Sundar Srinivasan, Ph.D.
Department of Orthopaedics and Sports Medicine (Orthopaedic Sciences Lab)
"Simulation and Non-Empirical Control of Bone Adaptation to Mechanical Stimuli"


ABSTRACT

The skeleton’s response to physical exercise displays numerous hallmarks of complex adaptive
systems.  For instance, bone response to physical stimuli is often time counterintuitive and occurs
at paradoxical sites within the skeleton.  As well, even brief mechanical stimuli (order of 100 s)
have been shown to induce adaptive responses in bone that last for days and weeks.  To explore
the complexity of bone’s response to physical stimuli, we have initiated studies that attempt for
the first time, to explore bone adaptation as an emergent or bottom-up process.  In this context,
using the technique of agent based modeling, we have developed a model that simulates the
response of bone cells (Ca2+ ion signaling) during application of mechanical stimuli – i.e., in
the real-time and on the order of seconds.  We have also examined the adaptive consequence of
real-time Ca2+ signaling in cells upon bone tissue adaptation that arises down-stream.  We find
that upon appropriate “training”, our model is capable of accurately simulating bone formation
induced in vivo over the course of 3-weeks by a variety of loading protocols.  Importantly, in
preliminary experiments, we find that our model is also capable of forecasting or predicting
response to extrapolative mechanical loading protocols not used to ‘train’ the model.  While the
model remains to be more extensively validated, it provides the first predictive tool that can be
utilized to design potent mechanical loading protocols to optimally enhance adaptation in bone.

In the seminar, I will attempt to describe our modeling approach to exploring bone adaptation.
While this will be the focus of the seminar, I will provide a brief introduction to bone biology,
our experimental data and to the technique of agent based modeling and its utility.  I expect to
conclude the seminar with a brief overview of where we are going with this kind of a decentralized,
bottom-up approach to exploring bone biology.