OBJECTIVES: Evaluate hBMP-2 expression following gene delivery from plasmid multilayers formed on sandblasted titanium in vitro and bone formation around similarly prepared implant surfaces in vivo. MATERIALS AND METHODS: Multilayers of cationic lipid/rhBMP-2 plasmid DNA complex (LDc) and anionic hyaluronic acid (HA) was assembled on sandblasted-dual acid etched pure titanium disks or implant surfaces using layer-by-layer (LBL) assembly. Gene delivery and hBMP-2 expression in cells exposed to the LDc multilayers was measured in vitro. To determine the effect of BMP delivery from such multilyaers in vivo, roughened implants coated with BMP-2 LDc multilayers or uncoated control implants (n = 15 for both) were implanted in the femurs of NZW rabbits. After 2, 4, 8 weeks, femurs were retrieved and prepared for histomorphometric evaluation (n = 5 rabbits per time point). RESULTS: MC3T3-E1 cells cultured directly on the BMP-2 LDc coated titanium disks showed EGFP and hBMP-2 expression after 48 h in culture. Increased gene delivery occurred by increasing the number of assembly layers when cells were cultured for 48 h. Cells cultured on LDc coated surfaces had significantly higher cell viability than control cells cultured on uncoated porous titanium surfaces. Histologic observation of the implants showed that after 4 weeks healing, the bone to implant contact (BIC) on the LDc coated surface was much lower than that on the control surface, but didn't reach significant. In contrast, the percentage of bone within the implant's threads was significantly higher than the control group (P = 0.047). CONCLUSION: The BMP-2 gene coated sandblasted dual acid etched titanium implants slightly accelerated early bone formation around implants.