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Cilj ove doktorske disertacije bila je sinteza novih biomaterijala, hidrogelova polivinil-alkohola i hitozana, sa i bez grafena, sa elektrohemijski inkorporisanim nanočesticama srebra i njihova detaljna karakterizacija u cilju ispitivanja mogućnosti primene u obliku antibakterijskih obloga za rane. Hidrogelovi srebro/polivinil-alkohol/hitozan i srebro/polivinil-alkohol/hitozan/grafen su dobijeni metodom zamrzavanja i odmrzavanja, praćenom elektrohemijskom in situ sintezom nanočestica srebra unutar polimernih matrica hidrogelova, nakon bubrenja u rastvoru Ag+ jona. Detaljna karakterizacija dobijenih hidrogelova je izvršena u cilju ispitivanja njihove strukture, morfologije, hemijskog sastava, mehaničkih i termičkih svojstava, kao i oblika, dimenzija i strukture sintetisanih nanočestica srebra. Ispitan je uticaj sadržaja hitozana na efikasnost elektrohemijske sinteze nanočestica, kao i na strukturu i svojstva samih hidrogelova. Karakterizacija u in vitro uslovima je obuhvatala ispitivanje sposobnosti bubrenja svih dobijenih hidrogelova i kinetike otpuštanja srebra u fiziološki relevantnim uslovima (pH 7,4, 37 ºC), kao i određivanje antibakterijskih svojstava i biokompatibilnosti dobijenih materijala. Rezultati ove disertacije su pokazali da dobijeni nanokompozitni hidrogelovi imaju visok potencijal za primenu kao aktivne obloge za rane sa jakim antibakterijskim efektom, koji se postiže kontrolisanim otpuštanjem elektrohemijski sintetisanih nanočestica srebra. Dobijeni rezultati su takođe pokazali povoljan efekat hitozana, kako na samu elektrohemijsku sintezu nanočestica srebra, tako i na fizičko-hemijska i antibakterijska svojstva dobijenih hidrogelova, tako da se ovi materijali mogu smatrati pogodnim kandidatima za dalja ispitivanja u oblasti biomedicinskih materijala. Ključne The aim of this doctoral dissertation was the synthesis of new biomaterials, poly(vinyl alcohol) and chitosan hydrogels, with and without graphene, with electrochemically incorporated silver nanoparticles, and their detailed characterization in terms of potential applications as antibacterial wound dressing materials. Silver/poly(vinyl alcohol)/chitosan and silver/poly(vinyl alcohol)/chitosan/graphene hydrogels were obtained via the freezing-thawing method, followed by in situ electrochemical synthesis of silver nanoparticles inside hydrogel matrices, previously swollen in Ag+ ion solutions. Extensive characterization of the obtained hydrogels was carried out in order to examine their structure, morphology, chemical composition, mechanical and thermal properties, as well as the shape, size and structure of the synthesized silver nanoparticles. The effect of chitosan content on the electrochemical synthesis yield and on the structure and properties of the synthesized hydrogels was also investigated. In vitro characterizations included the investigation of the hydrogels’ swelling properties and silver release kinetics in physiologically-relevant environment (pH 7.4, 37 ºC), as well as the determination of antibacterial properties and biocompatibility. The results of this dissertation demonstrated that the synthesized nanocomposite hydrogels exhibited compelling potential for applications as active wound dressings with potent antibacterial effect, achieved through controlled release of the electrochemically embedded silver nanoparticles. The significant beneficial chitosan influence on both the electrochemical synthesis of silver nanoparticles, and the physicochemical and antibacterial properties of the hydrogels was proven. Therefore, these materials could be considered as apt candidates for further research in biomedical materials field.

