1,720,998 research outputs found
PRIPRAVA AMINOKISLINSKIH IN PEPTIDNIH POLISAHARIDNIH DERIVATOV TER NJIHOVA UPORABA KOT BIOMATERIALI
Get PDFThe derivatization of the polysaccharide dextran with N-protected amino acids (Boc-L-Phenylalanine, BocGlycine, Boc-L-Cysteine, and Boc-L-Cysteine-S-Trt) and peptides (Boc-L-DiPhenylalanine, Boc DiGlycine, and 2,5-diketopiperazine) as the basis for biomaterial preparation is presented in this Doctoral Dissertation. Such prepared dextran derivatives are intended to mimic the proteoglycan complex (PGs), one of the most important structural and functional biomacromolecules in the extracellular matrix (ECM) of tissue. Nowadays, developments in biomaterials are focusing increasingly on the preparation and use of biomimetic molecular structures to achieve positive results in tissue engineering (TE) and drug delivery. Designing and synthesizing these biomimetic materials, however, requires sophisticated chemical and material preparation methods, knowledge that is, currently, unexplored.
In this work, we developed a suitable procedure for dextran derivatization, and investigated the most optimal reaction or deprotection conditions (temperature and time) and isolation/purification methods. The structures of the obtained BocPhe-Dex, BocGly-Dex, BocCys-Dex, and BocSTLC-Dex were analyzed with FTIR, NMR, SEC-MALS, and EA. The results showed that dextran derivatization was successful in all cases except in the case of dextran derivatization with BocCys. Investigation of the effect of the derivatization conditions and purification on the stability, purity, and other important chemical and physical properties of the obtained product, showed that the temperature and time of derivatization do not have a bigger effect on the products\u27 properties, while the purification method, on the other hand, has. Its effect is visible in the product\u27s purity and mass yields of products prepared under the same reaction conditions.
Derivatization of dextran with peptides (Boc-L-DiPhenylalanine, BocDiGlycine, and 2,5-diketopiperazine) was performed using the CDI coupling agent or Amberlite-IR 120 as a catalyst. The products were analyzed with FTIR and 1H and 13C NMR. The results showed successful dextran derivatization in the case of BocDiPhenylalanine and BocDiGlycine, while, in the case of 2,5-diketopiperazine, a reaction covalent bond with the dextran was not confirmed.
BocPhe-Dex and BocSTLC-Dex were selected as the most optimal amino acid-dextran derivatives for further preparation of 3D formulations in the shape of nanoparticles (NPs). Nanoparticles were prepared with the emulsion/solvent evaporation method from the obtained BocPhe-Dex and BocSTLC-Dex products (prepared in the first stage of this Doctoral Dissertation). SEM analysis showed that the prepared NPs were homogeneous and nicely spherical, with an average dry diameter of 325 ± 118 nm in the case of BocSTLC-Dex, and 1039 ± 382 nm in the case of NPs prepared from BocPhe-Dex. All the prepared NPs retained their proper spherical shape and stability during the acidic treatment, and so confirmed their potential for further functionalization and applications for drug delivery. The BocSTLC-Dex NPs were also evaluated with cell viability tests, which showed that the prepared NPs were not cytotoxic, one of the most important characteristics for the drug delivery applications of NPs.
This work serves as a basis for further studies on the derivatization of polysaccharides with amino acids and peptides, and their application in tissue engineering or drug delivery.V tej doktorski disertaciji je predstavljena derivatizacija polisaharida dekstrana z N-zaščitenimi aminokislinami (Boc-L-Fenilalanin, BocGlicin, Boc-L-Cistein in Boc-L-Cistein-S-Trt) in peptidi (Boc-L-DiFenilalanin, Boc-DiGlicin, in 2,5-diketopiperazin) kot osnova za pripravo biomateriala. Tako pripravljeni derivati dekstrana so namenjeni posnemanju proteoglikanskega kompleksa (PG), ene najpomembnejših strukturnih in funkcionalnih biomakromolekul v zunajceličnem matriksu (ECM) tkiva. Dandanes se razvoj biomaterialov vse bolj osredotoča na pripravo in uporabo biomimetičnih molekularnih struktur za doseganje pozitivnih rezultatov v tkivnem inženirstvu (TE) in dostavi zdravil. Oblikovanje in sintetiziranje teh biomimetičnih materialov pa zahteva sofisticirane kemične in materialne metode priprave, znanje, ki je trenutno neraziskano.
