Unraveling Calcium Dynamics and Immune Interactions in Bone Graft Substitute Environments through Advanced Ratiometric Imaging

The indispensable role of the skeletal system in enabling motion and providing structural support to vital organs underscores the imperative for efficacious interventions in the context of substantial bone defects. Notably, Bone Graft Substitutes (BGS) have emerged as a viable therapeutic avenue, exhibiting success in promoting bone formation through their inherent osteoinductive potential. Despite the considerable promise associated with BGSs, the intricate mechanisms governing material-induced osteoinduction remain elusive. Bohner et al. have recently proposed a novel mechanism termed Sustained Local Ionic Homeostatic Imbalance (SLIHI) as a potential instigator of material-induced osteoinduction. The hypothesis posits that localized depletion of calcium and phosphate during the calcification process may lead to SLIHI, thereby modulating inflammation and instigating an osteoinductive response. Calcium signaling is pivotal in diverse biological and cellular processes, with a particular impact on skeleton mineralization. The continuous remodeling of the skeleton, involving bone resorption and new bone deposition, results in fluctuating extracellular calcium levels corresponding to different phases of remodeling. To comprehensively explore SLIHI, it becomes imperative to scrutinize the spatial distribution and concentration of calcium. This investigation can be effectively conducted through quantitative imaging techniques utilizing calcium-sensitive ratiometric probes. Ratiometric imaging is a scientific approach that utilizes specialized probes to assess variations in calcium concentrations outside cells quantitatively. This technique relies on the simultaneous acquisition of signals at two distinct wavelengths, allowing for the calculation of a ratio that is sensitive to changes in extracellular calcium levels. Here, we aim to assess the impact of ion-regulating BGS on extracellular calcium concentrations and the concurrent influence on adjacent immune cells.

The indispensable role of the skeletal system in enabling motion and providing structural support to vital organs underscores the imperative for efficacious interventions in the context of substantial bone defects. Notably, Bone Graft Substitutes (BGS) have emerged as a viable therapeutic avenue, exhibiting success in promoting bone formation through their inherent osteoinductive potential. Despite the considerable promise associated with BGSs, the intricate mechanisms governing material-induced osteoinduction remain elusive. Bohner et al. have recently proposed a novel mechanism termed Sustained Local Ionic Homeostatic Imbalance (SLIHI) as a potential instigator of material-induced osteoinduction. The hypothesis posits that localized depletion of calcium and phosphate during the calcification process may lead to SLIHI, thereby modulating inflammation and instigating an osteoinductive response.


Calcium signaling is pivotal in diverse biological and cellular processes, with a particular impact on skeleton mineralization. The continuous remodeling of the skeleton, involving bone resorption and new bone deposition, results in fluctuating extracellular calcium levels corresponding to different phases of remodeling. To comprehensively explore SLIHI, it becomes imperative to scrutinize the spatial distribution and concentration of calcium. This investigation can be effectively conducted through quantitative imaging techniques utilizing calcium-sensitive ratiometric probes.


Ratiometric imaging is a scientific approach that utilizes specialized probes to assess variations in calcium concentrations outside cells quantitatively. This technique relies on the simultaneous acquisition of signals at two distinct wavelengths, allowing for the calculation of a ratio that is sensitive to changes in extracellular calcium levels. Here, we aim to assess the impact of ion-regulating BGS on extracellular calcium concentrations and the concurrent influence on adjacent immune cells.

This project seeks to implement ratiometric imaging both in controlled laboratory conditions (in vitro) and within living organisms (in vivo) to examine how bone graft substitutes influence extracellular calcium levels and interact with immune cells. The ultimate goal is to enhance our understanding of these processes to optimize osteoinduction. Candidates with prior familiarity with cell culture and microscopy will be preferably considered. The project goals could be tailored to the student`s interests, expertise, and project requirements.

This project seeks to implement ratiometric imaging both in controlled laboratory conditions (in vitro) and within living organisms (in vivo) to examine how bone graft substitutes influence extracellular calcium levels and interact with immune cells. The ultimate goal is to enhance our understanding of these processes to optimize osteoinduction.

Candidates with prior familiarity with cell culture and microscopy will be preferably considered. The project goals could be tailored to the student`s interests, expertise, and project requirements.

Dr. Stefanie S. Wissmann, Postdoc (email:stefanie.wissmann@hest.ethz.ch), ETH Zürich / Laboratory for Bone Biomechanics (https://www.bone.ethz.ch/) For application, please provide your CV and transcripts of B.Sc. and M.Sc.

Dr. Stefanie S. Wissmann, Postdoc (email:stefanie.wissmann@hest.ethz.ch), ETH Zürich / Laboratory for Bone Biomechanics (https://www.bone.ethz.ch/) For application, please provide your CV and transcripts of B.Sc. and M.Sc.