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.