V tem delu smo razvili ustrezen postopek za derivatizacijo dekstrana in raziskali najbolj optimalne reakcijske pogoje (temperatura in čas) ter metode izolacije/čiščenja. Lastnosti dobljenih BocPhe-Dex, BocGly-Dex, BocCys-Dex in BocSTLC-Dex smo analizirali s FTIR, NMR, SEC-MALS in EA. Rezultati so pokazali, da je bila derivatizacija dekstrana uspešna v vseh primerih, razen v primeru derivatizacije dekstrana z BocCys. Raziskava vpliva pogojev derivatizacije in čiščenja na stabilnost, čistost in druge pomembne kemijske in fizikalne lastnosti dobljenega produkta je pokazala, da temperatura in čas derivatizacije nimata večjega vpliva na lastnosti produktov, medtem ko metoda čiščenja pa ima, saj je njen učinek viden v čistosti produkta in masnih izkoristkih produktov, pripravljenih pod enakimi reakcijskimi pogoji.
Derivatizacija dekstrana s peptidi (Boc-L-DiFenilalanin, BocDiGlicin in 2,5-diketopiperazin) je bila izvedena z uporabo spojnega sredstva CDI ali Amberlite-IR 120 kot katalizatorja. Produkte smo analizirali s FTIR in NMR. Rezultati so pokazali uspešno derivatizacijo dekstrana v primeru BocDiFenilalanina in BocDiGlicina, medtem ko v primeru 2,5-diketopiperazina reakcijska kovalentna vez z dekstranom ni bila potrjena.
BocPhe-Dex in BocSTLC-Dex sta bila izbrana kot najbolj optimalna aminokislinsko-dekstranska derivata za nadaljnjo pripravo 3D formulacij v obliki nanodelcev (NP). Iz dobljenih produktov BocPhe-Dex in BocSTLC-Dex (pripravljenih v prvi fazi te doktorske disertacije) smo pripravili nanodelce z metodo evaporacije emulzije/topila. Analiza SEM je pokazala, da so pripravljeni NP-ji homogeni in lepo sferični, s povprečnim suhim premerom 325 ± 118 nm v primeru BocSTLC-Dex in 1039 ± 382 nm v primeru NP-jev, pripravljenih iz BocPhe-Dex. Vsi pripravljeni NP-ji so ohranili pravilno sferično obliko in stabilnost med obdelavo s kislino in tako potrdili svoj potencial za nadaljnjo funkcionalizacijo in aplikacije za dostavo zdravil. NP-ji BocSTLC-Dex so bili ovrednoteni tudi s testi viabilnosti celic, ki so pokazali, da pripravljeni NP-ji niso citotoksični, kar je ena najpomembnejših značilnosti za aplikacije NP-jev za dostavo zdravil.
To delo služi kot podlaga za nadaljnje študije o derivatizaciji polisaharidov z aminokislinami in peptidi ter njihovi uporabi v tkivnem inženiringu ali dostavi zdravil
Optimizacija i dubinska analiza alginatnih nanoceluloznih hidrogelova za 3D printanje krvožilnih i kožnih sustava
No full textIn recent decades, tissue engineering and regenerative medicine have received much attention. Although tissue engineering covers a wide range of applications, this work focuses mainly on the optimization and processing of hydrogels for such applications. Numerous properties of 3D printed and crosslinked alginate and nanocellulose hydrogels were analyzed, such as the calcium leaching process important for tissue regeneration processes, tensile properties to gain insight into the elastic and/or plastic properties of materials important for pressurized vascular systems, diffusion processes to demonstrate the permeability of the scaffolds for the transfer of nutrients to the cells and testing of the cytotoxicity of the material. Important biomaterial properties such as biocompatibility and controlled degradation for biomedical applications have been reached and optimized. It was observed that higher calcium concentration positively influences mechanical properties of the hydrogels. During tensile testing as well as shrinking and swelling tests, material anisotropy important for application in vascular systems was observed. The obtained results are promising for future applications in biomedicine and tissue engineering.U zadnjih nekoliko desetljeća velika pažnja usmjerena je na inženjering tkiva i regenerativnu medicinu. Iako tkivni inženjering uključuje širok spektar primjena, ovaj rad fokusira se uglavnom na optimizaciju i razvoj hidrogelova za takvu primjenu. Analizirana su brojna svojstva 3D isprintanih i umreženih alginatnih i nanoceluloznih hidrogelova kao što su proces ispiranja kalcija važnog za procese regeneracije tkiva, zatim ispitivanja vlačnim povlačnjem kako bi se dobio uvid u elastična, odnosno plastična svojstva materijala važna za primjenu u krvožilnim sustavima. Zatim, pocesi difuzije za dokazivanje permeabilnosti hidrogela, vrlo važnog svojstva koje omogućuje prijenos nutrijenata do oštećenog tkiva, te na kraju ispitivanje citotoksičnosti materijala. Postignuta su i optimizirana važna svojstva biomaterijala za biomedicinske primjene, kao što su biokompatibilnost i kontrolirana degradacija. Uočeno je da veća koncentracija kalcija pozitivno utječe na mehanička svojstva hidrogelova. Tijekom testova rastezanja te testova bubrenja i skupljanja uočena je anizotropija materijala važna kod primjene u krvožilnim sustavima. Dobiveni rezultati obećavajući su za buduće primjene u biomedicini i tkivnom inženjeringu