Ova doktorska disertacija dizajnirana je u cilju da se ispita biokompatibilnost dva novosintetisana i prethodno in vitro okarakterisana hidrogela na bazi sintetskog polimera polivinil-alkohola − Ag/PVA i Ag/PVA/Gr, koji su namenjeni za izradu obloga za rane ili za implantate za meka tkiva. Polivinil-alkohol (PVA) je sintetički polimer koji se često koristi u biomedicini zbog svoje netoksičnosti, rastvorljivosti, biokompatibilnosti, elastičnosti i sposobnosti stvaranja reverzibilnih hidrogelova s visokom sposobnošću sorpcije. U poslednjih nekoliko godina, istraživanja se takođe fokusiraju na ugradnju grafena (Gr) u hidrogelove PVA kako bi se poboljšala njihova mehanička čvrstoća i trajnost. U inženjerstvu tkiva i regenerativnoj medicini posebno je važno da implantati i zavoji sadrže antiinflamatornu i antibakterijsku aktivnu komponentu kako bi zaštitili sterilnost rane ili sprečili infekciju u tkivu koje okružuje implantat. Poznato je da nanočestice srebra (eng. silver nanoparticles, AgNPs) poseduju odličnu antibakterijsku aktivnost, pa se zbog toga često koriste kao aktivna komponenta biomaterijala na bazi hidrogela od PVA. U cilju ispitivanja biokompatibilnosti novosintetisanih hidrogelova, praćena je reakcija mekog tkiva na duboko potkožno postavljene implantate od Ag/PVA i Ag/PVA/Gr i poređena je sa reakcijom na komercijalnu oblogu za rane na bazi kalcijum-alginata (Suprasorb©, Lohmann & Rauscher GmbH & Co. KG, Neuwied, Germany), koja je implantirana na identičan način. Procenjivan je tkivni iritacioni indeks (IrI) kao osnovna mera tkivnog odgovora na implantirane hidrogelove. Za određivanje stepena biokompatibilnosti merena je debljina vezivnotkivne kapsule oko implantiranih hidrogelova, broj inflamatornih ćelija, uključujući i Langerhansove džinovske ćelije, broj makrofaga u periimplantnoj zoni i njihova enevntualna migracija u biomaterijal, kao i brojnost krvnih sudova mikrovaskularnog korita oko zone implantacije. Posmatran je odnos proliferacije i apoptoze ćelijskih entiteta kože i potkožnog tkiva odgovornih za procese regeneracije i reparacije... This doctoral dissertation was designed in order to test the biocompatibility of two newly synthesized and previously in vitro characterized hydrogels based on poly(vinyl alcohol) polymers - Ag/PVA and Ag/PVA/Gr, which are intended for making wound dressings or soft tissue implants tissue. Poly(vinyl alcohol) (PVA) is a synthetic polymer commonly used in biomedicine due to its non-toxicity, solubility, biocompatibility, elasticity and the ability to produce reversible hydrogels with high sorption capacity. In the last few years, research has also focused on the incorporation of graphene (Gr) into hydrogel PVAs, in order to improve their mechanical strength and durability. In tissue engineering and regenerative medicine, it is particularly important that implants and bandages contain an antiinflammatory and antibacterial active ingredient to protect the sterility of the wound, or to prevent infection in the implant surrounding tissue. It is known that silver nanoparticles (AgNPs) have excellent antibacterial activity and are therefore often used as an active component of PVA-based hydrogel biomaterials. In order to test the biocompatibility of newly synthesized hydrogels, the soft tissue response to deep subcutaneously implanted Ag/PVA and Ag/PVA/Gr implants was compared to the reaction to the commercial calcium-alginate wound pad (Suprasorb ©, Lohmann & Rauscher GmbH & Co. KG, Neuwied, Germany), which is implanted in an identical manner. The tissue irritation index (IrI) was evaluated as the basic measure of tissue response to implanted hydrogels. In order to determine the degree of biocompatibility, the thickness of the connective tissue capsule around the implanted hydrogels, the number of inflammatory cells, including the Langerhans giant cells, the number of macrophages in the perimplant zone and their eneventual migration to the biomaterial, as well as the number of blood vessels around the implantation zone, were measured. The ratio of proliferating and apoptotic cellular skin and subcutaneous tissue cellular entities was observed, due to their responsibility for regeneration and reparation processes...

