Synthetic peptide-conjugated titanium alloy for enhanced bone formation in vivo

There are growing demands for bioactive titanium implants that could shorten the healing period, promote faster rehabilitation, and thereby increase the success rate of treating patients with poor bone quality. A synthetic receptor-binding peptide mimicking bone morphogenetic protein-2 (BMP-2) was covalently linked to a titanium alloy with two types of topography--machined (TiMA) and rough (TiGB)--by using a chemical conjugation process. In vivo osseointegration capacity was evaluated chronologically using histomorphometric analysis at 2, 4, and 8 weeks after implantation in the distal femurs of rabbits. In the histologic examinations, peri-implant bone formation was more active around TiGB than TiMA. Compared to the control groups (nonconjugated TiMA and TiGB) at 2, 4, and 8 weeks, the peptide-conjugated groups (TiMA-P and TiGB-P) had more mature new bone, thicker trabeculae, more rapid bone maturation, and higher affinity index (percentage of new bone contact length) in histomorphometric analysis. Particularly, differences in the affinity index between the peptide-conjugated and nonconjugated groups were more pronounced at the early phase of peri-implant healing (2 and 4 weeks). However, at 8 weeks, enhanced bone formation was less prominent according to peptide conjugation, especially in specimens with a rough surface. The titanium alloys in the rabbit femurs led to a significant increase of bone growth when modified with bioactive peptides, especially during the early phase of bone healing. These results confirm that biochemical modifications of titanium surfaces can enhance the rate of bone healing compared with that of untreated titanium surfaces.