Nanofeatures of Biomaterials and their Impact on the Inflammatory Response

Abstract: Nanomaterials offer an advantage over traditional biomaterials since cells naturally communicate via nanoscale interactions. The extracellular matrix, for example, modulates adhesion and cellular functions via nanoscale features. Thus incorporating nanofeatures into biomaterials may promote tissue regeneration, however in certain forms and doses nanomaterials can also cause harm. A thorough understanding of cell-nanomaterial interactions is therefore necessary to better design functional biomaterials. This thesis focuses on evaluating the effect of nanofeatures on inflammation using two different models: nanoporous alumina and hydroxyapatite nanoparticles (HANPs).The inflammatory response caused by in vitro exposure of macrophages to nanoporous alumina, with pore diameters of 20nm and 200nm, was investigated. In addition in vivo studies were performed by implantation of nanoporous membranes in mice. In both cases the 200nm pore diameter elicited a stronger inflammatory response.Nanoporous alumina with 20, 100 and 200nm pores were loaded with Trolox, a vitamin E analogue, in order to scavenge ROS produced by primary human polymorphonuclear (PMNC) and mononuclear (MNCs) leukocytes. Unloaded alumina membranes stimulated greater ROS production from PMNCs cultured on 20nm versus 100nm pores. This trend reversed when PMNCs were cultured on Trolox loaded membranes since Trolox eluted slower from 20nm than 100nm and 200nm pores. ROS produced from PMNCs was reduced between 8-30% when cultured on Trolox loaded membranes. For MNCs, ROS production was not affected by pore size. However when the alumina was loaded with Trolox ROS production was quenched by 95%.HANPs with distinct morphologies (long rods, sheets, dots, and fibers) were synthesized via hydrothermal and precipitation methods. The HANPs were then exposed to PMNCs, MNCs, and the human dermal fibroblast (hDF) cell line. Changes in cell viability, ROS, morphology, and apoptotic behavior were evaluated. PMNC and hDF viability decreased following exposure to fibers, while the dot particles reduced MNC viability. Fibers stimulated greater ROS production from PMNCs and MNCs, and caused apoptotic behavior in all cell types. Furthermore, they also stimulated greater capsule thickness in vivo, suggesting that nanoparticle morphology can significantly influence acute inflammation.The outcome of this thesis, confirms the importance of understanding how nanofeatures influence inflammation.