In vivo molecular evidence of delayed titanium implant osseointegration in compromised bone

Optimization of implant osseointegration in patients with reduced bone healing potential is a challenge remaining in implant dentistry. Identification of the genes that are modulated during implant osseointegration in normal versus osteopenic bone is needed to successfully address these pertinent clinical needs. The present study aimed to assess the initial and early molecular events following titanium implant installation in normal and compromised bone in a rat tibia model. Peri-implant tissue from a well-defined tissue regeneration compartment was analyzed at 2 and 7 days post-surgery for the expression of select markers of inflammation, angiogenesis, bone resorption and bone formation. Impaired bone was induced by hindlimb unloading and validated using μCT. The essential step of angiogenesis preceding bone regeneration was evidenced for the peri-implant setting in healthy bone. Compromised bone significantly affected the angiogenesis-osteogenesis coupling in the initial phase (2 days post-surgery), with altered expressions of Vegfa and Epas1 coinciding with downregulated expressions of Col1a1, Bmp2, Bmp4, Alpl and Bglap. At 7 days post-implantation, differences between normal and compromised peri-implant bone were no longer observed. This in vivo molecular evidence of delayed implant osseointegration in compromised bone reassert modern strategies in implant development, such as surface modifications and bioengineered approaches, to improve implant osseointegration in compromised conditions.