The present study assessed in vivo new bone formation around titanium alloy implants chemically grafted with macromolecules bearing ionic sulfonate and/or carboxylate groups. Unmodified and grafted Ti-6Al-4V exhibiting either 100% carboxylate, or 100% sulfonate, or both carboxylate and sulfonate groups in the percent of 50/50 and 80/20 were bilaterally implanted into rabbit femoral condyle. Neither toxicity nor inflammation were observed for all implants tested. After 4 weeks, peri-implant new bone formation varied as a function of the chemical composition of the titanium surfaces. The percent bone-implant contact (BIC) was the lowest (13.4 +/- 6.3%) for the implants modified with grafted carboxylate only. The value of BIC on the implants with 20% sulfonate (24.6 +/- 5.2%) was significantly (P < 0.05) lower than that observed on 100% sulfonate (38.2 +/- 13.2%) surfaces. After both 4 and 12 weeks post-implantation, the BIC value for implants with more than 50% sulfonate was similar to that obtained with the unmodified Ti-6Al-4V. The grafted titanium alloy exhibiting either 100% sulfonate or carboxylate and sulfonate (50% each) groups promoted bone formation. Such materials are of clinical interest because, they do not promote bacteria adhesion but, they support new bone formation, a condition which can lead to osseointegration of bone implants while preventing peri-implant infections.