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Antibiotic resistance isone of the biggest threats to global health, food securityand development today[1].However, development of conventional anti-infective drugs is going slowly, so new innovative strategies and more research are urgently needed in identifying, developing, implementing and evaluating novel therapies for antibiotic-resistant infections.The two-year ProHealingAC project, funded by the Science Fundof theRepublicof Serbia, aims to use beneficial properties of ACand probiotic microorganisms in developing anew strategy for prevention and localtreatment of antibiotic-resistant infections in wounds. Previously, it has been shown that activated charcoal (AC) in conjunction with different active agents has an efficient antimicrobial activity [2,3]. The aimof this projectis to develop biocomposites (BCs) based on AC fabric, as adsorptive component, and probiotics, as bioactive component in order to achieve their synergetic activity forefficient and sustained localdelivery of bioactive agents directly into the woundarea.Also, special attention has been given to the influence of glucose level (normo-and hyperglycemia) in the microenvironment of the wound.

Traditional cotton wound dressings, like gauze and bandages, remain popular in wound care due to their affordability. However, they have drawbacks: adhering to wounds, risking tissue damage and low absorbance of secretions, requiring multiple layers, and causing discomfort. Modern alternatives, such as alginate hydrogel dressings, target these issues. Designed for moderate to intense exudate wounds, they enhance comfort and treatment effectiveness. Yet, their higher cost limits accessibility. Moreover, neither alginate nor cotton gauze offer bioactivity, while mechanical strength of alginate hydrogel may be inadequate. This work aims to develop enhanced gauzes to overcome these challenges, offering improved functionality at affordable costs and superior wound care.

Tehničko rešenje obuhvata formulaciju i tehnologiju dobijanja unapređenih gaza za tretman rana koje su porozne, ojačane tkaninom i ne lepe se za ranu, pri tome upijaju sekret rane i regulišu njenu vlažnost, dok kontrolisano mogu da otpuštaju različite aktivne komponente, kao što su npr. joni srebra ili cinka. Prema tome, tehničko rešenje pripada oblasti materijali i hemijske tehnologije.

Composites based on Zn-alginate hydrogels in the form of beads were produced by extrusion of a suspension containing 0.5 % w/w of alginate and 20 % w/w of activated charcoal (AC) with the intent to simultaneously release two active agents, Zn2+ and AC particles, in a physiological-like environment. The obtained composite beads were analyzed by FE-SEM and characterized regarding textural parameters, as well as Zn2+ and AC release kinetics in the physiological saline solution. Zn(2+)ions were quickly released reaching the equilibrium concentration within the first hour in the contrary to the release of AC particles, which was described by internal diffusion with the apparent diffusion coefficient of approximately 10(-13) m(2) s(-1). Potential functionality of the obtained beads was evaluated regarding antibacterial activity in suspensions of the standard bacterial strain Escherichia coli 25922. The observed strong bactericidal effects were related to the quick release of Zn2+ that was not affected by AC. Thus, taking into account results of this study, as well as high sorption capacity of alginate hydrogel, efficiency of AC to adsorb malodor and tissue degradation products and positive effects of Zn2+ on wound healing, the obtained composites have shown promising potentials for applications as multifunctional wound dressings.

The exibits presents a range of new multifunctional biomaterials for potential medical application. Biocompatible composites based on hydrogels of alginate, polyvinyl alcohol, and chitosan with incorporated bioactive agents such as silver nanoparticles, honey and activated charcoal particles with adsorbed povidone-iodine provide efficient release of the immoblized agents and antibacterial activity, which is attractive for applocation in wound dressing. Bioactive macroporous composites based on polzmer hzdrogels with bioceramic particles as well as metal foundations with multicomponent coatings are attractive as bone tissue implants. Finallz, dental inserts were developed for dentin replacement. In addition, the exibit will include a bioreactor system for cultivation of cancer cells in alginate hydrogels in 3-dimensionalenvironment, aimed to provide more reliable antitumor drug testing and development of personalized medical therapies.

