Synthesis of polymer nanomaterials by the electrospinning method and application in the field of tissue engineering

[K. D. Virijević]

148 str.

Istraživanje sprovedeno za potrebe izrade ove disertacije je imalo za cilj dobijanje polimernih nanovlakna pomoću elektrospining tehnologije, sa ciljem razvoja naprednih materijala za primenu u biomedicinskom polju. Ispitivane klase polimera u okviru ovog istraživanja su uključivale sintetičke polimere, kao što su poli(εkaprolakton) (PCL), polietilen glikol (PEG), i prirodne biološki aktivne polimere, kao što su proteini (želatin) i polisaharidi (hitozan). Osnovni cilj istraživanja se bazirao na optimizaciji hemijskog sastava polimernih rastvora kako bi se dobila nanovlakna (skefoldi) pogodna za primenu u tretmanima ubrzanog zarastanja rana. Uslovi eksperimenta su bili kontrolisani i praćeni kako bi se uočila njihova promena na uticaj parametara dobijenih nanovlakana. Nakon toga, prikupljeni podaci su upotrebljeni za obuku modela neuronske mreže, sa ciljem definisanja optimalnih uslova za dobijanje željenih karakteristika nanovlakana. Nanovlakna dobijena iz svih testiranih klasa polimera analizirana su kroz in vitro i in vivo metode. Kao dodatan korak, nanovlakna su bila impregnirana komercijalnim antibiotskim agensima, kao što su ciprofloksacin hidrohlorid i gentamicin sulfat, radi poboljšanja terapeutskih svojstava materijala za primene u regeneraciji kože. Karakterizacija nanovlakana je izvršena korišćenjem različitih tehnika, uključujući skenirajuću elektronsku mikroskopiju (SEM), energetsku disperzivnu spektroskopiju (SEM/EDS), mikroskopiju atomskih sila (AFM) i infracrvenu spektroskopiju Furijeove transformacije (FTIR), da bi se procenila morfologija, struktura i tekstura vlakna. In vitro testovi su uključivali toksikološke i mikrobiološke analize, merenja apsorpcije vode i degradacije u fiziološkim uslovima, dok in vivo testovi su bili primenjeni na modelima pacova i kokošijih jaja za procenu biokompatibilnosti, regenerativnih i neoangiogenih svojstava. Rezultati su pokazali da sintetisana nanovlakna poseduju osobine biokompatibilnosti, značajnu antibakterijsku aktivnost prema ispitivanim patogenima, kao i sposobnost da ubrzaju zarastanje rana i regeneraciju tkiva uz sprečavanje infekcija. Dobijene karakteristike ukazuju na značajan potencijal sintetisanih nanovlakana za razvoj inovativnih materijala sa primenom u tkivnom inženjeringu. U izradu ove doktorske disertacije bile su uključene i institucije: Institut za virusologiju, vakcine i serume „Torlak”, Beograd; Institut za molekularnu genetiku i genetičko inženjerstvo, Beograd; Institut za nuklearne nauke „Vinča”, Beograd; Tehnološko-metalurški fakultet Univerziteta u Beogradu; Institut za lake konstrukcije i strukturnu biomehaniku, Tehnički univerzitet u Beču, Austrija; Fakultet medicinskih nauka Univerziteta u Kragujevcu; Prirodno-matematički fakultet Univerziteta u Kragujevcu;.

The research conducted for this dissertation aimed to obtain polymer nanofibers using electrospinning technology, aiming to develop advanced materials for biomedical applications. The polymer classes examined in this research included synthetic polymers, such as poly(εcaprolactone) (PCL), polyethylene glycol (PEG), and natural biologically active polymers, such as proteins (gelatin) and carbohydrates (chitosan). The main goal of the research was to optimize the chemical composition of polymer solutions in order to obtain nanofibers (scaffolds) suitable for use in accelerated wound healing treatments. The experimental conditions were controlled and monitored to observe their influence on the parameters of the obtained nanofibers. After that, the data were collected and used to train a neural network model to set the experimental conditions further to obtain the desired characteristics of the nanofibers. Nanofibers obtained from all tested polymer classes were analyzed through in vitro and in vivo methods. As an additional step, the nanofibers were impregnated with commercial antibiotic agents, such as ciprofloxacin hydrochloride and gentamicin sulfate, to improve the therapeutic properties of the materials for applications in skin regeneration. Characterization of the nanofibers was performed using various techniques, including scanning electron microscopy (SEM), energy dispersive spectroscopy (SEM/EDS), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR), to evaluate the morphology, structure, and texture of the nanofibers. In vitro tests included toxicological and microbiological analyses, water absorption and degradation measurements under physiological conditions, as well as in vivo tests in rat and egg models to assess biocompatibility, regenerative, and neoangiogenic properties. The results showed that the synthesized nanofibers possess biocompatibility properties, significant antibacterial activity against the tested pathogens, as well as the ability to accelerate wound healing and tissue regeneration while preventing infections. These characteristics indicate the high potential of synthesized nanofibers for the development of innovative materials with applications in tissue engineering. The following institutions were also involved in the development of this doctoral dissertation: the Institute of Virology, Vaccines and Sera "Torlak", Belgrade; the Institute of Molecular Genetics and Genetic Engineering, Belgrade; the Vinča Institute of Nuclear Sciences, Belgrade; the Faculty of Technology and Metallurgy, University of Belgrade; the Institute of Lightweight Design and Structural Biomechanics, Vienna University of Technology, Austria; the Faculty of Medical Sciences, University of Kragujevac; and the Faculty of Science, University of Kragujevac.

nanovlakna, polimeri, tkivni inženjering, veštačka inteligencija, zarastanje rana

nanofibers, polymers, tissue engineering, artificial intelligence, wound healing

615.47:004.8(043.3) 004.8

Biomedicinska tehnika, veštačka inteligencija

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