This doctoral dissertation was designed in order to test the biocompatibility of two newly synthesized and previously in vitro characterized hydrogels based on poly(vinyl alcohol) polymers - Ag/PVA and Ag/PVA/Gr, which are intended for making wound dressings or soft tissue implants tissue. Poly(vinyl alcohol) (PVA) is a synthetic polymer commonly used in biomedicine due to its non-toxicity, solubility, biocompatibility, elasticity and the ability to produce reversible hydrogels with high sorption capacity. In the last few years, research has also focused on the incorporation of graphene (Gr) into hydrogel PVAs, in order to improve their mechanical strength and durability. In tissue engineering and regenerative medicine, it is particularly important that implants and bandages contain an antiinflammatory and antibacterial active ingredient to protect the sterility of the wound, or to prevent infection in the implant surrounding tissue. It is known that silver nanoparticles (AgNPs) have excellent antibacterial activity and are therefore often used as an active component of PVA-based hydrogel biomaterials. In order to test the biocompatibility of newly synthesized hydrogels, the soft tissue response to deep subcutaneously implanted Ag/PVA and Ag/PVA/Gr implants was compared to the reaction to the commercial calcium-alginate wound pad (Suprasorb ©, Lohmann & Rauscher GmbH & Co. KG, Neuwied, Germany), which is implanted in an identical manner. The tissue irritation index (IrI) was evaluated as the basic measure of tissue response to implanted hydrogels. In order to determine the degree of biocompatibility, the thickness of the connective tissue capsule around the implanted hydrogels, the number of inflammatory cells, including the Langerhans giant cells, the number of macrophages in the perimplant zone and their eneventual migration to the biomaterial, as well as the number of blood vessels around the implantation zone, were measured. The ratio of proliferating and apoptotic cellular skin and subcutaneous tissue cellular entities was observed, due to their responsibility for regeneration and reparation processes... Ova doktorska disertacija dizajnirana je u cilju da se ispita biokompatibilnost dva novosintetisana i prethodno in vitro okarakterisana hidrogela na bazi sintetskog polimera polivinil-alkohola − Ag/PVA i Ag/PVA/Gr, koji su namenjeni za izradu obloga za rane ili za implantate za meka tkiva. Polivinil-alkohol (PVA) je sintetički polimer koji se često koristi u biomedicini zbog svoje netoksičnosti, rastvorljivosti, biokompatibilnosti, elastičnosti i sposobnosti stvaranja reverzibilnih hidrogelova s visokom sposobnošću sorpcije. U poslednjih nekoliko godina, istraživanja se takođe fokusiraju na ugradnju grafena (Gr) u hidrogelove PVA kako bi se poboljšala njihova mehanička čvrstoća i trajnost. U inženjerstvu tkiva i regenerativnoj medicini posebno je važno da implantati i zavoji sadrže antiinflamatornu i antibakterijsku aktivnu komponentu kako bi zaštitili sterilnost rane ili sprečili infekciju u tkivu koje okružuje implantat. Poznato je da nanočestice srebra (eng. silver nanoparticles, AgNPs) poseduju odličnu antibakterijsku aktivnost, pa se zbog toga često koriste kao aktivna komponenta biomaterijala na bazi hidrogela od PVA. U cilju ispitivanja biokompatibilnosti novosintetisanih hidrogelova, praćena je reakcija mekog tkiva na duboko potkožno postavljene implantate od Ag/PVA i Ag/PVA/Gr i poređena je sa reakcijom na komercijalnu oblogu za rane na bazi kalcijum-alginata (Suprasorb©, Lohmann & Rauscher GmbH & Co. KG, Neuwied, Germany), koja je implantirana na identičan način. Procenjivan je tkivni iritacioni indeks (IrI) kao osnovna mera tkivnog odgovora na implantirane hidrogelove. Za određivanje stepena biokompatibilnosti merena je debljina vezivnotkivne kapsule oko implantiranih hidrogelova, broj inflamatornih ćelija, uključujući i Langerhansove džinovske ćelije, broj makrofaga u periimplantnoj zoni i njihova enevntualna migracija u biomaterijal, kao i brojnost krvnih sudova mikrovaskularnog korita oko zone implantacije. Posmatran je odnos proliferacije i apoptoze ćelijskih entiteta kože i potkožnog tkiva odgovornih za procese regeneracije i reparacije...