Danas, razvoj novih kompozitnih biomaterijala za medicinsku primenu u terapiji rana bazira se na poznavanju različitih faktora povezanih sa procesom zarastanja i podrazumeva rešavanje specifičnih problema koji prate hronične rane. Cilj ove doktorske disertacije bio je razvoj novih kompozitnih hidrogelova na bazi alginata i čestica aktivnog uglja (AU) koji će u potencijalnoj primeni u tretmanu rana ispoljiti više povoljnih efekata. Naime, cilj je bio razvoj kompozita iz koga se, u dodiru sa biološkim fluidima, čestice AU kontrolisano i efikasno otpuštaju tokom dužeg perioda. Pri tome, čestice AU mogu biti nosači različitih aktivnih agenasa, dok bi alginatni hidrogel efikasno upijao vlagu. Kao model aktivne supstance izabrani su povidon-jod (PVP-I) i lignin model jedinjenja (LMJ) kao agensi koji ispoljavaju antimikrobno dejstvo. Rezultati istraživanje su pokazali da su metodom ekstruzije uspešno dobijene kompozitne Ca-alginatne čestice (CaA/AU) i to iz smeša alginata koncentracija u opsegu od 0,5 - 2 mas. % i AU u opsegu od 1-20 mas. %. Ispitivanjem kinetike otpuštanja AU iz suvih CaA/AU čestica u fiziološkom rastvoru utvrđeno je da je sastav optimalne smeše 0,5 mas. % alginata i 20 mas. % AU. Kinetika otpuštanja AU je uspešno opisana modelom unutrašnje difuzije osim u slučaju čestica dobijenih iz smeše optimalnog sastava gde je otpuštanje uzrokovano i erozijom čestica što je opisano Korsmejer-Pepasovim modelom Ekstruzijom smeše optimalnog sastava u rastvor za geliranje koji je sadržao jone cinka uspešno su dobjene i Zn0,5/V kompozitne čestice. Čestice na bazi Ca- i Zn-alginata dobijene iz smeše optimalnog sastava (Ca- i Zn0,5/V čestice) su u ii fiziološkom rastvoru otpustile oko 50 - 60 % ukupnog sadržaja AU tokom perioda od 5 dana koji je relevantan za tretman hroničnih rana. Ove čestice su zatim uspešno impregnirane prvom model supstancom (PVP-I), a u ispitivanjima desorpcije utvrđeno je da je PVP-I čvrsto vezan za čestice AU i da je stepen desorpcije u okolni algi, Today, the development of new composite biomaterials for wound treatment application is based on knowledge of different factors which affects the process of wound healing in order to identify solutions for specific problems related to chronic wounds. The aim of this thesis was to develop new composite hydrogels based on alginate and activated charcoal particles (AC) which would show beneficial effects in potential wound treatment application. Specifically, the aim was to develop composites which would during contact with biological fluids, release AC particles in a controlled and efficient manner during a prolonged period of time. Simultaneously, AC particles could be carriers of different active agents while alginate hydrogel would efficiently absorb the fluids. Povidone-iodine (PVP-I) and lignin model compounds (LMC) were chosen as model substances of active agents with antimicrobial activity. The results showed that the composite Ca-alginate beads (CaA/AC) were successfully obtained by extrusion method using mixtures of alginate in concentration range of 0.5-2 % w/w and AC in a concentration range of 1-20 % w/w. The diffusion model was successfully applied on the release kinetics experimental data of all groups of A/AC beads, except in the case of the beads obtained from the mixture with the optimal composition. In this case, the release of AC particles was a result of diffusion as well as erosion and the Korsmeyer-Peppas model was successfully applied. Zn0.5/H composite beads were successfully obtained by extrusion of optimal mixture in the gelling bath that contained Zn ions. The beads based on Ca- and Znalginate obtained from the optimal mixture (Ca- and Zn0.5/H beads) released around 50-60 % of iv the total AC content during a 5 day period, which is a period relevant for chronic wound treatment. These beads were successfully impregnated with the first model substance (PVP-I). The desorption studies established that PVP-I was firmly adsorbed onto AC particles

