D3.406 - Novel bone materials selectively modulate the human immune response to favor remodeling over acute inflammation

The field of osteoimmunology holds that successful bone regeneration relies on a specific immune environment that balances inflammation with repair. While chronic inflammation drives bone resorption, a transient, specific immune response is essential to initiate healing. Conventional bone substitutes are often evaluated for osteoconductivity, overlooking their critical interaction with the local immune system. This study investigates the immunomodulatory properties of a fibrin-based scaffold combined with calcined bovine bone particles.

Human peripheral blood mononuclear cells (PBMCs) were exposed to combinations of fibrin sealant (EVICEL), calcined bone particles, and control particles for up to 48 hours. The immune response was characterized. Inflammatory secretome was analyzed using high-throughput targeted proteomics (Olink) focusing on inflammation and bone remodeling panels. To define the specific cellular phenotypic shifts, we performed high-dimensional single-cell mass cytometry (CyTOF) at 24 and 48 hours, utilizing a broad panel of 30 markers.

Proteomic analysis revealed a shift toward regeneration, characterized by a high OPG/TRANCE ratio in EVICEL and bone combinations that limits bone resorption, the upregulation of repair-centric factors like VEGFA and TGF-β1, and the simultaneous suppression of tissue-degrading enzymes such as MMP-1 and MMP-10 compared to inflammatory controls. CyTOF profiling revealed dampened T-cell activation (CD25, CXCR3; p<0.001) yet preserved survival markers (CD127, CD28). On the other hand, CD14⁺CD16⁺ monocytes and CD11c⁺ dendritic cells were significantly sustained (p<0.0001), coinciding with upregulated tissue-repair signatures (CCR4, CXCR5) and expanded γδ T cells.

Fibrin-based matrices differentially regulate immunity to favor regeneration, suppressing nonspecific T-cell inflammation while preserving myeloid precursors and inducing an osteogenic proteomic shift characterized by high OPG/TRANCE ratios.