili opekotina, teško spontano zarastaju i zahtevaju terapijski tretman. I pored napretka u bioinžinjeringu kože i intenzivnih istraživanja u cilju iznalaženja novih biomaterijala, lečenje hroničnih rana i dalje predstavlja aktuelan klinički problem. Hidrogelni zavoji, karakteristične porozne i hidratisane molekularne strukture, verno oponašaju mikrookruženje rane, te su se izdvojili kao obećavajuća alternativa i najbolji kandidati za stimulisanje procesa zarastanja. Hidrogelovi su bazirani na prirodnim i/ili sintetičkim polimerima, i u vidu trajnih ili privremenih zavoja podržavaju regeneraciju i zarastanje oštećene kože. Uvođenje nanotehnologije je omogućilo nove pristupe u sintezi i dobijanje in situ hibridnih hidrogelova, odličnih svojstava i prilagodljive funkcionalnosti. Istraživanja u cilju razvoja hidrogelnih zavoja sa mogućnošću procene mikrookruženja rane i prilagođenog tretmana na zahtev, predstavljaju ključ napretka u polju zbrinjavanja hroničnih rana. Pretklinička ispitivanja in vivo su neophodan uslov za finalnu karakterizaciju svakog novodizajniranog hidrogela. Ovaj rad razmatra prednosti upotrebe hidrogelnih zavoja i napretke u razvoju inteligentnih tretmana za rane sa odloženim zarastanjem. Takođe, jedan deo rada je posvećen proceni hidrogelova in vivo, kao i ključnoj ulozi veterinara tokom pretkliničkih ispitivanja na eksperimentalnim animalnim modelima.

This study presents comparison of our recently formulated two compartmental model with General fractional derivative (GFD) and Korsmeyer-Peppas, Makoid-Banakar and Kopcha diffusion models. We have used our GFD model to study the release of gentamicin in poly (vinylalcohol)/chitosan/gentamicin (PVA/CHI/Gent) hydrogel aimed for wound dressing in medical treatment of deep chronical wounds. The PVA/CHI/Gent hydrogel was prepared by physical cross linking of poly(vinyl alcohol)/chitosan dispersion using freezing-thawing method, and then was swollen for 48 h in gentamicin solution, at 37 °C. Different physico-chemical (FTIR, SEM), mechanical and biological (cytotoxicity, antibacterial activity) properties have been determined. The concentration of released gentamicin was determined using a high-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS). The ratio between concentration of released gentamicin and initial concentration of gentamicin in the hydrogel was monitored for the prolonged time period in order to obtain gentamicin release profile. It was proven that our novel diffusion GFD model better fitted with experimental data, and enabled the determination of diffusion coefficient precisely for the entire time period.

INTRODUCTION: Tissue engineering strives for innovative solutions in addressing challenges associated with contemporary bone tissue implants. This study focuses on the electrophoretic deposition (EPD) of hydroxyapatite-based bioceramic composites containing antibacterial agents onto titanium surfaces. Two composite coatings, hydroxyapatite/ chitosan (HAP/CS) and hydroxyapatite/chitosan/gentamicin (HAP/CS/Gent) were developed to combat issues such as poor adhesion, limited antibacterial potential, limited bioactivity, and potential toxicity of implant materials [1]. EXPERIMENTAL: EPD was performed at constant voltage (5 V, 12 min) on pure Ti plates from aqueous (HAP/CS and HAP/CS/Gent) suspensions. The uniformity and functionality of the deposited coatings were assessed through comprehensive physico-chemical characterization using X-ray diffraction (XRD) (Philips PW 1710, Netherlands) and scanning electron microscopy (SEM, Hitachi S-4700, J) equipped with energy dispersive X-Ray spectroscopy (EDS, X-Max, Oxford Instruments, UK). Antibacterial activity was evaluated against Staphylococcus aureus TL and Escherichia coli ATCC 25922 by quantitatively monitoring changes in the viable number of bacterial cells in suspension. Cytotoxicity against MRC-5 and L929 cell lines was investigated using trypan blue dye-exclusion test (DET) and MTT assay for assessing cell metabolic activity. Statistical significance was determined for antibacterial and cytotoxicity results by one-way analysis of variance (ANOVA), followed by multiple comparisons post-hoc test. RESULTS AND DISCUSSION: XRD revealed broadened diffraction maximums corresponding to fine HAP crystallites. Porous surface with homogeneously distributed spherical HAP agglomerates embedded in wax-like polymers' matrix of CS was observed for both coatings by SEM. The addition of gentamicin significantly enhanced the antibacterial activity of the HAP/CS/Gent coating – complete reduction of S. aureus bacterial cells was achieved

