Immunocompatibility of metallic-ion doped bioactive glasses and titanium-based implants for musculoskeletal regeneration

Musculoskeletal disorders (MSDs) are conditions that can impair the body’s movement intissues of the musculoskeletal system. Since the risk to develop MSDs increases withage, its burden on patients and healthcare systems is expected to keep rising. Nowadays,the treatment of MSDs relies on ineffective drug administration and on surgery forbiomaterial implantation, as a short-term solution. Due to the need for new therapies, Iworked with two types of optimized biomaterials: doped bioactive glasses (BG) andtitanium-based discs. Incorporating metallic ions, such as silver, copper and tellurium, intothe surface of BG can not only prevent infection, but also modulate the immune responseand enhance other biological processes. On the titanium-based discs, a patentedchemical treatment (CT) was applied, which has been previously shown to enhancehydroxyapatite deposition, while also impeding bacterial colonization. In this thesis, theimpact of culturing immune cells in contact with these biomaterials was evaluated. Ourresults on the silver doping revealed high toxicity in PBMCs, while tellurium did not impactcell viability. Copper influenced T-cell differentiation while its undoped control impactedother immune cells through cytokine overexpression. Conversely, titanium-based discsdid not impact PBMC viability. However, the polished untreated control showed anincreased percentage of Th2 cells, while decreasing the Th17 one. CT discs restoredT-cell phenotype and cytokine secretion to basal values. CT discs increased MSCmetabolic activity, while BG require pre-treatment to remove the initial ion burst releaseand enhance cell adhesion. Proteomic studies revealed that MSCs cultured withcopper-doped BG secrete EVs enriched in pro-angiogenic factors. Our findings suggestminimal impact of biomaterials on MSC paracrine signalling, as supplementation withphysiological MSC-EV doses had little effect on immune and endothelial cells.