Osteocyte Mechanobiology

Osteocytes are mechanosensory cells embedded in the bone matrix. They sense mechanical forces from either the extracellular matrix (ECM) or the interstitial fluid flow within bone cavities via a variety of mechanosensors. In this project, we create bioengineered 3D bone cell models to study how osteocytes perceive and respond to different mechanical properties of their microenvironments as well as biophysical stimuli applied. Since bone in vivo is a mechanically active tissue, additional improvement of such static bone models could be achieved by including mechanical stimulation. Compression at the tissue level leads to matrix deformation, fluid flow through displacement within the matrix as well as hydrostatic pressure, all of which can be sensed by the resident cells. We, therefore, are interested in studying immediate cell responses as well as long-term effects of fluid shear stress and cyclic compressive loading on bone formation in vitro. We exploit Ca²⁺-imaging to analyze transient biochemical signals in living osteocytes stimulated by fluidic shear stress (see GIF) and are investigating down-stream effects of mechanical stimulation with respect to osteogenic differentiation and tissue maturation.

Insights into the mechano-regulated bone tissue maturation will be further utilized in an endeavor to integrate our bioengineered bone models with other musculoskeletal tissues in vitro. As part of the ETH Zurich Advanced Engineering with Living Materials ǀ ALIVE initiative, we aim to develop a miniaturized human joint-on-chip that may eventually enable researchers to study the role of mechanical forces in joint development in the laboratory with minimal reliance on animal experimentation.

Collaborators:

• Hao Liu and Prof. Marcy Zenobi-Wong, Tissue Engineering and Biofabrication, ETH Zurich
• Ali Kalkan and Prof. Ori Bar-Nur, Laboratory of Regenerative and Movement Biology, ETH Zurich
• Rodrigo Castillo-Acuña and Prof. Dennis Kochmann, Mechanics and Materials Laboratory, ETH Zurich
  

Related student project:

Margherita Bernero (FS 2021, Master Thesis, D-ITET)