The use of porous coated, uncemented Implants for hip and bone replacements has become widespread. These implants are designed to permit direct bone attachment for stabilization and relief of arthritic pain and loss of function; yet this process at a cellular level Is poorly understood. Our studies will use a human osteobIast culture for studying the formation of the interface between the Implant biomaterial and the bone cell and Its mineralized matrix. Various implant materials will be tested to increase our understanding of the components and the process by which bone forms in response to implants for successful osseointegration. The primary goal of this study is to analyze the mechanism of cell attachment to the implant biomaterial so that surface modifications can be performed for optimal osseointegration: Titanium, titanium alloy and various preparations of titanium alloy substrates will first be used in these studies.
Aim 1 is to measure cell attachment, proliferation, and morphology on implant disks. Human cortico-cancellous bone chips, plastic and glass will be used as controls.
Aim 2 will involve assaying the production of four major bone matrix proteins, Type I collagen, osteonectin, osteocalcin, and fibronectin. The ability of the matrix to mineralize will also be assayed. Differences in extracellular -matrix production will be assessed by analyzing protein secretion by metabolic labelling experiments and by determining the mRNA levels of these proteins by Northern and dot blot analysis.
Aim 3 is to determine the role of integrins (the cell receptors for extracellular matrix proteins) in the initial attachment process to the implant material. Changes in the expression of various integrins on the cell surface of the human osteoblast will be assessed.
Aim i s to evaluate various modified surfaces of implant biomaterials for their ability to promote osteoblast attachment, differentiation and mineralization. The use of an in vitro human osteoblast culture system will be invaluable in the study of the mechanism by which osteoblasts respond to different implant materials. With this system, various agents can be applied to the osteoblast or the surface of the implant material can be modified to enhance osteoblast proliferation, differentiation and osseointegration. Increased osseointegration of implant prostheses will improve the lives and alleviate the suffering of many patients that are stricken with debilitating musculo-skeletal diseases.
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| Krause, A; Cowles, E A; Gronowicz, G (2000) Integrin-mediated signaling in osteoblasts on titanium implant materials. J Biomed Mater Res 52:738-47 |
| Cowles, E A; Brailey, L L; Gronowicz, G A (2000) Integrin-mediated signaling regulates AP-1 transcription factors and proliferation in osteoblasts. J Biomed Mater Res 52:725-37 |
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| Gronowicz, G; McCarthy, M B (1996) Response of human osteoblasts to implant materials: integrin-mediated adhesion. J Orthop Res 14:878-87 |
