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




























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

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News and Events

  • The Cullen Lab and collaborators Dr. John Wolf, Dr. Misha Serruya, Dr. Brain Litt, Dr. Reuben Kraft and Dr. Isaac Chen were awarded a 3-year, $2 million dollar cooperative agreement (U01) from the NIH to further pioneer "Biological 'Living Electrodes' Using Tissue Engineered Axonal Tracts to Probe and Modulate the CNS".
  • The Cullen Lab received a 2-year grant from the U.S. Dept. of Defense to advance "Novel Tissue-Engineered Nerve Grafts for Repair of Currently Untreatable Peripheral Nerve Injury".
  • Bioengineering Ph.D. Candidate, Kritika Katiyar, was selected for a prestigious NRSA F31 Graduate Research Fellowship through the National Institutes of Health based on her proposal for "Molecular Mediators of Axon-Facilitated Axon Regeneration."
  • Dayo Adewole, a Bioengineering Ph.D. student in the Cullen Lab, was awarded a 3-year Graduate Research Fellowship through the National Science Foundation to develop next-generation neuroprosthetic interfaces. Way to go Dayo!
  • The Cullen Lab and collaborators Dr. John Duda, Dr. Isaac Chen, and Dr. John Wolf were awarded a 2-year grant from the Michael J. Fox Foundation for the project "Restoring the Nigrostriatal Pathway with Living Micro-Tissue Engineered Axonal Tracts".

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