Production of nanocomposite alginate microbeads with electrochemically synthesized silver nanoparticles (AgNPs) based on electrostatic extrusion technique was investigated with respect to potentials for utilization in pharmaceutical and biomedical applications. It was shown that electrochemical synthesis of AgNPs results in reduction of practically all Ag+ ions present in the initial solution yielding stable Ag/alginate colloid solutions that were demonstrated to be suitable for sterilization, manipulation, and electrostatic extrusion with retention of AgNPs. Presence of AgNPs in alginate colloid solutions had negligible effects on the size of the produced Ag/alginate microbeads, which was chiefly determined by the applied electrostatic potential during the extrusion. On the other hand, incorporation of AgNPs within the alginate hydrogel induced slight changes in biomechanical properties determined in a biomimetic bioreactor, so that packed beds of nanocomposite Ag/alginate microbeads exhibited slightly higher dynamic compression modulus as compared to that of control alginate microbeads (154 ± 4 and 141 ± 2 kPa, respectively). On the other hand, equilibrium unconfined compression modulus was significantly lower for nanocomposite microbeads as compared to that of controls (34 ± 2 and 47 ± 0.5 kPa, respectively). [Projekat Ministarstva nauke Republike Srbije, br. III 45019 i br. Eureka E!6749

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Intervertebral discs are normally exposed to a variety of loads and stresses but hydrostatic pressure (HP) could be the main biosignal for chondrogenic cell differentiation and maintenance of this tissue. Although there are simple approaches to intermittently expose cell cultures to HP in separate material testing devices, utilization of biomimetic bioreactors aiming to provide in vitro conditions mimicking those found in vivo, attracts special attention. However, design of such bioreactors is complex due to the requirement of high HP magnitudes (up to 3 MPa) applied in different regimes mimicking pressures arising in intervertebral disc during normal daily activities. Furthermore, efficient mass transfer has to be facilitated to cells within 3D scaffolds, and the engineering challenges include avoidance or removal of gas bubbles in the culture medium before pressurization as well as selection of appropriate, biocompatible construction materials and maintenance of sterility during cultivation. Here, we review approaches to induce HP in 2D and 3D cell cultures categorized into 5 groups: (I) discontinuous systems with direct pressurization of the cultivation medium by a piston, (II) discontinuous systems with indirect pressurization by a compression fluid, (III) continuous systems with direct pressurization of the cultivation medium, static culture, (IV) continuous systems with culture perfusion, and (V) systems applying HP in conjunction with other physical signals. Although the complexity is increasing as additional features are added to the systems, the need to understand HP effects on cells and tissues in a physiologically relevant, yet precisely controlled, environment together with current technological advancements are leading towards innovative bioreactor solutions.

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Development of drugs is a complex, time- and cost-consuming process due to the lack of standardized and reliable characterization techniques and models. Traditionally, drug screening is based on in vitro analysis using two-dimensional (2D) cell cultures followed by in vivo animal testing. Unfortunately, application of the obtained results to humans in about 90 % of cases fails. Therefore, it is important to develop and improve cell-based systems that can mimic the in vivo-like conditions to provide more reliable results. In this paper, we present development and validation of a novel, user-friendly perfusion bioreactor system for single use aimed for cancer research, drug screening, anti-cancer drug response studies, biomaterial characterization, and tissue engineering. Simple design of the perfusion bioreactor provides direct medium flow at physiological velocities (100?250 ?m s-1) through samples of different sizes and shapes. Biocompatibility of the bioreactor was confirmed in short term cultivation studies of cervical carcinoma SiHa cells immobilized in alginate microfibers under continuous medium flow. The results have shown preserved cell viability indicating that the perfusion bioreactor in conjunction with alginate hydrogels as cell carriers could be potentially used as a tool for controlled anti-cancer drug screening in a 3D environment. [Projects of the Serbian Ministry of Education, Science and Technological Development, Grant no. 451-03-68/2020-14/200135 and Grant no. 451-03-68/2020-14/ 200042]

In this work, functional characterization of biomaterials concerning potential application as articular cartilage implants was performed by using a biomimetic bioreactor with dynamic compression in the physiological regime (10% strain, 0.84 Hz frequency, 1 h on/1 h off). Specifically, two alginate types with low (LG) and high (HG) guluronic/mannuronic residue ratios with electrochemically synthesized silver nanoparticles (AgNPs) were evaluated. HG Ag/alginate hydrogels were clearly indicated as potential candidates due to better initial mechanical properties as compared to LG hydrogels (dynamic compression modulus of ~60 vs. ~40 kPa) as well as the mechanical stability displayed during 7 days of dynamic compression. Cytotoxicity studies in 3D bovine cartilage explant cultures under dynamic compression have shown negligible effects as compared to standard 2D monolayers of bovine chondrocytes where moderate cytotoxicity was observed. Finally, experimental and mathematical modeling studies revealed different mechanisms of AgNP release under physiological‐like bioreactor conditions as compared to static conditions. Overall, the results clearly demonstrate bioreactor advantages in characterization and selection of candidate biomaterials as well as potentials to bridge the in vitro‐in vivo gap. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 755–768, 2019.

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