(445e) Recapitulation of Bone Surface Tissue Complexity and Remodeling on Demineralized Bone Paper

It has been well documented that trabecular bone undergoes repeated surface remodeling under tight molecular regulation. However, how regulatory molecules form spatiotemporal profiles and direct bone remodeling cellular processes within trabecular bone cavities remains uncertain due to lack of relevant experimental models. Here, we report a new strategy to create tissue engineered in vitro bone tissue model that reproduces essential bone tissue complexity and physiological processes with high fidelity and control. An osteoid resembling demineralized bone paper supported osteoblasts to develop mineralized mature bone tissue and subsequently acquire a resting state bone lining cell phenotype. Vitamin D3 and prostaglandin E2 stimulation reverted lining cells to osteoblasts. Shifted regulatory molecular profiles induced differentiation of bone marrow mononuclear cells into osteoclasts. By layering stimulated osteoblasts above resting lining cells using demineralized bone paper insert with a spacer, we simulated a local activation of trabecular bone niche with defined spatiotemporal molecular gradients. Quantitative spatial mapping of bone remodeling activity substantiated that osteogenic cells forming extensive gap junctions are significantly less responsive to stimulative molecules than bone marrow mononuclear cells that function as individual cells. These findings deliver new insights into molecular and cellular regulation of trabecular bone remodeling, and the established model may enable to study various aspects of bone biology on endosteal niche.