Akademik Veri Yönetim Sistemi
World Immune Regulation Meeting XVIII 2024, Chur, İsviçre, 13 - 16 Mart 2024, cilt.18, sa.56, ss.67
Maintaining bone density, strength, and overall skeletal health relies on the delicate equilibrium between bone resorption and formation. Due to the lack of sufficient autograft volume, large bone defects commonly require additional material, both as void filler and as a source of osteogenic material. This project aims to develop novel bone forming substitutes and analyse their effects on immune cells. We conducted experiments to assess the immunological characteristics of the examined materials by utilizing PBMC. The cell cultures were designed to investigate the development of an immune response to direct contact between immunologically active cells and the tested materials. PBMC cultures were finely-tuned utilizing commercially accessible compounds, including beta-tricalcium phosphate, tyramine-modified hyaluronic acid (THA) gel, filtrated/unfiltrated bone particles (monolayer/transwell cultures), agarose, fibrin sealant (Evicel®), and their combinations. Experiments involved the incorporation of tritiated thymidine, assessing cell viability using propidium iodide in flow cytometry, and targeted proteomics by Proximity Extension Assay. The data demonstrated a marginal elevation in the proliferative activity of cells exposed to specific test materials, including gels like THA, agarose, or Evicel®. These findings were notably lower compared to positive controls with phytohemagglutinin and a mixture of anti-CD2, anti-CD3 and anti-CD28 mAbs. Cell activation in the presence of all materials emphasizes the importance of careful consideration to prevent potential chronic inflammation in response to implanted materials. Pathway analysis highlighted matrisome-, plasmacytoma-, apoptosis- and immune response-related proteins. We next selected proteins related to bone remodelling from the targeted proteomics (OLINK T-92, inflammation and immune response panels) data and investigated the profiles exhibited by various conditions concerning these markers. Thus, we focused on proteins including CSF−1, IFN−gamma, IL−1 alpha, LAP TGF−beta−1, OPG, TNF, and TRANCE. The OPG/TRANCE balance provides insights into the molecular basis of bone remodelling. PBMC response to Evicel® and also its combination with filtered bone particles point out to reduced bone resorption and potentially excessive bone formation.