Cilj ove doktorske disertacije je dobijanje srebro/polivinil-alkohol (Ag/PVA) i srebro/polivinil-alkohol/grafen (Ag/PVA/Gr) nanokompozita elektrohemijskom sintezom nanočestica srebra u PVA rastvoru, odnosno PVA/Gr koloidnoj disperziji. Elektrohemijska reakcija izvodi se pri galvanostatskim uslovima, pri čemu je količinu, oblik i veličinu nanočestica srebra (AgNPs) moguće kontrolisati izborom vrednosti gustine struje i vremena sinteze, te je međusobna zavisnost ovih parametara detaljno ispitana u ovom radu. Svojstva nanokompozita dobijenih u vidu koloidnih disperzija, filmova i hidrogelova ispitane su u cilju potencijalne biomedicinske primene... The goal of this doctoral dissertation is to obtain silver/poly(vinyl alcohol) (Ag/PVA) and silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) nanocomposites by electrochemical synthesis of silver nanoparticles (AgNPs) in the PVA solution, or PVA/Gr colloidal dispersion. The electrochemical reaction is performed under galvanostatic conditions, whereby the quantity, shape and size of the silver nanoparticles can be controlled by selecting the value of the current density and the time of the synthesis, and the relation between these parameters is thoroughly examined in this paper. The properties of the nanocomposites obtained in the form of colloidal dispersions, films and hydrogels were examined for potential biomedical application...

In this doctoral dissertation, a composite hydrogel consisting of poly(vinyl alcohol), graphene and silver nanoparticles, (Ag/PVA/Gr), was prepared by the immobilization of silver nanoparticles (AgNPs) in poly(vinyl alcohol)/graphene (PVA/Gr) hydrogel matrix in two steps. The first step was cross linking of the PVA/Gr colloid solution by the freezing/thawing method, while in the second step, in situ electrochemical method was used to incorporate AgNPs inside the PVA/Gr hydrogel matrix. The main aim of this study was to produce the nanocomposite graphene-based biomaterial with incorporated silver nanoparticles using in situ electrochemical method, aimed for soft tissue implants, wound dressings and drug delivery. The electrochemical route of nanoparticles synthesis is especially attractive for biomedical applications due to high purity and precise size control of metal particles and the absence of chemical cross linking agents and undesired products. Repeated cyclic freezing/thawing method was used to prepare poly(vinyl alcohol) PVA and poly(vinyl alcohol)/graphene (PVA/Gr) hydrogel discs, followed by electrochemical reduction method of different concentrations of Ag+ ions (0.25, 0.5,1.0 and 3.9 mM AgNO3 swelling solution) inside the hydrogel polymer matrices at a constant voltage that enables the silver particle size control, in a specially designed electrochemical cell. Silver/poly(vinyl alcohol) (Ag/PVA) and silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) nanocomposites were characterized by UV–visible spectroscopy. The absorption spectra at about 405-420 nm proved existence of AgNPs in both Ag/PVA and Ag/PVA/Gr nanocomposites. Cyclic voltammetry revealed some oxidation and reduction peaks suggesting the presence of AgNPs between polymer chains. Raman spectroscopy analysis confirmed the graphene structure in its pure form, X-ray diffraction was used to reveal the additional interactions established between the PVA molecules and graphene sheets and the AgNPs situated between the polymer chains in viii the Ag/PVA/Gr nanocomposite. The calculated interspacing (d-spacing) value for (002) lattice plane of the PVA and Ag/PVA hydrogels was 0.457 nm, while the obtained value changed slightly with the introduction of graphene sheets (0.449 nm for Ag/PVA/Gr nanocomposite). Fourier transform infrared spectroscopy (FTIR) results for both Ag/PVA and Ag/PVA/Gr nanocomposites suggested the interaction between AgNPs and hydroxyl groups of the PVA molecules through decoupling between the corresponding vibrations. Thermogravimetric analysis and corresponding differential thermal analysis were done to investigate the role of graphene sheets in the thermal stability of thus prepared nanocomposite samples, and the results showed higher stability of Ag/PVA/Gr than Ag/PVA nanocomposites. Morphology of the prepared PVA, PVA/Gr, Ag/PVA and Ag/PVA/Gr samples were examined by field-emission scanning electron microscopy (FE-SEM) technique and the microphotographs showed sphere-shaped AgNPs at nanoscale levels which were around 36 nm in the Ag/PVA and around 17 nm in the Ag/PVA/Gr nanocomposites... Ova doktorska disertacija se bavi sintezom hidrogelova polivinil-alkohola, grafena i nanočestica srebra (Ag/PVA/Gr), imobilizacijom nanočestica srebra u matrici hidrogela polivinil-alkohol/grafen (PVA/Gr) u dva koraka. Prvi korak je umrežavanje koloidnog rastvora PVA/Gr metodom zamrzavanja i odmrzavanja, dok je u drugom koraku primenjena in situ elektrohemijska metoda za inkorporaciju nanočestica srebra u matrici PVA/Gr hidrogela. Glavni cilj ovog istraživanja je bila priprema nanokompozitnih biomaterijala na bazi grafena sa inkorporisanim nanočesticama srebra, sa mogućom primenom u vidu implantata mekog tkiva, obloga za rane i nosača za lekove. Elektrohemijski postupak sinteze nanočestica je posebno atraktivan za primene u biomedicini, zbog velike čistoće i mogućnosti precizne kontrole dobijenih nanočestica, kao i zbog odsustva hemijskih agenasa i neželjenih produkata. Metoda umrežavanja cikličnim zamrzavanjem i odmrzavanjem je korišćena u cilju dobijanja polivinil-alkohol (PVA) i polivinil-alkohol/grafen (PVA/Gr) hidrogelova u obliku diskova, a zatim je izvršena elektrohemijska redukcija Ag+ jona različitih koncentracija (0,25, 0,5,1,0 i 3,9 mM AgNO3 swelling solution) u polimernoj matrici hidrogela, na konstantnom naponu, što omogućava kontrolu dimenzija čestica srebra, u posebno dizajniranoj elektrohemijskoj ćeliji. Srebro/polivinil-alkohol (Ag/PVA) i srebro/polivinil-alkohol/grafen (Ag/PVA/Gr) nanokompoziti su karakterisani UV-vidljivom spektroskopijom. Apsorpcioni spektri sa maksimumom na oko 405-420 nm su dokazali prisustvo nanočestica srebra u Ag/PVA i Ag/PVA/Gr nanokompozitima. Cikličnom voltametrijom su pokazani pikovi oksidacije i redukcije koji ukazuju na prisustvo nanočestica srebra u polimernoj matrici. Ramanova spektroskopija je potvrdila čistu grafensku strukturu, dok je rendgenska difrakcija korišćena za ispitivanje interakcija između PVA molekula sa grafenom i nanočesticama srebra, smeštenim između polimernih lanaca Ag/PVA/Gr nanokompozita. Izračunato rastojanje između krisalnih xi ravni za (002) ravan u PVA i Ag/PVA hidrogelovima je iznosilo 0.457 nm, dok se ova vrednost promenila nakon inkorporacije grafena (0.449 nm za Ag/PVA/Gr nanokompozit). Rezultati analize infracrvenom spektroskopijom sa Furijeovom transformacijom (FTIR) za Ag/PVA i Ag/PVA/Gr nanokompozite su ukazali na interakcije između nanočestica srebra i hidroksilnih grupa na PVA molekulima, na osnovu razdvajanja odgovarajućih vibracionih traka. Termogravimetrijska analiza i diferencijalna termogravimetrijska analiza su korišćene radi ispitivanja termičke stabilnosti dobijenih uzoraka hidrogelova, a rezultati su pokazali povećanu stabilnost Ag/PVA/Gr u odnosu na Ag/PVA nanokompozite. Morfologija dobijenih uzoraka PVA, PVA/Gr, Ag/PVA i Ag/PVA/Gr je ispitana tehnikom skenirajuće elektronske mikroskopije (FE-SEM), a na mikrografijama su uočene čestice srebra sfernog oblika i nanometarskih dimenzija oko 36 nm u Ag/PVA i oko 17 nm u Ag/PVA/Gr nanokompozitu...

