The role of dendritic cells in the immunomodulation to implanted biomaterials

Considering the substantial role played by dendritic cells(DCs) in the immune system to bridge innate and adaptive immunity,studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effects in facilitating the adaptive immunity of codelivered antigens. However, the effect of the intrinsic properties of biomaterials on dendritic cells has not been clarified. Recently, researchers have begun to investigate and found that biomaterials that are nonadjuvant could also regulate the immune function of DCs and thus affect subsequent tissue regeneration. In the case of proteins adsorbed onto biomaterial surfaces,their intrinsic properties can direct their orientation and conformation, forming “biomaterial-associated molecular patterns(BAMPs)”. Thus, in this review, we focused on the intrinsic physiochemical properties of biomaterials in the absence of antigens that affect DC immune function and summarized the underlying signaling pathways. Moreover, we preliminarily clarified the specific composition of BAMPs and the interplay between some key molecules and DCs, such as heat shock proteins(HSPs) and high mobility group box 1(HMGB1). This review provides a new direction for future biomaterial design, through which modulation of host immune responses is applicable to tissue engineering and immunotherapy.

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

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+CCR2hi monocytes,and S100a8hi 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,FcgR1hi 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.