Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis.

Abstract

Osseointegration seems to be a foreign body reaction equilibrium due to the complicated interactions between the immune and skeletal systems. The heterogeneity of the osteoimmune microenvironment in the osseointegration of implant materials remains elusive. Here, a single-cell study involving 40043 cells is conducted, and a total of 10 distinct cell clusters are identified from five different groups. A preliminary description of the osteoimmune microenvironment revealed the diverse cellular heterogeneity and dynamic changes modulated by implant properties. The increased immature neutrophils, Ly6C ⁺ CCR2^hi monocytes, and S100a8^hi macrophages induce an aggressive inflammatory response and eventually lead to the formation of fibrous capsule around the stainless steel implant. The enrichment of mature neutrophils, FcgR1^hi and differentiated immunomodulatory macrophages around the titanium implant indicates favorable osseointegration under moderate immune response. Neutrophil-depletion mice are conducted to explore the role of neutrophils in osseointegration. Neutrophils may improve bone formation by enhancing the recruitment of BMSCs via the CXCL12/CXCR3 signal axis. These findings contribute to a better knowledge of osteoimmunology and are valuable for the design and modification of 'osteoimmune-smart' biomaterials in the bone regeneration field.