Ukrasni okvir slike Poklonstvo pastira iz Vranjica (Solin) restauriran je 2009. godine u Hrvatskom restauratorskom zavodu – Restauratorskom odjelu Split. Nakon istražnih radova, uzimajući u obzir neprimjerene uvjete u kojima se umjetnina dugo nalazila, odlučeno je da se upotrijebe materijali otporniji na oscilaciju vlage i temperature od onih prirodnog podrijetla. Polivinil-alkohol Mowiol 4–8 (netradicionalni materijal za kitiranje i preparaciju), koji je komplementaran s originalnim materijalima, odabran je i zbog svojstva dugotrajne reverzibilnosti. Ovim je radom izložen kratak pregled konzervatorsko-restauratorskih radova na ukrasnom okviru, a ujedno je i revidirana analiza Mowiola 4–88 kao restauratorskog materijala., The goal of this research was to encourage conservators and restorers to re-evaluate traditional fillings, of which only a small number meet the criteria of ageing characteristics, including reversibility, preservation of flexibility, colour stability, and resistance to mould and rot. The research was a result of the practical need to preserve a decorative gilded and polychrome frame from the parish church in Vranjic (17th c.?) and to provide substantiated scientific data on the basis of which polyvinyl alcohol would become a fully accepted alternative substance for use as a binding ingredient in fillings and chalk bases. Another goal of the research was to emphasize the need to sort decorative frames, since high-quality frames of this kind are a much-appreciated element of our heritage and, after completion of the research, they could be published. The frame a tortiglione, with rhythmical alteration of black and gilded surfaces, resembles the decorative frames of the Lombard region which appeared in the second half of the 16th c. The primary goal of the conservation-restoration intervention was to preserve the artefact’s integrity by presenting the well-preserved original layer of the black polychromy and water gilding. The exploration suggested that it would be difficult to remove two layers of paint, so an alternative system for paint removal was devised, similar to the so-called Pettenkofer’s method for softening the paint film by using vapour as a solvent. The second goal was to use reversible materials whose characteristics would be better than those of organic materials. Extensive research based on an analysis of the condition of the frame material confirmed that it would be better to use polyvinyl alcohol, manufactured under the name ‘Mowiol 4–88’, for filling and preparing the chalk base. Mowiol’s physical and chemical features are presented in detail, to facilitate the reader’s understanding of the decision. The third and final goal of the research was to meet the formal requirement of integrating the decorative frame and the painting Adoration of the Shepherds, which was much better preserved.

Worldwide, there is u currently considerable care for the development of biodegradable microspheres as systems for controlled release of medicaments. The major disadvantage of traditional administration routes of medicaments is the need for frequent repetition. Encapsulation has been proven to be an effective vehicle for the controlled delivery of various medicaments. The encapsulation efficiency and release kinetics of the medicaments have been found to be dependent upon the size of the microspheres synthesized. The aim of this study was to formulate microparticles from poly-dl-lactide (PDLLA) by modified precipitation method. Bovine serum albumin (BSA) was used as a model protein for encapsulation. The surfactant polyvinyl alcohol (PVA) was incorporated to increase encapsulation efficiency and to achieve PDLLA spheres with desired size. The main focus was to study the effect of co-solvent selection (methanol or ethanol), PVA concentration, chloroform-to-water ratio, the speed and time of homogenization and solvent removal rate on the properties of microparticles. The average size and morphology of microparticles varied substantially among these preparation conditions. An increase in stirring rate and time of homogenization and concentration of stabilizer agent were found to reduce moderately the size of microparticles. Other process parameters had limited influence on particle size.