The Effect of Hydroxyapatite Nanocrystals on Osseointegration of Titanium Implants: An In Vivo Rabbit Study

Osseointegration is dependent on implant surface characteristics, including surface chemistry and topography. The presence of nanosized calcium phosphates on the implant surface is interesting to investigate since they affect both the nanotopography and surface chemistry, forming a bone mineral resembling surface. In this work, the osseointegration of titanium implants with and without the presence of hydroxyapatite (HA) nanocrystals has been evaluated in vivo. The integration was examined using removal torque measurements and real-time polymerase chain reaction (RT-PCR) analysis. The study was performed using two healing time points, 3 and 12 weeks. The results showed that the torque needed to remove the implants was insignificant between the non- and HA-coated implants, both at weeks 3 and 12. The RT-PCR, however, showed significant differences for osteoblast, osteoclast, and proinflammation markers when HA nanocrystals were present. 1. Introduction During the last decades, novel implants have been developed with the aim of finding optimal conditions for osseointegration. It is well known that factors, such as surface chemistry and surface topography, influence osseointegration [1]. However, the biological influence of nanorough surfaces is a relatively new area of research and highly interesting since several studies have indicated that nanotopography can enhance osseointegration [2–4]. When combining the two surface entities, nanoroughness and bone-like chemistry, for example, by using nanosized hydroxyapatite (HA), a synergistic effect can be generated [2]. HA is a widely known and frequently used material, which is often being utilized as relatively thick implant coatings. Recently, techniques have been developed which made it possible to coat implants with a monolayer of HA nanoparticles. Such thin HA layers have proven to increase the wettability and thereby increase the surface energy of the implant. Increasing the surface energy is speculated to affect the cell and protein adhesion resulting in improved osseointegration [5, 6]. Moreover, the adsorption of plasma proteins, such as fibronectin and laminin, has been suggested to increase when implants have been surface-modified with calcium and phosphorous [7]. There are many suggested techniques to determine if osseointegration has occurred [8–13]. Commonly, the removal torque of the implant and histology of the bone-implant interface are examined, both after specific healing times. Most often these two methods are combined, even though not on the same implant, in order to reach a more complete