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
⇒Emerging Regenerative Medicine and Tissue Engineering Strategies for Parkinson’s Disease, npj Parkinson’s Disease Jan 8; 6:4 (2020)
⇒Bundled Three-Dimensional Human Axon Tracts Derived from Cerebral Organoids, iScience Nov 22; 21:57-67 (2019)
⇒Tissue Engineered Nigrostriatal Pathway for Treatment of Parkinson’s Disease, J Tissue Engin & Regen Med 12(7): 1702-1716 (2018)
⇒Rebuilding Brain Circuitry with Living Micro-Tissue Engineered Neural Networks, Tissue Engin Part A 21(21-22): 2744-56 (2015)
Tissue Engineered "Living Scaffolds" to Promote Axon Regeneration following Peripheral Nerve Injury (PNI) or Spinal Cord Injury (SCI)
⇒Tissue Engineered Axon Tracts Serve as Living Scaffolds to Accelerate Axonal Regeneration and Functional Recovery Following Peripheral Nerve Injury in Rats [bioRxiv 654723 (2019)].
⇒Peripheral Nerve Repair Using Tissue Engineered “Living Scaffolds” Comprised of Stretch-Grown Axonal Tracts Promotes Survival of Spinal Cord Motor Neurons [bioRxiv 847988 (2019)]
⇒“Stretch-Growth” of Motor Axons in Custom Mechanobioreactors to Generate Long-Projecting Axonal Constructs, J Tissue Engin & Regen Med Nov; 13(11):2040-2054 (2019)
Tissue Engineered "Living Scaffolds" for Sustained Neuronal Replacement following Traumatic Brain Injury or Neurodegenerative Disease
⇒A Tissue-Engineered Rostral Migratory Stream for Directed Neuronal Replacement. Neural Regen Res 13(8):1327-1331 (2018)
⇒Three-Dimensional Tissue Engineered Aligned Astrocyte Networks to Recapitulate Developmental Mechanisms and Facilitate Nervous System Regeneration, J Vis Exp Jan 10:131 (2018)
⇒Mechanical Elongation of Astrocyte Processes to Create Living Scaffolds for Nervous System Regeneration, J Tissue Engin & Regen Med June 7 (2016)
Pre-Innervated Tissue Engineered Muscle for Neuromuscular Reconstruction
⇒Innervated Tissue Engineered Muscle for Neuromuscular Reconstruction Following Volumetric Muscle Loss [bioRxiv 840124 (2019)]
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
⇒Optically-Controlled "Living Electrodes" with Long-Projecting Axon Tracts for a Synaptic Brain-Machine Interface [bioRxiv 333526 (2018)]
⇒Bioactive Neuroelectronic Interfaces, Frontiers in Neuroscience, section Neuroprosthetics, March 29; 13:269 (2019)
⇒Engineered Axonal Tracts as “Living Electrodes” for Synaptic-Based Modulation of Neural Circuitry, Advanced Functional Materials Sept 14: 1701183 (2017)
⇒Bionic Connections: Living Bridges to Connect Bionic Limbs to the Nervous System. Scientific American 308(1): 52-57 (2013)
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)
⇒Anatomically-Inspired Three-Dimensional Micro-Tissue Engineered Neural Networks for Nervous System Reconstruction, Modulation, and Modeling, J Vis Exp May 31:123 (2017)
⇒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)
⇒Trauma-Induced Plasmalemma Disruptions in 3-D Neural Cultures are Dependent on Strain Modality and Rate, J Neurotrauma 28(11): 2219-33 (2011)
Functional Consequences of TBI
⇒Challenges and Demand for Modeling Disorders of Consciousness following Traumatic Brain Injury, Neuroscience & Biobehavioral Reviews Mar;98:336-346 (2019)
⇒Concussion Induces Hippocampal Circuitry Disruption in Swine, J Neurotrauma Jul 15:34(14): 2303-14 (2017)
⇒Blast-Induced Color Change in Photonic Crystals Corresponds with Brain Pathology, J Neurotrauma 28(11): 2307-18 (2011).
⇒Color Changing Photonic Crystals Detect Blast Exposure, NeuroImage 54S1:S37-S44 (2010).
TBI-Induced Neurodegeneration & Neuroinflammation
⇒Mossy Cell Hypertrophy and Synaptic Changes in the Hilus Following Mild Diffuse Brain Injury in Pigs, J Neuroinflammation 17(1), 44 (2020)
⇒Acute Drivers of Neuroinflammation in Traumatic Brain Injury, Neural Regeneration Research 14(9):1481-1489 (2019)
⇒Rapid Neuroinflammatory Response Localized to Injured Neurons After Diffuse Traumatic Brain Injury in Swine, Experimental Neurology 290:85-94 (2017)