INTRODUCTION: Following orthopedic surgery, bacterial infection may lead to significant complications related to inflammation in the peri-implant region, including the potential for implant loosening. To address this concern, the surface of metallic implants was modified through the application of bioactive and antibacterial coatings, aiming to mitigate these issues. EXPERIMENTAL: HAP/PVA/CS/Gent coatings was single-step electrophoretically deposited from four-component aqueous suspension containing 1 wt.% hydroxyapatite powder (HAP, particles < 200 nm particle size, Sigma-Aldrich), 0.1 wt.% poly(vinyl alcohol) (PVA, medium molecular weight 89 to 98 kDa, 99 % hydrolysed, Sigma-Aldrich), 0.05 wt% chitosan powder (CS, medium molecular weight, 190 to 310kDa with 75 to 85 % deacetylation degree, Sigma-Aldrich), and aqueous gentamicin sulfate solution (Gent, concentration 50 mg/ml, Sigma-Aldrich) on titanium plates (Sigma-Aldrich). Antibacterial activity of HAP/PVA/CS/Gent coating was evaluated against Staphylococcus aureus TL (culture collection- FTM, University of Belgrade, Serbia) and Escherichia coli ATCC 25922, while kinetics of antibacterial activity was monitored according to our previously published data [1]. In vitro cytotoxicity assay was performed towards two fibroblast cell lines of different origin-mouse origin cell line (L929 (ATCC CRL-6364)) and human lung origin cell line (MRC-5 (ATCC CCL-171)) [2]. To evaluate the statistical significance of the biological assay results (antibacterial activity, cytotoxicity and ALP activity), one-way analysis of variance (ANOVA) followed by a multiple comparisons posthoc test was used. RESULTS AND DISCUSSION: HAP/PVA/CS/Gent coating exhibited strong antibacterial effect against both S. aureus and E. coli, especially pronounced against S. aureus, causing bactericidal effect. Cytotoxic effect of HAP/PVA/CS/Gent coating was not pronounced in investigated MRC-5 and L929 cell lines. MRC-5 fibroblast cells in contact with HAP

INTRODUCTION: Electrochemical methods were employed for synthesizing composites intended for applications in medicine as antibacterial coatings on titanium bone implants or as highly efficient antibacterial hydrogels for accelerated wound healing. EXPERIMENTAL: Hydroxyapatite-based coatings were single-step electrophoretically deposited from fourcomponent aqueous suspension containing 1 wt% hydroxyapatite powder (HAP, particles < 200 nm particle size, Sigma- Aldrich), 0.1 wt% poly(vinyl alcohol) (PVA, medium molecular weight, Sigma-Aldrich), 0.05 wt% chitosan powder (CS, medium molecular weight, Sigma-Aldrich), and aqueous gentamicin sulfate solution (Gent, concentration 50 mg/ml, Sigma-Aldrich) on titanium plates (Sigma-Aldrich). Antibacterial activity of HAP/PVA/CS/Gent coating was evaluated against Staphylococcus aureus TL (culture collection-FTM, University of Belgrade, Serbia) and Escherichia coli ATCC 25922. For poly(vinyl alcohol)/chitosan (PVA/CHI) hydrogel synthesis poly(vinyl alcohol) powder (PVA, Sigma Aldrich, USA), chitosan powder (CHI, Sigma Aldrich, USA), graphene (Graphene Supermarket, USA), glacial acetic acid (Beta Hem), silver nitrate (MP Hemija), potassium nitrate (Centrohem, Serbia) were used. For antibacterial properties evaluation, monobasic and dibasic (Sigma Aldrich, USA) potassium phosphates were used. Cell culture suspensions for cytotoxicity tests were prepared using MTT tetrazolium salt, EDTA, fetal calf serum and antibiotic-antimycotic solution (Sigma Aldrich, USA). RESULTS AND DISCUSSION: Surface modification of titanium with innovative bioactive coatings enhances biomineralization and reduces post-operation pain and infection risk. Using powerful single-step electrophoretic deposition (EPD) at a constant voltage we have produced various hydroxyapatite-based composite bioceramic coatings in combination with polymers (lignin, chitosan), graphene, and antibacterial agents (silver, gentamicin). Electrochemical methods enable in situ synth

