Functional bioreactor characterization to assess potentials of nanocomposites based on different alginate types and silver nanoparticles for use as cartilage tissue implants

Abstract

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.

Validation of a novel perfusion bioreactor system in cancer research

“…Furthermore, these bioreactors can be useful tools also in drug screening, cancer research and characterization of novel biomaterials. As an example, we have previously shown that cytotoxicity studies of Ag/alginate nanocomposite hydrogels in cartilage explant tissue cultures in a biomimetic bioreactor with dynamic compression applied in a regime relevant for articular cartilage have indicated the nanocomposite biocompatibility without signs of cytotoxicity [12]. These results were in accordance with the functionality that these hydrogels exhibited in burn treatments in rats while contrary to moderate cytotoxic effects found in chondrocyte monolayers [12].…”

Interdisciplinary crossover for rapid advancements - collaboration between medical and engineering scientists with the focus on Serbia

“…For instance, biomimetic bioreactors, which imitate physiological conditions in a certain tissue or organ, are primarily being developed for tissue engineering purposes. Still, these bioreactors also provide physiologically relevant studies of novel biomaterials and interactions of biomaterials with cells and tissues [22][23][24]. Thus, by this approach it is possible to address the in vitroin vivo gap that is, discrepancies between results obtained in traditional monolayer cell cultures (in 2D environment) and those found in animal studies [25][26][27].…”

“…Thus, by this approach it is possible to address the in vitroin vivo gap that is, discrepancies between results obtained in traditional monolayer cell cultures (in 2D environment) and those found in animal studies [25][26][27]. It was shown, for example, that nanocomposite alginate hydrogels with AgNPs had moderate to strong cytotoxic effects on chondrocytes in monolayers, while such effects were entirely absent in 3D bioreactor cultures of immobilized chondrocytes in alginate microbeads as well as in cartilage tissue cultures in a direct contact with the nanocomposite hydrogel [23,28]. The results obtained in the bioreactor cultures were in agreement with the enhancement of wound healing without any adverse effects found in the treatment of 2 nd degree burns in rats by the same nanocomposite hydrogels [21].…”

A comprehensive review of the polymer‐based hydrogels with electrochemically synthesized silver nanoparticles for wound dressing applications

“…The size distribution of electrochemically synthesized (galvanostatic method) AgNPs in Ag/Alg colloid solutions and hydrogels was evaluated by TEM imaging and the distribution was found to be fairly narrow for colloids and hydrogels based on low-viscosity alginate, in the 3 to 18 nm range, with average values around 8 to 9 nm. 140 On the other hand, medium-viscosity alginate hydrogels and colloids contained a broader AgNPs size distribution (3-28 nm), with larger average particle diameters (9-12 nm), 140 indicating that the choice and properties of the polymer matrix play an important role in controlling the AgNPs characteristics. Similar results were obtained for chitosan-containing hydrogels, which were analyzed by DLS as also discussed above.…”