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Ispitivanje mogućnosti kontrolisanog bubrenja i razgradnje alginatnih mikročestica u razblaženim rastvorima natrijum-citrata

dc.creatorMitrović, Dragana D.
dc.creatorStojkovska, Jasmina
dc.creatorObradović, Bojana
dc.description.abstractAlginate hydrogels are widely used in biomedicine due to alginate availability, hydrophilic nature, biocompatibility and biodegradability. Alginate microbeads are particularly attractive for applications in pharmacy and regenerative medicine due to high surface to volume ratio, low mass transfer limitations and simple implantation by injection. Aim of this work was to investigate possibilities for controlled degradation of alginate microbeads in cell culture medium (Dulbecco's modified Eagle's medium) with Na-citrate added in small concentrations (0.05-0.5 mM). Alginate microbeads (1.5% w/w, 800 μm in diameter) were produced by electrostatic droplet extrusion and evaluated over a period of 10 days regarding appearance, kinetics and degree of swelling as well as biomechanical properties determined in a novel bioreactor with mechanical stimulation under in vivo-like conditions in articular cartilage (10% strain, 337.5 μm/s compression rate). In the citrate concentration range investigated, microbeads initially swelled reaching an equilibrium value (~150-170% with respect to the initial mass), upon which they appeared stable for a certain period of time (1 to over 7 days) followed by bead bursting and degradation. This degradation process indicated that Na+ from the solution initially replaced Ca2+ bound mainly to COO- groups in polymannuronate sequences inducing electrostatic repulsion of polymer chains and, consequently, swelling of the beads. Citrate ions assisted in this process by forming insoluble calcium citrate. Thus, the specific rate of the bead swelling increased with the increase in citrate concentration approaching a maximal value of ~0.34 d-1. In the last phase, the beads burst into pieces, which slowly continued to degrade by replacement of Ca2+ bonded to polyguluronate blocks in the egg-box structure. Compression moduli for packed beds of control, freshly produced microbeads, and microbeads swelled at the equilibrium degree after 3 days of staying in 0.2 mM Na-citrate solution were 136.6±2.8 and 30.8±1.3 kPa, respectively. By day 7 in this solution, the beads still appearing structurally intact, further lost their mechanical strength due to continued polymer chain relaxation so that the compression modulus was 20.7 to 22.6 kPa owed almost solely to undegraded polyguluronate parts. Results of these studies are important from a fundamental standpoint for determination of structure and degradation mechanisms of alginate hydrogels but also from a practical point of view for optimization of hydrogel properties and behavior for potential applications in controlled drug release as well as in tissue engineering.en
dc.description.abstractU ovom radu je ispitivana mogućnost kontrolisane degradacije mikročestica kalcijum-alginata (1,5 mas.%, 800 μm prečnik) u medijumu za kulture ćelija uz male koncentracije natrijum-citrata (0,05-0,5 mM). Određeni su kinetika i stepen bubrenja čestica, i njihove mehaničke karakteristike u bioreaktoru sa mehaničkom stimulacijom. Rezultati su ukazali na mehanizam razgradnje po kome Na+ prvo zamenjuju Ca2+ vezane za manuronske ostatke, dovodeći do bubrenja čestica, a zatim u drugoj fazi zamenjuju i Ca2+ čvršće vezane za guluronske ostatke što dovodi do pucanja čestica. Proces bubrenja je bio limitiran brzinom ispravljanja polimernih lanaca, a specifična brzina je pri povećanju koncentracije citrata težila maksimalnoj vrednosti od ~0,34 d-1. Dobijeni rezultati su značajni za potencijalnu primenu alginatnih hidrogelova za kontrolisano otpuštanje terapeutika kao i u inženjerstvu
dc.publisherAssociation of Chemical Engineers of Serbia
dc.sourceHemijska industrija
dc.subjecthydrogel degradationen
dc.subjectcontrolled releaseen
dc.subjectbioreactor with mechanical stimulationen
dc.subjectdegradacija hidrogelovasr
dc.subjectkontrolisano otpuštanjesr
dc.subjectbioreaktor sa mehaničkom stimulacijomsr
dc.titleControlled swelling and degradation studies of alginate microbeads in dilute natrium citrate solutionsen
dc.titleIspitivanje mogućnosti kontrolisanog bubrenja i razgradnje alginatnih mikročestica u razblaženim rastvorima natrijum-citratasr
dc.citation.other64(4): 253-263

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