U cilju poboljšanja bioaktivnosti i antibakterijskih svojstava metalnog implantata (titana), primenom elektroforetskog taloženja u jednom stupnju, iz četvorokomponentne vodene suspenzije dobijene su biokeramičke, kompozitne miltifunkcionalne prevlake na bazi hidroksiapatita, poli(vinil alkohola) i hitozana uz dodatak antibakterijskog agensa, antibiotika gentamicina. Na osnovu rezultata dobijenih FTIR, XRD i TG analizom pokazano je prisustvo karbonatno-supstituisanog hidroksiapatita (prisutnog i u prirodnom koštanom tkivu) i potvrđena je uspešna inkorporacija gentamicina u prevlaku, što ovu kompozitnu prevlaku čini pogodnom za potencijalnu primenu u biomedicini.

Površine titanskih implantata se mogu unaprediti primenom biokeramičkih, multifunkcionalnih prevlaka koristeći proces elektroforetskog taloženja (EPD) u cilju sprečavanja korozije, poboljšanja biokompatibilnosti i antibakterijske aktivnosti, kao i unapređenja osteointegracije. Materijali poput hidroksiapatita (HAP), hitozana (CS), poli(vinil-alkohola) (PVA) i antibiotika gentamicina (Gent) su korišćeni u ovom procesu kako bi se razvile poboljšane antibakterijske kompozitne prevlake. Nakon taloženja, prevlake su potapane u simuliranu telesnu tečnost (SBF) na 37 °C, a zatim je izvršena karakterizacija skenirajućom elektronskom mikroskopijom sa emisijom polja (FE-SEM) i rendgenskom difrakcionom analizom (XRD). Bioaktivnost istaloženih prevlaka je pokazana i analizom aktivnosti alkalne fosfataze prema MRC-5 i L929 ćelijskim linijama. Koncentracija otpuštenog gentamicina je određena korišćenjem tečne hromatografije visokih performansi (HPLC) sa masenom detekcijom (MS).

Hidrogel poli(vinil alkohol)/hitozan/gentamicin (PVA/CHI/Gent) pripremljen je fizičkim umrežavanjem disperzije poli(vinil alkohola)/hitozana i namenjen je za upotrebu kao materijal za medicinske obloge dubokih nekrotičnih rana kao što su dekubitusi. Ispitivane su fizičko-hemijske (FTIR, SEM), mehaničke i biološke (citotoksičnost, antibakterijska aktivnost) osobine. Mehanizam difuzije gentamicina iz hidrogela PVA/CHI/Gent proučavan je upoređivanjem novog dvo-kompartmentskog modela sa opštim frakcionim izvodima (GFD) i Korsmajer-Pepas, Makoid-Banakar i Kopča difuzionih modela. GFD model bolje se poklapao sa eksperimentalnim podacima od drugih modela i takođe je omogućio određivanje koeficijenta difuzije gentamicina tokom celog proučavanog vremenskog perioda.

Biocomposite hydroxyapatite/poly(vinyl alcohol)/chitosan/gentamicin coatings were fabricated on titanium by an electrophoretic deposition process (EPD) from an aqueous suspension using the constant voltage method. Characterization of the deposited coatings was performed by scanning electron micros-copy with field emission (FE-SEM), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD) after immersion in simulated body fluid (SBF) at 37 °C. The concentration of the released gentamicin was determined using high-performance liquid chromatography (HPLC) coupled with a mass spectrometer (MS). The release profile confirmed an initial “burst-release effect” with ~ 30 % of the gen-tamicin released in the first 48 h, which could be of assistance in the prevention of biofilm formation. An-tibacterial activity was proven by the agar diffusion method on Staphylococcus aureus TL and Escherich-ia coli ATCC 25922 bacterial strains. Cytotoxicity was tested by the dye exclusion test (DET) on MRC-5 and L929 fibroblast cell lines, with both coatings expressing nontoxicity. The results showed the high ap-plicability potential of a poly(vinyl alcohol)-based biocomposite coating for medical purposes.

