20.500.12556/DKUM-84162 Development of pH Responsive Polysaccharide Based Wound Dressings doctoral disertation Razvoj ph odzivnih polisaharidnih medicinskih obližev In the scope of the Doctoral Dissertation, a polysaccharide based stimuli-responsive smart material with controlled drug release was developed by using electrospinning technique, which allowed to form stimuli-responsive nanofibers with rapid visual detection of pH change in the wound bed along with anti-inflammatory activity. Incorporation of halochromic dyes into electrospun nanofibers has been an intriguing area for wound healing applications. Furthermore, it is known that the pH value within the wound milieu directly and indirectly influences all biochemical reactions taking place in the process of wound healing. It has been proven that the surface pH of a wound plays an important role in wound healing as it helps control infection and increases the antimicrobial activity, oxygen release, angiogenesis, protease activity, and bacterial toxicity. Therefore, visual pH monitoring without the need of removing the wound dressing was one of the aims of the Doctoral Dissertation. Produced stimuli-responsive wound dressings were characterized according to their morphological and chemical properties using well-known techniques such as, rheometry, conductivity, Scanning Electron Microscopy (SEM),CIE Lab, Thermogravimetric Analysis (TGA), UV/VIS Spectrophotometry, and Attenuated Total Reflection Infra-Red Spectroscopy (ATR-IR). Responsiveness of the nanofibers were achieved by integration of different halochromic dyes [bromocresol green (BCG), bromothymol blue (BTB) and thymol blue (TB)] to obtain a range of pH values. To tackle the problem of leaching of the dyes, a complexing agent; poly-diallyldimethylammonium chloride (PDADMAC) was integrated and an analysis on the formation of complexation was performed by using pH-potentiometric titration and Quartz Crystal Microbalance with Dissipation (QCM-D) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) techniques. Additionally, release tests were performed to prove that the leaching of the halochromic dyes is reduced significantly up to 97%. Furthermore, the responsiveness of the nanofibers was investigated by exposing the nanofibers to different buffer solutions with pH values 4, 7 and 10. The color change of the nanofibers were analyzed using the CIE Lab system while a visual color shift was observed according to their characteristics. Lastly, diclofenac (DFC), an anti-inflammatory drug molecule was integrated to the system and drug release studies were performed by using Franz diffusion cells. A controlled release of the drug molecule (DFC) to the wound bed is achieved and quantitative evaluations were done. Consequently, the drug release from the smart wound dressings were identified to have two separate profiles during the release. The mathematical models that were identified to fit to the kinetics are, first-order, Korsmeyer-Peppas, and Higuchi release model, confirming the controlled drug release. V okviru doktorske disertacije je bil s postopkom elektropredenja razvit polisaharidni pametni material, ki je odziven na zunanje dražljaje in omogoča nadzorovano sproščanje zdravil. Odzivna nanovlakna omogočajo hitro vizualno zaznavanje spremembe pH vrednosti v predelu rane in ob tem aktivirajo protivnetno delovanje. Vgrajena halokromna barvila v elektropredena nanovlakna so izjemno zanimiva iz vidika spremljanja celjenja ran. Poleg tega je znano, da pH vrednost v okolju rane neposredno in posredno vpliva na vse biokemiske reakcije, ki potekajo pri procesu celjenja ran. Dokazano je, da ima pH na površini rane pomembno vlogo pri njenem celjenju, saj pomaga nadzorovati okužbe in povečuje protimikrobno aktivnost, sproščanje kisika, angiogenezo, aktivnost proteaz in bakterijsko toksičnost. Zato je bil eden od ciljev doktorske naloge razviti material, ki bo omogočal vizualno spremljanje pH rane, brez bolečega odstranjevanja obliža z rane. V okviru doktorske disertacije je bil, z uporabo tehnike elektropredenja, razvit odzivni pametni material na osnovi polisaharidov, s sposobnostjo hkratnega nadzorovanega sproščanja zdravil s protivnetnim delovanjem in hitrim vizualnim zaznavanjem spremembe pH v okolju rane. Odzivnost elektropredenih nanovlaken je bila dosežena z vključitvijo različnih halokromnih barvil (bromokrezol zeleno (BCG), bromotimol modro (BTB) in timol modro (TB)), z različnim barvnim sprektrom v odvisnosti od pH. Za reševanje problema izpiranja barvila iz materiala je bilo uporabljeno kompleksirno sredstvo, poli-dialildimetilamonijev klorid (PDADMAC). Tvorba kompleksa je bila raziskana s pH-potenciometrično titracijo, kvarčno mikrotehnico s desipacijo (QCM-D) in sekundarna masna ionska spektrometrija (ToF-SIMS) . Oblikovana odzivna nanovlakna so bila okarakterizirana z vidika njihovih morfoloških lasnostni, z uporabo vrstične elektronske mikroskopije (SEM), in kemijske zgradbe, z uporabo infrardeče spektroskopije (ATR-FTIR) . V okviru naloge so bili opravljeni testi sproščanja z uporabo UV/VIS spektropskopije, ki so dokazali, da se izpiranje halokromnih barvil ob uporabi PDADMAC znatno zmanjša, tudi do 99%. Odzivnost nanovlaken je bila raziskana z izpostavljanjem nanovlaken različnim pufrskim raztopinam z vrednostmi pH 4, 7 in 9. Barvne spremembe nanovlaken so bile spektrofotometrično ovrednotene z uporabo sistema CIE L*a*b*. V zadnjem delu doktorske naloge razvoja multifunkcijskega materiala je bila v sistem elektropredilne raztopine vključena molekula protivnetnega zdravila diklofenak (DFC). Razvit končni material je bil testiran z vidika njegove biokompatibilnosti, izvedena je bila tudi študija sproščanja zdravila z uporabo Franzovih difuzijskih celic. DFC se je nadzorovano sproščal v PBS, ki simulira okolje rane, pri čemer so bile opravljene tudi kvantitativne ocene. stimuli-responsive polysaccharides wound dressings halochromism controlled drug release smart materials stimulativno odzivni polisaharidi obliži za rane halokromizem nadzorovano sproščanje zdravil pametni materiali true true false [B. Elveren] Angleški jezik Slovenski jezik Doktorsko delo/naloga 2023-04-21 14:48:09 2023-10-06 09:32:28 2023-10-21 03:05:47 0000-00-00 00:00:00 2023 0 Maribor 0 Maribor XXIII, 144 str. 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 [604.2:547.458]:615.468(043.3) 169277187 DOK_Elveren_Beste_2023.pdf DOK_Elveren_Beste_2023.pdf 1 D904366733EDBBDE1D662E8157F8B5F5 b4ee6c4a5d657b0955b09e5e5d71ffcbdcd782925bcd031af964a599a999327a 0904c131-603c-11ee-9597-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=173184 Fakulteta za strojništvo 0 0 0