Modulating bone ingrowth into titanium implants by growth factor delivery and mechanical loading.

摘要

Replacement of joints in both dentistry and orthopedics using titanium implants has been highly successful, but failures remain due to either inadequate initial fixation with host bone or long-term maintenance of this bond. Techniques of controlled drug delivery of bioactive molecules such as growth factors and biomechanical stimulation have repeatedly been utilized to increase bone growth in skeletal applications, and in this study were adapted and applied to increasing titanium implant integration with host bone.; For controlled drug delivery, the osteogenic transforming growth factor beta1 (TGFbeta1) was encapsulated in poly-lactic-co-glycolic acid (PLGA) microspheres, which released in a controlled fashion up to 28 days. In vitro tests demonstrated significantly increased proliferation and 3D migration into a hollow titanium implant up to 28 days when human mesenchymal stem cells (hMSCs), osteoprogenitors likely involved in bone repair after injury, were stimulated by TGFbeta1 release from PLGA microspheres. For in vivo tests, hollow titanium implants to incorporate PLGA microspheres were custom fabricated and unicortically placed in the humeri of skeletally mature New Zealand white rabbits. After 4 weeks healing, those animals with PLGA microspheres releasing TGFbeta1 showed significant increases in bone ingrowth parameters, when compared to controls without TGFbeta1. Compared to a rapid release system of TGFbeta1 adsorbed to gelatin sponge, much lower doses of TGFbeta1 were required to increase bone ingrowth when using controlled release.; To test mechanical stimulation, micromechanical forces of 200 mN and 1 Hz, below the level to cause implant loosening and failure, were applied to titanium implants inserted into the femur of New Zealand white rabbits for 10 min/day for 12 consecutive days after a 6 week healing period. Static and dynamic histomorphometric parameters were all significantly higher for peri-implant bone of loaded implants as compared to unloaded contralateral controls.; The results of this study support controlled growth factor delivery and micromechanical stimulation to increase peri-implant bone around titanium implants, with potential clinical use to improve short and long-term implant fixation. Hollow titanium implants with PLGA microspheres could also be modified for multiple growth factor release, release for time points up to weeks or months, and even cellular delivery.