Yongkuk Park 1, Tadatoshi Sato 2 & Jungwoo Lee 1,3,4,*
1Department of Chemical Engineering, Institute for Applied Life Sciences, University of Massachusetts, Amherst, MA 01003, USA.
2Department of Medicine, UMass Chan Medical School, Worcester, MA 01605, USA.
3Department of Biomedical Engineering, University of Massachusetts, Amherst, MA 01003, USA.
4Molecular & Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA 01003, USA.
*Corresponding author: correspondence to Jungwoo Lee
Osteoclasts are the primary target for osteoporosis drug development. Recent animal studies revealed the crucial roles of osteoblasts in regulating osteoclastogenesis and the longer lifespans of osteoclasts than previously thought with fission and recycling. However, existing culture platforms are limited to replicating these newly identified cellular processes. We report a demineralized bone paper (DBP)-based osteoblast culture and osteoclast assay platform that replicates osteoclast fusion, fission, resorption, and apoptosis with high fidelity and analytical power. An osteoid-inspired DBP supports rapid and structural mineral deposition by osteoblasts. Coculture osteoblasts and bone marrow monocytes under biochemical stimulation recapitulate osteoclast differentiation and function. The DBP-based bone model allows longitudinal quantitative fluorescent monitoring of osteoclast responses to bisphosphonate drug, substantiating significantly reducing their number and lifespan. Finally, we demonstrate the feasibility of humanizing the bone model. The DBP-based osteo assay platforms are expected to advance bone remodeling-targeting drug development with improved prediction of clinical outcomes.