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Timothy Miller, MD

Timothy A. Miller, MD, FACS
Professor Emeritus

Timothy Miller, MD

Dr. Miller's research focuses on bone tissue engineering at both molecular and tissue level. Using a well-known rabbit cranial defect model, his research team has tested a variety of different scaffolding materials and osteo-inductive agents for their ability to heal the defect in rabbits. They are working to develop a bone graft substitute (BGS) consist of PLGA scaffold, bone marrow stromal cells and recombinant BMP-2. While the BGS partially healed the defect, a large amount of BMP-2 is required. As widely acknowledged, the use of BMP-2 to repair large bony defects is cost prohibited.  Dr. Miller's laboratory is testing several alternatives to either replace BMP-2 with affordable small chemicals or enhance BMP-2 efficacy with naturally occurring peptides.

One such osteo-inductive molecule is oxysterol (derivatives of cholesterol). Oxysterol was first identified as an osteo-inductive molecule by our collaborator Dr. Paharmi at UCLA. Results suggest that oxysterol can synergize with recombinant BMP-2 to enhance bone formation in vitro. Oxysterol has also been found to be a potent stimulator of bone formation in 3-D PLGA scaffolds.

Currently, Dr. Miller and his research team working to delineate the molecular mechanism underlying synergistic effect of oxysterols and BMP-2. Preliminary results suggest the involvement of the MAP kinase pathway in mediating the synergy.

Oxysterol or oxysterol/BMP-2 is being tested in cellular scaffolds used to treat rabits with critical-sized cranial defect. The efficacy of this treatment will be assessed both histologically and biomechanically. The healing area will be analyzed by histomorphometry for bone formation. The stiffness of newly formed bone will be analyzed using a bending test. It is expected that tissue engineered PLGA scaffods treated with oxysterol and BMP-2 can heal a critical-sized cranial defect in rabbit by using much smaller amount of BMP-2.

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Phone: (310) 825-5510

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