Title

Age-related changes in the response of primary human osteoblasts to implant materials

Date of Completion

January 2002

Keywords

Health Sciences, Medicine and Surgery|Health Sciences, Dentistry|Health Sciences, Human Development

Degree

Ph.D.

Abstract

Osseointegration is critical for the success of implant therapy in orthopedic surgery and dentistry. It is important to know if the process of osseointegration in elderly patients is different from that in younger patients. Since bone biology can differ in male and female patients, the effect of gender on osseointegration was also evaluated in this study. Primary human osteoblasts (HOBs) were used in in vitro cell/implant studies. Ti-6Al-4V is an extensively used implant material for patient treatment and was used as a substrate. The cell cultures from cancellous bone fragments obtained in orthopedic surgeries on healthy patients were characterized to be osteoblastic. HOBS from older female patients showed a decreased ability to attach to the implant surface, while male patients failed to show age-related change on cell adhesion at an early stage. The proliferation rate was not changed with aging or gender. Collagen synthesis showed a age-related decrease in both genders which was not statistically significant. Long-term mineralization assays showed age-related decreases in HOB/implant cultures in female patients, but not in male patients. Bone formation showed by fluorescent staining disclosed that osteoprogenitor number in cell cultures from females decreased significantly in old patients. Message levels of bone matrix proteins demonstrated age related decrease on implant surfaces for females. ^ Growth factors, like TGF-β, have significant anabolic effects on bone formation. TGF-β1 was investigated in the human osteoblast-implant system to try to offset the decreased cell responses to implant materials found in osteoblasts from older female patients. Our data showed that TGF-β1 had biphasic effect on HOB mineralization and continuous administration is necessary to obtain an anabolic effect. Continuous use of TGF-β1 at 0.2 ng/ml increased mineralization of HOBs from old female patients on implants. It also significantly promoted HOBS differentiation and matrix protein message levels in old female patients. However, it had no effect on the proliferation rate of HOBs. ^ In summary, our data showed significant age-related changes on HOBS from female patients responding to the implant material Ti-6Al-4V. In male patients, this type of age-related changes was not found. The use of TGF-β1 can offset some of the age-related changes in HOBs from female patients. ^