Macrophage-biomimetic porous Se@SiO2 nanocomposites for dual modal immunotherapy against inflammatory osteolysis

Abstract

Background Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (porous Se@SiO2 nanospheres) to manage inflammatory osteolysis. Results Macrophage membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) attenuated lipopolysaccharide (LPS)-induced inflammatory osteolysis via a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduced endotoxin levels and neutralized proinflammatory cytokines. Moreover, the release of Se could induce macrophage polarization toward the anti-inflammatory M2-phenotype. These effects were mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase (ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduced the inhibition of osteogenic differentiation caused by proinflammation cytokines, as confirmed through in vitro and in vivo experiments. Conclusion Our findings suggest that M-Se@SiO2 have an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 are a promising engineered nanoplatform for the treatment of osteolysis occurring after arthroplasty. Graphical Abstract

Ultrasmall PtAu2 nanoclusters activate endogenous anti-inflammatory and anti-oxidative systems to prevent inflammatory osteolysis

“…Acute/chronic inflammatory reactions and bone erosion at the bone-prosthesis interface caused by bacterial products such as lipopolysaccharides (LPS) can severely reduce the long-term stability of prostheses. Indeed, patients with inflammatory osteolysis may require multiple revision surgeries and even experience implant failure 5 . In addition to surgical intervention, medications such as bisphosphonates and non-steroidal anti-inflammatory drugs (NSAIDs) are often required to prevent the progression of inflammation and bone erosion.…”

Propionate and butyrate attenuate macrophage pyroptosis and osteoclastogenesis induced by CoCrMo alloy particles

“…The whole pathological process is closely related to the wear particles produced by the implant. These wear particles can be phagocytosed by surrounding macrophages [ 3 ]. After uptake of small wear-particles, these myeloid immune cells will be stimulated to secrete inflammatory cytokines including interleukin 1 beta (IL-1β), interleukin 6 (IL-6), prostaglandin E2 (PGE2), and tumour necrosis factor (TNF).…”

Sericin/Nano-Hydroxyapatite Hydrogels Based on Graphene Oxide for Effective Bone Regeneration via Immunomodulation and Osteoinduction

“… 6 In terms of bone implants, excessive M1 macrophages have been reported to induce the absorption of bone tissue, which is a major contributor to implant loosening and implantation failure. 54 In contrast, M2 macrophage polarization has been confirmed to construct an anti-inflammatory microenvironment to promote bone regeneration. 55 Sericin has been observed to have a mild inflammatory and low immunological response as a result of its high serine content.…”