Sinteza polimerov, vsebujočih betain, holin in karnitin, za zdravljenje kožnih ran
Get PDFIn this study, we explored the development of cationized 2-hydroxyethyl cellulose (HEC) and succinylated polyallylamine (PAA) in conjunction with polyvinyl alcohol (PVA) for potential applications as antimicrobial wound dressings. Quaternary ammonium compounds are known for their broad-spectrum antimicrobial properties against both Gram-negative and Gram-positive bacteria, but their non-selectivity can lead to high cytotoxicity. To improve the biocompatibility of the cationic materials investigates two distinct approaches. The first approach involves reducing the cationic nature of protonated PAA at a pH below 8.3 through amidation reaction with succinic anhydride. Gradual reduction of the cationic charge is achieved by varying the molar ratios of succinic anhydride during the reaction process. Notably, this reaction can be carried out in an aqueous solution, eliminating potential issues associated with solvent removal. The second part of this thesis focuses on introducing cationic charge by covalently binding naturally occurring quaternary ammonium compounds, such as betaine hydrochloride (BET HCl), choline chloride (ChCl), and carnitine hydrochloride (carnitine). Using 1,1′-carbonyldiimidazole (CDI), we quaternized HEC in anhydrous DMSO, with a detailed investigation of the reaction mechanism by isolating and characterizing intermediate products. This same procedure was applied to form a cationic dimer between BET HCl and ChCl. The chemical structures of the resulting materials were characterized using attenuated total reflectance infrared spectroscopy (ATR-IR) and nuclear magnetic resonance (NMR). The quantification of cationic and total charge was determined through polyelectrolyte and potentiometric titration, respectively. While succinylated PAA exhibited the anticipated biological properties associated with the reduction of cationic characteristics, the same behaviour was not observed for quaternized materials. High cytotoxicity and low antimicrobial properties in the derivatized HEC may be attributed to inadequate purification and the sensitivity of fibroblasts. We produced electrospun non-woven mats incorporating PVA and these derived materials using a single-needle electrospinning machine. The average diameter of the fibres was determined through scanning electron microscopy (SEM) images. Despite the cytotoxicity and the absence of significant antimicrobial properties in these materials, they exhibit potential as effective cationic flocculants for wastewater treatment. Further investigations are pending to address purification issues and make slight adjustments to the procedure to potentially scale up production. These materials still hold promise for applications in both biomedical and environmental chemistry.Doktorska disertacija obravnava razvoj materialov, ki v svoji strukturi vsebujejo pozitivno nabite dušikove skupine, ki so uporabni na področju celjenja ran. Pozitivno nabiti materiali imajo sposobnost uničevanja mikrobov in so tako še posebno zanimivi predvsem na področju raziskovanja v biomedicini, saj je poznana njihova vloga pri celjenju ran. Znano je, da so dologotrajna vnetja pri celjenju ran pereča težava, ki so pogosto povzročena z mikrobno kontaminacijo bakterij. Kot možna rešitev, ter možnost pospešenega in uspešnega celjenja ran, je ključnega pomena razvoj oblog za rane, ki imajo antimikrobne lastnosti. Doktorska naloga predstavlja oblikovanje in razvoj materialov s pozitivno nabitim nabojem, z namenom njihove uporabe prav za aplikacije kot so obloge za rane. Za izdelavo takšnih željenih materialov je prav tako velik poudarek na postopkih, ki so bili aplicirani za njihovo modifikacijo. Pomembno je, dase pri samih metodah modifikacije uporabljajo topila z relativno nizkim vplivom na okolje in toksičnostjo, ter večinoma biokompatibilne komponente. Slednje označuje pripravljene materiale kot primerne tako za okolje kakor za aplikacije pri celjenju ran
Optimizacija i dubinska analiza alginatnih nanoceluloznih hidrogelova za 3D printanje krvožilnih i kožnih sustava
