The goal of the study was the evaluation of the effect of biochemical surface modification by collagen on the bone response to acid-etched titanium surfaces. Fibrillar type I porcine collagen was adsorbed and covalently linked to acid-etched Ti disks and implants. Adhesion, growth, and specific alkaline phosphatase (ALP) activity of osteoblast-like SaOS2 cells were evaluated. Implants in the femur and tibia of rabbit were performed for 2 and 4 weeks and relevant bone to implant contact (BIC) was evaluated by histomorphometry. Results show that cell morphology and growth are controlled by the rough acid-etched implants topography. Specific metabolic activity (ALP) is significantly increased by the collagen overlayer. Importantly, surface modification by collagen increases the speed of periimplant bone formation, resulting in significantly higher BIC both in femur and tibia at 2 weeks. These results suggest that morphological (surface topography) and biochemical (surface linking of bioactive molecules) cues can cooperate and yield multifunctional implant surfaces. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.