(588f) Tissue-Engineered Trabecular Bone Model Using Demineralized Bone Slices

The trabecular bone is a multi-functional dynamic tissue that maintains mechanical, mineral, and blood homeostasis in response to continually changing external physical stress and internal physiological need, respectively. The complexity of trabecular bone tissue has been increasingly classified mainly using mouse models, but in vitro reconstitution of trabecular bone tissue complexity and metabolism has remained challenging due to the lack of relevant experimental models. Remodeling sites collectively cover about 5% of the trabecular bone surface at any time, and the rest surface remains quiescence. Bone-forming osteoblasts and bone-resorbing osteoclasts drive the bone remodeling process. Accumulating data indicate that osteocytes, the primary mechanosensory cells residing beneath of the lamella bone play a central role in regulating the bone surface metabolic activity via secreting a set of soluble factors. In this talk, I will describe our on-going effort to create in vitro functional trabecular bone tissue models that represent both cellular and extracellular complexity in a controlled and analytical manner.

Many investigators believe that bone is probably the best biomaterial for creating bone tissue. We developed a method to process a compact bovine bone into demineralized thin slices (20µm). We hypothesize that multiple layering osteoblast pre-seeded demineralized bone slices will reproduce the lamellar structure of bone tissue complexity. Demineralized bovine bone slices support osteoblast differentiation, further maturation into osteocytes, and osteoclasts. When osteoblasts pre-seeded demineralized bone slices are stacked and exposed to cyclic compression under hypoxic milieu, they differentiate into osteocytes and reproduce both surface and subsurface trabecular bone tissue complexity. The prepared resting state of trabecular bone model is chemically stimulated when exposed to vitamin D3 and prostaglandin E2 with the substantial shift of bone remodeling cytokine profiles such as OPG and RANKL. We envision that our tissue-engineered trabecular bone models with demineralized bone paper will allow understanding various aspects of trabecular bone biology and harnessing their intrinsic functions for clinical applications.