TISSUE ENGINEERING & REGENERATIVE MEDICINE: Reconstructing the Nervous System Following Neurotrauma or Neurodegenerative Disease
The Cullen Lab's objective in tissue engineering and regenerative medicine is to build anatomically- and developmentally-inspired living tissue to mitigate trauma-induced deficits or augment the body’s capacity for regeneration. Here, focus is given to novel biofabrication strategies for tissue engineered brain pathways to restore the connectome and "living scaffolds" for neuroregeneration.
Tissue Engineered Brain Pathways to Restore the Connectome
Tissue Engineered "Living Scaffolds" to Promote Axon Regeneration following Peripheral Nerve Injury (PNI) or Spinal Cord Injury (SCI)
Tissue Engineered "Living Scaffolds" for Sustained Neuronal Replacement following Traumatic Brain Injury or Neurodegenerative Disease
Pre-Innervated Tissue Engineered Muscle for Neuromuscular Reconstruction
NEURAL ENGINEERING: Tissue Engineered Neuroelectrical-Optical Paradigms for Brain-Machine Interface and Biologically-Based Neuromodulation
In the arena of Neural Engineering, the objective is to leverage neural tissue engineering strategies to develop "biohybrid" neuroprosthetic interfaces, enable synaptically-based neuromodulation using biological constructs, and provide optical control of neural circuitry.
"Living Electrodes" for Neuroprosthetic Interface and Synaptic-Based Neuromodulation
⇒Engineered Axonal Tracts as “Living Electrodes” for Synaptic-Based Modulation of Neural Circuitry, Advanced Functional Materials Sept 14: 1701183 (2017)
Biohybrid Neural Interface Microsystems as Anatomically- and Physiologically-Relevant Testbeds
⇒Assessing Functional Connectivity Across Three-Dimensional Tissue Engineered Axonal Tracts Using Calcium Fluorescence Imaging, J Neural Engin 15(5):056008 (2018)
⇒Neural Tissue Engineering and Biohybridized Microsystems for Neurobiological Investigation In Vitro (Part 1), Critical Reviews in Biomedical Engineering 39(3):201-240 (2011)
NEUROTRAUMA: Traumatic Brain Injury (TBI) & Neurodegeneration
The focus of the Cullen Lab’s research in neurotrauma is the application of engineering principles to better understand the causative mechanisms and pathophysiological responses following traumatic injury to the nervous system. Specific attention is given to neural injury biomechanics and mechanisms of acute biophysical cellular/tissue damage.
Linking Macro-to-Micro Biomechanics
⇒Neurons in Subcortical Oculomotor Regions are Vulnerable to Plasma Membrane Damage after Repetitive Diffuse Traumatic Brain Injury in Swine, J Neurotrauma Feb 5 (2020).
⇒A Porcine Model of Traumatic Brain Injury Via Head Rotational Acceleration, Injury Models of Central Nervous System: Traumatic Brain Injury, Methods in Molecular Biology 1462:289-324. Dixon, Kobeissy, Hayes and Mondello eds (2016)
Functional Consequences of TBI
⇒Challenges and Demand for Modeling Disorders of Consciousness following Traumatic Brain Injury, Neuroscience & Biobehavioral Reviews Mar;98:336-346 (2019)
TBI-Induced Neurodegeneration & Neuroinflammation