No full textIn recent decades, tissue engineering and regenerative medicine have received much attention. Although tissue engineering covers a wide range of applications, this work focuses mainly on the optimization and processing of hydrogels for such applications. Numerous properties of 3D printed and crosslinked alginate and nanocellulose hydrogels were analyzed, such as the calcium leaching process important for tissue regeneration processes, tensile properties to gain insight into the elastic and/or plastic properties of materials important for pressurized vascular systems, diffusion processes to demonstrate the permeability of the scaffolds for the transfer of nutrients to the cells and testing of the cytotoxicity of the material. Important biomaterial properties such as biocompatibility and controlled degradation for biomedical applications have been reached and optimized. It was observed that higher calcium concentration positively influences mechanical properties of the hydrogels. During tensile testing as well as shrinking and swelling tests, material anisotropy important for application in vascular systems was observed. The obtained results are promising for future applications in biomedicine and tissue engineering.U zadnjih nekoliko desetljeća velika pažnja usmjerena je na inženjering tkiva i regenerativnu medicinu. Iako tkivni inženjering uključuje širok spektar primjena, ovaj rad fokusira se uglavnom na optimizaciju i razvoj hidrogelova za takvu primjenu. Analizirana su brojna svojstva 3D isprintanih i umreženih alginatnih i nanoceluloznih hidrogelova kao što su proces ispiranja kalcija važnog za procese regeneracije tkiva, zatim ispitivanja vlačnim povlačnjem kako bi se dobio uvid u elastična, odnosno plastična svojstva materijala važna za primjenu u krvožilnim sustavima. Zatim, pocesi difuzije za dokazivanje permeabilnosti hidrogela, vrlo važnog svojstva koje omogućuje prijenos nutrijenata do oštećenog tkiva, te na kraju ispitivanje citotoksičnosti materijala. Postignuta su i optimizirana važna svojstva biomaterijala za biomedicinske primjene, kao što su biokompatibilnost i kontrolirana degradacija. Uočeno je da veća koncentracija kalcija pozitivno utječe na mehanička svojstva hidrogelova. Tijekom testova rastezanja te testova bubrenja i skupljanja uočena je anizotropija materijala važna kod primjene u krvožilnim sustavima. Dobiveni rezultati obećavajući su za buduće primjene u biomedicini i tkivnom inženjeringu
Optimizacija i dubinska analiza alginatnih nanoceluloznih hidrogelova za 3D printanje krvožilnih i kožnih sustava
No full textIn recent decades, tissue engineering and regenerative medicine have received much attention. Although tissue engineering covers a wide range of applications, this work focuses mainly on the optimization and processing of hydrogels for such applications. Numerous properties of 3D printed and crosslinked alginate and nanocellulose hydrogels were analyzed, such as the calcium leaching process important for tissue regeneration processes, tensile properties to gain insight into the elastic and/or plastic properties of materials important for pressurized vascular systems, diffusion processes to demonstrate the permeability of the scaffolds for the transfer of nutrients to the cells and testing of the cytotoxicity of the material. Important biomaterial properties such as biocompatibility and controlled degradation for biomedical applications have been reached and optimized. It was observed that higher calcium concentration positively influences mechanical properties of the hydrogels. During tensile testing as well as shrinking and swelling tests, material anisotropy important for application in vascular systems was observed. The obtained results are promising for future applications in biomedicine and tissue engineering.U zadnjih nekoliko desetljeća velika pažnja usmjerena je na inženjering tkiva i regenerativnu medicinu. Iako tkivni inženjering uključuje širok spektar primjena, ovaj rad fokusira se uglavnom na optimizaciju i razvoj hidrogelova za takvu primjenu. Analizirana su brojna svojstva 3D isprintanih i umreženih alginatnih i nanoceluloznih hidrogelova kao što su proces ispiranja kalcija važnog za procese regeneracije tkiva, zatim ispitivanja vlačnim povlačnjem kako bi se dobio uvid u elastična, odnosno plastična svojstva materijala važna za primjenu u krvožilnim sustavima. Zatim, pocesi difuzije za dokazivanje permeabilnosti hidrogela, vrlo važnog svojstva koje omogućuje prijenos nutrijenata do oštećenog tkiva, te na kraju ispitivanje citotoksičnosti materijala. Postignuta su i optimizirana važna svojstva biomaterijala za biomedicinske primjene, kao što su biokompatibilnost i kontrolirana degradacija. Uočeno je da veća koncentracija kalcija pozitivno utječe na mehanička svojstva hidrogelova. Tijekom testova rastezanja te testova bubrenja i skupljanja uočena je anizotropija materijala važna kod primjene u krvožilnim sustavima. Dobiveni rezultati obećavajući su za buduće primjene u biomedicini i tkivnom inženjeringu
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
