Neural Tissue Engineering

Nerve repair is a greatly needed medical advance for individuals who have undergone traumatic injuries or nerve atrophy due to disease.  My research interests focus on how to improve nerve regrowth and regeneration.  We utilize a multidisciplinary approach that combines biology, materials, and analytical chemistry techniques to bioengineer new methods for nerve growth.

Stacked z-series of tri-color immunostaining of two adjacent dorsal root ganglion neurons within a 3D collagen I scaffold (1.5 mg/ml, acquired on 100x oil objective, 20 µm scalebar, Jason Papke).

We use isolated peripheral nerve cells and model nerve cell lines to regenerate and regrow on 2 dimensional surfaces and within 3 dimensional scaffolds of naturally occuring materials as well as synthetic materials.  We use chemical growth factors and electrical stimulation to change the microenvironment of regrowing nerves.

Dorsal root ganglion isolated neurons stained with neurofilament 3A10 antibody and grown on 3D collagen gels.  (100 µm scalebar, Mallory Smyth).

As nerves regrow, it is important to determine that they have reinnervated target tissues appropriately.  Therefore, we combine analytical chemistry techniques such as amperometry to detect synaptic communication from the nerve cells.

 

Amperometric recording from a sympathetic neuron growing on a 2D substrate of collagen.  The neuron was stimulated to release catecholamin neurotransmitter with nicotine (100 µM) application at the time of the arrow for the duration of the recording.  Individual spikes are analyzed for quantal content and kinetics of release (Jason Papke).

We can utilize RNAi to target specific synaptic proteins for knockdown of protein expression. These combined techniques provide a powerful set of tools to determine the chemical, structural, and electrical microenvironment that will permit nerve regeneration and appropriate reinnervation.

Laminin coats a 1 mg/ml collagen scaffold.  Collagen was imaged with internal reflection, and laminin was fluorescently labeled with a 594 fluorophore.  Scale = 50 µm.  (Josh Hammer and Jason Papke).

From these results a molecular model can be engineered within 3D scaffolds for improved capabilities to regenerate nerves in the body.

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