Kompozitna prevlaka hidroksiapatita (HAP) sa prirodnim polimerima hitozanom (CS) i polivinil-alkoholom (PVA), kao i sa antibiotikom gentamicinom (Gent) je elektroforetski taložena na titanu, pri konstantnom naponu. Formiranje nove kompozitne HAP/PVA/CS/Gent prevlake je potvrđeno infracrvenom spektroskopijom sa Furijeovom transformacijom. Necitotoksični efekat istaložene HAP/PVA/CS/Gent prevlake je dokazan MTT testom prema dve ćelijske linije (MRC-5 i L929). Sposobnost HAP/PVA/CS/Gent prevlake da indukuje i promoviše osteointegraciju je pokazana ALP testom., Composite coating of hydroxyapatite (HAP) with natural polymers chitosan (CS) and poly(vinyl alcohol) (PVA) with the antibiotic gentamicin (Gent) was electrophoretically deposited on titanium from an aqueous suspension, at a constant voltage. Formation of a new composite HAP/PVA/CS/Gent coating was confirmed by Fourier transform infrared spectroscopy. Non-cytotoxicity of deposited HAP/PVA/CS/Gent coating was demonstrated by MTT assay towards two types of cell lines (MRC-5 and L929). HAP/PVA/CS/Gent coating ability to induce and promote the osseointegration process was proved by the ALP assay.

Electrophoretic deposition (EPD) was employed to fabricate composite coatings aimed for orthopedic implants. Hydroxyapatite (HAP), poly(vinyl alcohol) (PVA) and chitosan (CS) coatings, with or without antibiotic gentamicin (Gent) were deposited in a single-step process from aqueous suspension, using EPD. Polymer/mineral composite coatings were formed with the aim to mimic the natural composition of bone tissue, along with improved coatings antibacterial properties, at the same time serving as a drug carrier, allowing local administration of antibiotic. Structural and morphological characterization of HAP/PVA/CS and HAP/PVA/CS/Gent coatings was investigated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG/DTG), and scanning electron microscopy (SEM) proving carbonate-substituted HAP. The presence of gentamicin contributed to the bactericidal activity of composite HAP/PVA/CS/Gent coating against Staphylococcus aureus and Escherichia coli. Cytotoxicity studies were performed towards human MRC-5 and mice L929 fibroblast cell lines, and both investigated samples (HAP/PVA/CS and HAP/PVA/CS/Gent) expressed good biocompatibility, without causing toxic effect on tested cells. Biomineralization potential was investigated by measuring the alkaline phosphatase activity, demonstrating high potential of HAP/PVA/CS/Gent to induce the growth of new HAP layer. Therefore, the present investigation proposes the production of nents, along with antibiotic gentamicin, improving the antibacterial coatings’ properties.

Uvođenje antibiotika u polimer/mineralnu kompozitnu prevlaku poboljšava antibakterijska svojstva prevlaka. Kompozitna prevlaka (hidroksiapatit - HAP, poli(vinilalkohol), hitozan, gentamicin) dobijena je elektroforetskim taloženjem iz četvorokomponentne vodene suspenzije. Primenom termogravimetrijske i rendgenske difrakcione analize pokazano je prisustvo karbonatno-supstituisanog HAP. Antibakterijska aktivnost kompozitne prevlake sa gentamicinom potvrđena je protiv soja S. aureus i E. coli, čineći ovu prevlaku pogodnom za potencijalnu primenu u biomedicini., Antibiotic introduction in polymer/mineral coating can improve the antibacterial properties of coatings. Composite coating (hydroxyapatite, poly(vinyl alcohol), chitosan, gentamicin) was fabricated from a four-component aqueous suspension using electrophoretic deposition. Structural and morphological characterization of the coating was investigated by X-ray diffraction and thermogravimetric analysis proving carbonate-substituted HAP. The presence of gentamicin contributed to the antibacterial activity of composite coating against S. aureus and E. coli strains, representing a suitable material for possible application in biomedicine.

Medical implants have improved the quality of life of many patients. However, surgical intervention may eventually lead to implant microbial contamination. The aims of this research were to develop an easy, robust, quantitative assay to assess surface antimicrobial activities, especially the anti-nascent biofilm activity, and to identify control surfaces, allowing for international comparisons. Using new antimicrobial assays to assess the inhibition of nascent biofilm during persistent contact or after transient contact with bacteria, we show that the 5 cent Euro coin or other metal-based antibacterial coins can be used as positive controls, as more than 4 log reduction on bacterial survival was observed when using either S. aureus or P. aeruginosa as targets. The methods and controls described here could be useful to develop an easy, flexible and standardizable assay to assess relevant antimicrobial activities of new implant materials developed by industries and academics., SCOPUS: ar.j, info:eu-repo/semantics/published