How localized biophysical cues (microchannels) in the pericellular niche influence 3D bone morphogenesis

Osteocytes and their extensive fluid-filled tunnel networks (lacuno-canalicular system) remain among the most sophisticated yet mysterious structures, capable of mechanotransduction and crucial for human skeletal health. However, current in vitro bone models often lack these networks, hindering studies on bone diseases such as age-related bone loss (osteoporosis) in the laboratory. Recently, Christian Gehre, PhD candidate in our lab at ETH Zurich, created a miniaturized in vitro bone model consisting of 3D bone cell networks. Using a two-photon laser microscope, he patterned a 3D grid of microchannels (down to 1 μm) within a photosensitized soft hydrogel. He then discovered that human mesenchymal stem cells sensed these micro-grid cues, self-organized into a 3D network within days, and committed to osteogenic differentiation. Thus, laser-guided formation of 3D networks from single cells at μm-scale resolution is demonstrated for the first time. In the future, we envisage the in vitro generation of bone organoid models comprising native-like osteocyte networks for both fundamental and translational research. Interested? Check it out:

Guiding bone cell network formation in 3D via photosensitized two-photon ablation, Acta Biomaterialia 2024. Christian Gehre, Wanwan Qiu, Patrick J?ger, Xiaopu Wang, Francisco Correia Marques , Brad Nelson , Ralph Mueller , Xiao-Hua Qin #Swiss National Science Foundation SNSF #ETH Zürich #Tissue Engineering #Bone #Osteocytes #3D Printing #Microtechnologies #3R