Today, the development of new composite biomaterials for wound treatment application is based on knowledge of different factors which affects the process of wound healing in order to identify solutions for specific problems related to chronic wounds. The aim of this thesis was to develop new composite hydrogels based on alginate and activated charcoal particles (AC) which would show beneficial effects in potential wound treatment application. Specifically, the aim was to develop composites which would during contact with biological fluids, release AC particles in a controlled and efficient manner during a prolonged period of time. Simultaneously, AC particles could be carriers of different active agents while alginate hydrogel would efficiently absorb the fluids. Povidone-iodine (PVP-I) and lignin model compounds (LMC) were chosen as model substances of active agents with antimicrobial activity. The results showed that the composite Ca-alginate beads (CaA/AC) were successfully obtained by extrusion method using mixtures of alginate in concentration range of 0.5-2 % w/w and AC in a concentration range of 1-20 % w/w. The diffusion model was successfully applied on the release kinetics experimental data of all groups of A/AC beads, except in the case of the beads obtained from the mixture with the optimal composition. In this case, the release of AC particles was a result of diffusion as well as erosion and the Korsmeyer-Peppas model was successfully applied. Zn0.5/H composite beads were successfully obtained by extrusion of optimal mixture in the gelling bath that contained Zn ions. The beads based on Ca- and Znalginate obtained from the optimal mixture (Ca- and Zn0.5/H beads) released around 50-60 % of iv the total AC content during a 5 day period, which is a period relevant for chronic wound treatment. These beads were successfully impregnated with the first model substance (PVP-I). The desorption studies established that PVP-I was firmly adsorbed onto AC particles, Danas, razvoj novih kompozitnih biomaterijala za medicinsku primenu u terapiji rana bazira se na poznavanju različitih faktora povezanih sa procesom zarastanja i podrazumeva rešavanje specifičnih problema koji prate hronične rane. Cilj ove doktorske disertacije bio je razvoj novih kompozitnih hidrogelova na bazi alginata i čestica aktivnog uglja (AU) koji će u potencijalnoj primeni u tretmanu rana ispoljiti više povoljnih efekata. Naime, cilj je bio razvoj kompozita iz koga se, u dodiru sa biološkim fluidima, čestice AU kontrolisano i efikasno otpuštaju tokom dužeg perioda. Pri tome, čestice AU mogu biti nosači različitih aktivnih agenasa, dok bi alginatni hidrogel efikasno upijao vlagu. Kao model aktivne supstance izabrani su povidon-jod (PVP-I) i lignin model jedinjenja (LMJ) kao agensi koji ispoljavaju antimikrobno dejstvo. Rezultati istraživanje su pokazali da su metodom ekstruzije uspešno dobijene kompozitne Ca-alginatne čestice (CaA/AU) i to iz smeša alginata koncentracija u opsegu od 0,5 - 2 mas. % i AU u opsegu od 1-20 mas. %. Ispitivanjem kinetike otpuštanja AU iz suvih CaA/AU čestica u fiziološkom rastvoru utvrđeno je da je sastav optimalne smeše 0,5 mas. % alginata i 20 mas. % AU. Kinetika otpuštanja AU je uspešno opisana modelom unutrašnje difuzije osim u slučaju čestica dobijenih iz smeše optimalnog sastava gde je otpuštanje uzrokovano i erozijom čestica što je opisano Korsmejer-Pepasovim modelom Ekstruzijom smeše optimalnog sastava u rastvor za geliranje koji je sadržao jone cinka uspešno su dobjene i Zn0,5/V kompozitne čestice. Čestice na bazi Ca- i Zn-alginata dobijene iz smeše optimalnog sastava (Ca- i Zn0,5/V čestice) su u ii fiziološkom rastvoru otpustile oko 50 - 60 % ukupnog sadržaja AU tokom perioda od 5 dana koji je relevantan za tretman hroničnih rana. Ove čestice su zatim uspešno impregnirane prvom model supstancom (PVP-I), a u ispitivanjima desorpcije utvrđeno je da je PVP-I čvrsto vezan za čestice AU i da je stepen desorpcije u okolni algi

In this work we have investigated possibilities for immobilization of lignin model compounds (LMCs) as potential antimicrobial agents on activated charcoal particles aimed for applications in wound dressings. LMC adsorption kinetics was determined for different initial LMC concentrations (0.1, 0.5 and 1.1 mg ml-1) by using UV-visible spectroscopy over 24 h when the equilibrium was reached. LMC adsorption on charcoal particles was confirmed by Fourier-transform infrared spectroscopy (FTIR). Adsorption kinetics was successfully modeled by the pseudo-second order Lagergren model while the adsorption isotherm at room temperature could be described by both Freundlich and Langmuir models showing satisfactory agreements. The maximal capacity of activated charcoal particles for LMCs according to the Langmuir model was 312.5 mg g-1. However, the immobilizates did not exhibit antibacterial activity against Pseudomonas aeruginosa indicating the need for further studies of LMC adsorption mechanism with the specific aim to elucidate exact compounds or functional groups responsible for antimicrobial action and their conformation on activated charcoal.