Simple Zinc Metallic Particle Doping Transforms Ceramic Bone Cement Therapeutic Performance

Ceramic bone cements are widely utilized for bone defect repair, but their therapeutic effects remain unsatisfying due to their slow degradation, limited bioactivity, and lack of antibacterial properties. This study demonstrates a simple yet effective strategy to transform their performance by doping zinc (Zn), in the form of metal particles, into the bone cement matrix. Zn particle doping endows the cement with hierarchical porosity, sustained Zn²⁺ release, and reactive oxygen species generation. The Zn particle-doped bone cement exhibits potent antibacterial activity against methicillin-resistant Staphylococcus aureus, with mechanistic insights revealed through comparative in vitro and in vivo studies. In a critical-sized bone defect model, Zn-doped cement demonstrates superior bioresorption, tissue infiltration, and osteogenic capacity compared to pure cement. Among the tested formulations, cements containing 5–10 wt.% Zn particles achieved the most favorable balance of antibacterial efficacy, degradation, and bone regeneration, thereby representing the most promising candidates for clinical translation. In addition, the pivotal role of the SMAD3 signaling pathway in Zn²⁺-mediated cell migration and osteogenesis is identified. This study not only delivers a clinically promising ceramic bone cement but also pioneers a versatile and scalable strategy for transforming bone cement properties through Zn biodegradable metal particle doping.