Bioactive manganese-decorated titanium implants for osteoporotic bone regeneration

Abstract

Bone defect repair in osteoporosis remains a major clinical problem due to the persistent abnormal inflammatory response and imbalance of bone homeostasis. Manganese (Mn) ions have been proven to have dual effects of promoting immunomodulation and osteogenesis, showing great potentials for bone tissue regeneration in osteoporotic bone defects. In the present study, a novel Mn2+-releasing coating on titanium (Ti) substrates was prepared via biomimetic mussel-inspired chemical modification. Notably, the combination of polydopamine (PDA) and Mn2+ endowed Ti@PDA + Mn with diverse bioactivities. In addition to excellent biocompatibility and osteogenic capability, Ti@PDA + Mn exhibited the ability to regulate intracellular reactive oxygen species (ROS) and induce macrophage to polarize towards M2 phenotype by the secretion of anti-inflammatory cytokines such as IL-10 and osteogenic-related cytokines such as TGF-β, establishing an osteoimmune microenvironment that facilitates bone tissue repair, establishing an osteoimmune microenvironment that facilitates bone tissue repair. In the ovariectomized osteoporosis rat model, Ti@PDA + Mn exhibited enhanced osseointegration in femoral bone defects demonstrated by micro-CT, histopathology, and immunohistochemistry at 2 and 6 weeks after surgery. Finally, the potential signaling pathway of Mn2+ regulating osteogenesis has been further studied. Transcriptome sequencing revealed the significant regulatory functions of Mn2+, which upregulated the HIF-1 signaling pathway to enhance bone regeneration. The mechanism of Mn-enhanced osteogenesis developed in this study could provide theoretical and practical insights for enhancing implant-to-bone osseointegration in osteoporotic bone defects.

Keywords

• Manganese
• Osteoinductivity
• Immunomodulation
• Osteoporosis
• Osseointegration