Traumatic Brain Injury: Linking Macro- to Micro-Biomechanics

Traumatic Brain Injury (TBI) is unique from any other neurological disorder or disease in that it is induced by a physical event. Supra-threshold traumatic loading may cause structural damage ranging from overt tissue disruption to extremely subtle, subcellular damage. Such physical damage may directly precipitate secondary pathophysiology in addition to providing the context in which negative intracellular cascades unfold. This underscores the need to accurately represent tissue- and cellular-level injury biomechanics to fully describe clinical TBI as well as to develop and validate experimental models.

Our Approach: To understand Mechanisms and Consequences Of Neural Cellular “Pathological Mechanosensation” in TBI

We determine injury tolerance criteria based on acute biophysical disruptions and evolving neurodegeneration

We apply a multi-level approach including in vitro (2-D/3-D cell culture) and in vivo (rodent and porcine) models

Multi Level analysis

Goal: understand cell/tissue biomechanics to establish links between physical and physiological consequences of TBI

3-D In Vitro Model of TBIin vitro

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Movies

Volumetric reconstruction of a 3-D neuronal-astrocytic co-culture

Volumetric reconstruction of a 3-D neuronal-astrocytic co-culture after injury

Caption: Cell death and network degeneration following high strain rate deformation.

In Vivo Model of TBI

alterations in membranes

Accordingly, a major objective of the Cullen Lab is to link macro- to micro- brain injury biomechanics with acute cellular damage and evolving neuropathology across various experimental models of TBI. We have developed a unique experimental framework to establish the relationships between defined cell- and tissue-level biomechanical inputs and acute structural/biophysical alterations that may be responsible for neural cell death or persistent dysfunction. Attention to the injury biomechanics is important for establishing links between the physical and physiological consequences of TBI, thus facilitating the development of targeted medical therapeutics to address the predominantly afflicted cell populations based on the mechanisms of injury. 

micro to macro

Contact Information

D. Kacy Cullen, Ph.D
105E Hayden Hall, 3320 Smith Walk
Philadelphia, PA 19104
dkacy@mail.med.upenn.edu

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News and Events

  • The Cullen Lab's research in TBI was featured in the Fall issue of Penn Medicine Magazine (p. 15-17). PDF
  • Dr. Cullen and colleague Dr. Douglas Smith were awarded a 3-year grant from the Department of Defense Joint Warfighter Medical Research Program to advance their work for "Repair of Segmental Nerve Defects Using Tissue-Engineered Nerve Grafts."
  • Dr. Cullen was invited to give a research talk at the Center for Translational Injury Research at the University of Texas Health Science Center in Houston, TX. He presented “Tissue Engineered Nerve Grafts for Peripheral and Central Nervous System Repair”.
  • The Cullen Lab was awarded a one-year pilot grant through the Penn Medicine Neuroscience Center to explore "Neuromodulation of Brain Circuits Using Transplantable Micro-Tissue Engineered Neural Networks."
  • James Harris, Ph.D., was awarded an NIH NRSA Postdoctoral Fellowship on the "Brain Injury Training Grant" through Penn's Center for Brain Injury & Repair. Dr. Harris' project is on "Mechanisms of Biophysical Responses and Neurodegeneration following Concomitant Blast and Inertial Traumatic Brain Injury."
  • Dr. Cullen gave a lecture at the American Society for Peripheral Nerve Annual Meeting in Kauai, Hawaii in January. The talk was titled "Tissue Engineered Grafts Accelerate Peripheral Nerve Repair By Direct Axon-Induced Axon Regeneration."
  • Laura Struzyna was a Poster Award Finalist at the Tissue Engineering and Regenerative Medicine International Society Annual Meeting in Atlanta, Georgia in November. Her poster was titled "Tissue Engineered Grafts Accelerate Peripheral Nerve Repair By Direct Axon-Induced Axon Regeneration."
  • Dr. Cullen gave an Invited Lecture at the Department of Biomedical Engineering at the Georgia Institute of Technology in May. He presented "Tissue Engineering Strategies to Restore Neural Circuitry and Create Living Scaffolds for Targeted Axonal Regeneration."
  • Dr. Cullen and collaborator Dr. Douglas Smith were awarded funding from the Department of Defense through the Rutgers - Cleveland Clinic Consortium of the Armed Forces Inst. of Regenerative Medicine. This project will investigate the efficacy of novel tissue engineered constructs encased in custom-built nerve guidance tubes to promote nerve regeneration following major peripheral nerve injury.
  • Bioengineering Ph.D. Candidate, Laura Struzyna, was selected for a prestigious 3-year Graduate Research Fellowship through the National Science Foundation based on her proposal for "Tissue Engineered Constructs for Neural Regeneration."

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