The surface of trabecular bone represents a distinct biomaterial interface where the hardest (bone) and softest (marrow) tissues co-exist while undergoing repeated remodeling via bone-resorbing osteoclasts and bone-forming osteoblasts. Accumulating data indicate that osteocytes beneath bone surface play a critical role in regulating the surface cell activities via secreting a set of soluble factors. However, investigating how surface and subsurface cells interact and regulate bone surface biology remains challenging due to anatomical inaccessibility of the inner surface of bone cavities and lengthy nature of bone remodeling. It is imperative to develop in vitro tissue models that can recapitulate bone tissue complexity and associated bone surface remodeling process. In this talk, I will introduce a new type of tissue-engineered trabecular bone model that represents both surface and subsurface cellular and extracellular complexity in a controlled and analytical manner. Mature bone consists of multiple layers of lamella bone, and bone is the best biomaterial to reproduce bone tissue biology. Having this mindset, we first developed a process to generate a thin section of demineralized bovine compact bone that supported the aligned adhesion of osteoblasts and structural mineral deposition. We then exploited tissue-engineering strategies to induce osteoblast-to-osteocyte differentiation via stacking multiple layers of osteoblasts pre-seeded demineralized bone paper and subsequently applying cyclic mechanical compression under hypoxic milieu. This additive manufacturing enabled control of the thickness of the trabecular bone tissue models with osteocytes. Finally, we demonstrated how subsurface osteocytes direct surface osteogenic and hematopoietic cellular activity in the context of chemical and mechanical stimulation. We envision that an established bone tissue model is expected to advance bioengineering trabecular bone for basic and applied researches significantly.

Engineering natural bone matrix to reproduce interface biology at bone and marrow

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.