Initiator-particle synergy enables microrough, osteoconductive polymethyl methacrylate bone cement

Conventional polymethyl methacrylate (PMMA) bone cement formulated with benzoyl peroxide (BPO) initiator is biotolerant, cytotoxic, and incapable of true osseointegration. Here, we introduce a transformative surface-engineering strategy that confers controlled microroughness and enhanced biocompatibility to PMMA bone cement through a synergistic combination of tri-n-butyl borane (TBB) as a polymerization initiator and optimized polymer particle size. Formulating PMMA-TBB with 10-20 µm particles generated hemispherical micro-protrusions that increased surface area by 68% (Sdr), compared with only 8% for conventional PMMA-BPO. TBB's rapid, oxygen-insensitive polymerization preserved particle contours and reduced free radical generation by ∼90%, markedly mitigating polymerization-induced cytotoxicity. The microrough PMMA-TBB supported significantly greater osteoblast attachment, proliferation, and differentiation in vitro, uniquely induced contact osteogenesis in vivo with concomitant upregulation of osteogenic genes, and yielded a 4-6-fold increase in bone-cement interfacial strength. Importantly, PMMA-TBB also enhanced endothelial cell adhesion and function, indicating a more permissive microenvironment for angiogenic-osteogenic coupling at the bone-cement interface. This initiator-particle design principle establishes PMMA-TBB as the first microrough PMMA bone cement with genuine osteoconductive and osseointegrative properties, shifting PMMA fixation from a passive, biotolerant paradigm toward biologically active integration in orthopedic surgery. STATEMENT OF SIGNIFICANCE: Polymethyl methacrylate (PMMA) bone cement has remained essentially unchanged for decades, functioning as a biotolerant filler with no true capacity for osseointegration. This study overturns that paradigm by introducing an initiator-particle synergy that enables, for the first time, controlled microroughness engineering in PMMA bone cement. By pairing tri-n-butyl borane (TBB) polymerization initiator with optimally sized polymer particles, we achieved hemispherical micro-protrusions that preserved particle contours, reduced free radical toxicity, and created a biologically active interface. The resulting PMMA-TBB cement uniquely induced contact osteogenesis and significantly strengthened bone-cement integration. This work establishes a transformative design principle for orthopedic biomaterials, shifting PMMA bone cement from passive fixation toward bioactive, osteoconductive integration.