| Polymeric and metal oxide micro- and nanoparticles are being increasingly introduced into biomedical applications such as tissue engineering as well as in consumer products, which has boosted extensive research towards developing predictive paradigms of their (bio-)activity. The core hypotheses which are tested in the four interrelated studies of this work is that the (bio-)activity of the particles is defined not only by their intrinsic properties such as the composition/structure, functional groups, surface charge, and size/morphology, but also on the concentration of particles which in turn is determined by specific applications.;The first study addresses the effect of the concentration of the polysebacic anhydride microparticles on the cellular viability of chondrocytes (cartilage cells) and on the properties of in vitro grown tissue. I found that, contrary to the reported safety of polyanhydrides, the polysebacic anhydride -based microparticles are cytotoxic to chondrocytes (cartilage cells) at concentrations relevant to delivery in articular cartilage engineering. The cytotoxicity is explained by the lipotoxicity from the polysebacic anhydride degradation products. The available data allow suggesting that the bioactivity of polysebacic anhydride polymer is collectively and uniquely determined by its degradation rate and hydrophobicity which requires further verification. It is found that the cytotoxicity of polysebacic anhydride can be mitigated significantly by administering of bovine serum albumin.;The second study verifies the importance of functional groups of polymer particles in the model system of polyacrylate-based nanoparticles and chondrocytes in a 3D agarose hydrogel scaffold. From this study, the charge on the functional groups of the polymers is found to have a significant effect on their bioactivity. Specifically, the polyacrylate-based nanoparticles are shown to be biocompatible (at 0.2% w/v) to chondrocytes in terms of cellular viability. However, they exhibit bioactivity which is detrimental to the synthesis of extracellular matrix even at such low concentrations. An inverse correlation is established between mechanical strength and the negative surface charge of these nanoparticles. The cause for poor matrix synthesis is suggested to be the disruption of the inter-cellular signaling process by higher anionicity. The main impact of this study is that the utility of anionically charged polymeric particles in articular cartilage engineering should be scrutinized carefully, since it is shown that for a clinically relevant scaffold system such as agarose hydrogels, these particles may act detrimentally.;Study 3 focuses on the (bio-)activity of redox-active metal oxide nanoparticles toward chondrocytes. For the first time, nanoceria is shown to greatly improve the biochemical as well as mechanical properties of the cartilage tissue grown in vitro. In particular, when nanoceria is suspended in the growth medium, it offered significant chondroprotectivity against interleukin-1α and partial prevention of the matrix degradation. However, when nanoceria is directly embedded into the constructs, it does not offer any protection against interleukin-1α. These results show the great potential of nanoceria in improving tissue properties and combating the arthritic inflammation. If the mode of nanoceria administration and cellular uptake are further optimized, the long term protection of cartilage can be achieved.;Study 4 addresses the effects of nanoparticle size and morphology on the adsorption and dispersion of the ferric (hydr)oxide nanoparticles in the presence of surfactants, which is relevant to the dispersion of the nanoparticles in their application in image and contrast agents, cancer therapy, ferrofluids, paints, and cosmetics. The first experimental evidence is obtained for the dependence of the surface density, speciation, and packing order of adsorbed fatty acids on the nanoparticle size and morphology. The conditions under which fatty acids form self-assembled monolayers and bilayers on such nanoparticles in water are distinguished and the electric polarization of the nanoparticles is demonstrated to be a powerful tool for manipulating the interfacial properties of the nanoparticles. Specifically, an increase in nanosize improves the adsorption capacity and affinity of hematite nanoparticles, in agreement with the nanosize-induced changes in the structural and electronic properties of the nanoparticles. Consequently, an increase in nanosize of hematite nanoparticles improves the packing order of laurate and hence hydrophobicity of the nanoparticles provided a similar hexagonal habit of these nanoparticles. (Abstract shortened by UMI.). |
