Blast-Induced Traumatic Brain Injury

Blast exposure is a 21st century reality in counter-insurgency warfare. The high incidence of closed head non-impact blast-induced traumatic brain injury (bTBI) in warfighters serving in Iraq and Afghanistan suggests a direct mechanism by which blast exposure detrimentally affects the brain. However, potentially unique injury mechanisms and exposure thresholds for bTBI remain unknown. The Cullen Lab is working to identify acute biophysical responses of neural cells occurring directly due to blast wave propagation through the brain. Relating these patterns of sub-cellular damage to both the predicted micro-injury biomechanics and later, evolving neuropathology may permit establishment of a “signature” of bTBI.

Neural Cellular Biophysical Responses to Blast Exposure

Damaged Neurons

caption: Blast-induced cellular damage (yellow) in the rat hippocampus


Damaged neurons (green) in the rat cortex following blast

Degenerating cortical neurons following blast exposure

caption: Degenerating neurons in the rat cortex following blast

Colorimetric Materials-Based Dosimetry Using Photonic Nanocrystals

To compliment these efforts, we have developed a novel materials-based blast injury dosimeter using photonic crystalline nanostructures that change color specifically following blast exposure. Appearing as an array of small colored stickers, these nanostructures may be affixed to uniforms and helmets to report blast exposure sufficient to induce even subtle neuropathology. Our current efforts focus on calibrating the degree of color change and/or color loss with blast levels inducing brain injury across a range of severities. This technology offers a lightweight, power-free sensor that can be readily interpreted by the naked eye, thus serving as an experimental tool as well as a diagnostics marker to improve bTBI outcomes in our warfighters. Collectively, our efforts to elucidate the causative mechanism(s) and potentially unique neuropathology of bTBI in parallel with blast dosimetry help establish exposure tolerances and facilitate the development of treatments to halt progressive neural damage and/or degeneration.

Colorimetric blast

BID concept and function

(A) BID arrays may be affixed to warfighter uniforms in multiple locations. These arrays consist of multiple engineered photonic crystalline microstructures, the colorimetric properties of which are a result of the nano-scale structure, creating so-called “structural color”. (B) We have previously demonstrated that blast exposure precisely disrupts the structure at the nano- and micro-scales, creating color change and loss, respectively (color change/loss scale bar: 1 mm; SEM scale bar: 500 nm). These properties make our photonic crystalline arrays ideal to serve as a colorimetric blast injury dosimeter.

Contact Information

D. Kacy Cullen, Ph.D
105E Hayden Hall, 3320 Smith Walk
Philadelphia, PA 19104

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News and Events

  • Dr. John O’Donnell, a postdoctoral fellow in the Cullen Lab, was awarded a prestigious NRSA (F32) Training Fellowship through the NIH. His project is titled “Modeling Disorders of Consciousness”. Way to go John!
  • The Cullen Lab and collaborators had a poster selected as one of the "Blue Ribbon Highlights" at the International Congress of Parkinson's Disease and Movement Disorders in Vancouver, Canada. The poster was titled “Tissue Engineered Nigrostriatal Pathway for Treatment of Parkinson’s Disease”. A write-up about the project in Neurology Today can be found here.
  • Dr. Cullen and collaborators received a major 4-year Merit Review Award from the Department of Veterans Affairs to advance their project “Transplantable Micro-Tissue Engineered Neural Networks to Restore the Nigrostriatal Pathway in Parkinson's Disease”. This exciting project applies cutting-edge tissue engineering and regenerative medicine techniques to build the full nigrostriatal pathway in vitro using human induced pluripotent stem cells, with efficacy testing of these human-scale constructs in a large animal model of Parkinson’s disease. Success of this project over the next several years will enable clinical trials based on precision medicine– rebuilding complex brain networks using a patients own cells and implanting these fully preformed constructs to replace vulnerable pathways lost due to neurodegenerative disease. The co-investigators on this project are Dr. Isaac Chen, Dr. John Wolf, and Dr. John Duda. Way to go team!
  • Dr. Cullen was promoted to Associate Professor at the University of Pennsylvania. Congratulations Dr. Cullen!
  • Congratulations to Laura Struzyna, a Bioengineering Doctoral Candidate in the Cullen Lab, whose winning entry for Penn's "Art in Science" competition was featured on the NIH Director's Blog!
  • The Cullen Lab and collaborators at Penn (Drs. Isaac Chen, Douglas Smith, and John Wolf) and Rutgers University (Drs. Joachim Kohn and Hilton Kaplan) were awarded a 3-year, $2.1 million dollar grant from the U.S. Dept. of Defense on "Tissue Engineering Strategies to Maintain Distal Target Efficacy and Promote Full Functional Recovery Following Major Peripheral Nerve Injury".
  • The Cullen Lab and collaborators had two abstracts selected as “Hot Topics” (top 2% of submissions) for presentation in a platform session at the World Parkinson’s Congress meeting in Portland, OR. Carolyn Keating, a Neuroscience doctoral candidate, presented "Diffuse Brain Injury in Swine Causes Plasmalemmal Dysruption and α-Synuclein Over-Expression in the Substantia Nigra". Dr. John Duda presented "Can Living Micro-Tissue Engineered Axonal Tracts Reconstruct the Nigrostriatal Pathway in PD?"
  • Dr. Cullen had the honor of being selected as one of "3 People to Watch in Neuroscience in 2016" by STAT News (Health, Medicine, and Biotech publication):
  • Congratulations to Laura Struzyna, a Bioengineering Doctoral Candidate in the Cullen Lab, who won second place in the Perelman School of Medicine 2016 "Art in Science" Competition. The winning image is shown here.
  • Penn and the Journal of Neural Engineering put out a press release for our most recent manuscript describing the Cullen Lab's novel micro-tissue engineered neural networks to restore brain circuitry. Link:
  • Carla Winter, and undergraduate researcher in the Cullen Lab for the past 3 years, was selected as a George J. Mitchell Scholar (one of only 12 in the U.S.): is very prestigious and well-deserved honor. Way to go Carla!
  • Dr. Cullen had the honor of giving a TED-style talk at Penn’s Annual Neuroscience Public Lecture Series on Neuroengineering: Where Biology Meets Technology. Dr. Cullen discussed the lab’s pioneering work on "Restoring Nervous System Structure and Function With Tissue Engineered 'Living Scaffolds'” (YouTube video:
  • 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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