Binder-Markey, DPT, PhD directs the Multiscale Neuromuscular Biomechanics Laboratory at Drexel University. The lab integrates physical therapy, basic science, and engineering principles through the use of experimental and computational modeling methods to better understand how changes in muscle properties following injury or disease affect physical function. The goal of this work is to develop new technologies and interventions that significantly improve patient care and outcomes. One focus of our work seeks to understand how skeletal muscle adapts following peripheral or central nervous system injuries and how combined muscle and nervous system changes affect upper limb function. Another focus of our work strives to understand the time course and causes of skeletal muscle wasting due to cancer driven cachexia and its effect on function and morbidity. This work has been funded by the Foundation for Physical Therapy Research, American Heart Association, The Brinson Foundation, and Shirley Ryan AbilityLab Catalyst Fund.
- Ishan Roy MD, PhD – Shirley Ryan Abilitylab
- Richard Lieber, PhD – Shirley Ryan Abilitylab, More Info
- Julius PA Dewarld, PT, PhD – Northwestern University, More Info
- Wendy Murray, PhD – Northwestern University, More Info
Develop rehabilitation tailored pre-clinical models of cancer associated cachexia to characterize mediators of physical and functional decline in cancer.
The primary objective this project seeks to determine the impact of cachexia on physical activity and function by developing a pre-clinical animal model of cancer that is optimized to study rehabilitation interventons. Given the multifactorial nature of functional change in cancer patients, animal studies permit the investigation of specific mechanisms linking cachexia and function. However, most cancer animal models are optimized for primary tumor pathology instead of longitudinal sequelae; as result, the few current models of cachexia use rare tumor phenotypes and rapidly succumb to primary tumor burden. Additionally, prior studies of these models of cachexia have not examined function with translationally significant depth or precision. Thus, the longitudinal sequence of pathophysiologic and functional changes linked to cachexia are undefined. This project seeks to determine this relationship by using a new approach that utilizes a model of cachexia optimized for longitudinal observations and measures of function innovative to cancer biology.
Quantification of biomechanical changes within muscle following stroke and affects function.
This project seeks to quantify the extent to which musculoskeletal structures of the hand change post stroke and how these changes affect function. Our initial results thus far have led to two unexpected findings. First, of 27 chronic stroke survivors studied who never received botulinum toxin (BTX), none showed any increases in the passive torques of their impaired hand. This is not what was hypothesized based on the clinical presentation of a substantially stiff hand fixed in a flexed wrist and hand resting posture in a majority of chronic stroke survivors. In contrast our second unexpected find was that all of the chronic stroke survivors studied who had received BTX injections showed marked increases in their passive muscle properties. These injections were used to treat undesirable increases of resistive torques from hyperactive muscles; however, it appears that these BTX injections have the opposite of the desired effect and potentially caused long-term increases in passive torques and decreases in passive range of motion. This was a most surprising finding that has important clinical implications for the future use of BTX.
We are currently working on using computational modeling, to determine if these increases in passive torques following BTX injections are significant enough to impair opening of the hand as compared to the muscle hyperactivity they were meant to prevent. Additionally, this work is being expanded to other joints of the body to see if these results are global or just hand and wrist specific.
Determining sources of passive biomechanical stiffness of within muscle.
This project seeks to determine how muscle structure contributes to passive mechanical properties of muscle. Collagen content is often used as a surrogate for connective tissue quantity to infer muscle stiffness and load bearing capacity. However, prior attempts to correlate passive mechanical properties with collagen content have not been successful. We found that this is likely a result of not accounting for the high variability in intramuscular connective tissue which causes collagen content to vary greatly between and within muscles. This collagen variability is driven primarily by dense connective tissue structures (i.e. internal tendon and fascial sheets) within the muscle. A consequence of these findings indicate that a single collagen content measurement, as often taken, does not accurately represent the muscle’s complex distribution of connective tissue and likely does not accurately reflect the load bearing capacity of a muscle. To further complicate the passive mechanics story, passive mechanical properties do not accurately scale from the sarcomere to the whole muscle level as is the case with active length-tension properties
Using computational modeling, we have set out to identify sources that could contribute to the non-linear scaling of passive fascicle mechanics to whole muscle mechancis. Thus far we have found that, to accurately model muscle passive mechanical properties, the model must reflect the complexity of the muscle. To a first approximation, architectural normalization helps, but in order to provide high resolution properties, additional terms including surrogate parameters for connective tissue content and muscle shear are needed. Though the precise structures that represent these mathematical surrogate terms are not currently clear and are the subject of ongoing investigations.