Human T-Cell Responses to Metallic Ion-Doped Bioactive Glasses.

Biomaterials are extensively used as replacements for damaged tissue with bioactive glasses standing out as bone substitutes for their intrinsic osteogenic properties. However, biomaterial implantation has the following risks: the development of implant-associated infections and adverse immune responses. Thus, incorporating metallic ions with known antimicrobial properties can prevent infection, but should also modulate the immune response. Therefore, we selected silver, copper and tellurium as doping for bioactive glasses and evaluated the immunophenotype and cytokine profile of human T-cells cultured on top of these discs. Results showed that silver significantly decreased cell viability, copper increased the T helper (Th)-1 cell percentage while decreasing that of Th17, while tellurium did not affect either cell viability or immune response, as evaluated via multiparametric flow cytometry. Multiplex cytokines assay showed that IL-5 levels were decreased in the copper-doped discs, compared with its undoped control, while IL-10 tended to be lower in the doped glass, compared with the control (plastic) while undoped condition showed lower expression of IL-13 and increased MCP-1 and MIP-1ß secretion. Overall, we hypothesized that the Th1/Th17 shift, and specific cytokine expression indicated that T-cells might cross-activate other cell types, potentially macrophages and eosinophils, in response to the scaffolds.

Surface Functionalization of Ti6Al4V-ELI Alloy with Antimicrobial Peptide Nisin.

Implant-associated infections are a severe global concern, especially in the case of orthopedic implants intended for long-term or permanent use. The traditional treatment through systemic antibiotic administration is often inefficient due to biofilm formation, and concerns regarding the development of highly resistant bacteria. Therefore, there is an unfulfilled need for antibiotic-free alternatives that could simultaneously support bone regeneration and prevent bacterial infection. This study aimed to perform, optimize, and characterize the surface functionalization of Ti6Al4V-ELI discs by an FDA-approved antimicrobial peptide, nisin, known to hold a broad antibacterial spectrum. Accordingly, nisin bioactivity was also evaluated by in vitro release tests both in physiological and inflammatory pH conditions. Several methods, such as X-ray photoelectron spectroscopy (XPS), and Kelvin Probe atomic force microscopy confirmed the presence of a physisorbed nisin layer on the alloy surface. The functionalization performed at pH 6-7 was found to be especially effective due to the nisin configuration exposing its hydrophobic tail outwards, which is also responsible for its antimicrobial action. In addition, the first evidence of gradual nisin release both in physiological and inflammatory conditions was obtained: the static contact angle becomes half of the starting one after 7 days of soaking on the functionalized sample, while it becomes 0° on the control samples. Finally, the evaluation of the antibacterial performance toward the pathogen Staphylococcus aureus after 24 h of inoculation showed the ability of nisin adsorbed at pH 6 to prevent bacterial microfouling into biofilm-like aggregates in comparison with the uncoated specimens: viable bacterial colonies showed a reduction of about 40% with respect to the un-functionalized surface and the formation of (microcolonies (biofilm-like aggregates) is strongly affected.

New Generation of Hybrid Materials Based on Gelatin and Bioactive Glass Particles for Bone Tissue Regeneration.

Hybrid scaffolds based on bioactive glass (BAG) particles (<38 µm), covalently linked to gelatin (G*) using 3-glycidoxypropyltrimethoxysilane (GPTMS), have been studied for bone bioengineering. In this study, two glass compositions (13-93 and 13-93B20 (where 20% of the SiO2 was replaced with B2O3)) were introduced in the gelatin matrix. The Cfactor (gelatin/GPTMS molar ratio) was kept constant at 500. The hybrids obtained were found to be stable at 37 °C in solution, the condition in which pure gelatin is liquid. All hybrids were characterized by in vitro dissolution in Tris(hydroxymethyl)aminomethane (TRIS) solution (for up to 4 weeks) and Simulated Body Fluid (SBF) (for up to 2 weeks). Samples processed with 13-93B20 exhibited faster initial dissolution and significantly faster precipitation of a hydroxyapatite (HA) layer. The faster ion release and HA precipitation recorded from the G*/13-93B20 samples are attributable to the higher reactivity of borosilicate compared to silicate glass. The MC3T3-E1 cell behavior in direct contact with the hybrids was investigated, showing that the cells were able to proliferate and spread on the developed biomaterials. Tailoring the glass composition allows us to better control the material's dissolution, biodegradability, and bioactivity. Bioactive (especially with 13-93B20 BAG) and biocompatible, the hybrids are promising for bone application.