Approximately 1.2 million Americans have sustained some form of spinal cord injury (SCI), with an estimated annual economic impact of $20 billion. Our overarching vision is to use a multimodality approach to promote axon regeneration and improve behavioral outcomes in the most challenging and clinically predictive SCI model, complete spinal transection. We will optimize and reduce to practicality bioengineered, template agarose guidance scaffolds for axonal regeneration based on substantial experience from a collaborative, multi-PI effort that pairs leaders in bioengineering at Michigan State University with a top national laboratory in the field of SCI research at UC San Diego.
Specific Aim 1 : Optimize Templated Agarose Scaffold Design Optimize scaffold design by adding: a)drug delivery capabilities using layer by layer (LBL) technology to control release of growth factors, and b) biodegradability properties by integration of hydrogels or agarose/polyelectrolyte composites.
Specific Aim 2 : UseTemplated Agarose Scaffolds to Promote Host Axonal Regeneration After T3 Complete Spinal Cord Injury Aim 2 will use optimized scaffolds from Aim 1 to enhance axonal growth into and beyond SCI lesions in vivo. Success in this model can lead to clinical translation.
Specific Aim 3 : Use Templated Agarose Scaffolds to Promote Formation of Neuronal Relay Circuits After T3 Complete Spinal Cord Injury Aim 3 will combine two cutting edge technologies - bioengineered scaffolds and stem cells - to formulate a new generation of therapies that could constitute the most promising approach yet for treating SCI. The natural progression of this work can lead to translation to our non-human primate model of SCI, and then to clinical trials.

Public Health Relevance

Approximately 1.2 million Americans have sustained some form of spinal cord injury (SCI), with an estimated annual economic impact of $20 billion.SCI tragically disables its victims and extracts a psychological toll on patients and caregivers. This project incorporates material science, drug delivery, tissue engineering, stem cell biology and neurosciences to promote axon regeneration and improve behavioral outcomesafter SCI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB014986-01
Application #
8276806
Study Section
Neurotechnology Study Section (NT)
Program Officer
Hunziker, Rosemarie
Project Start
2012-05-15
Project End
2017-04-30
Budget Start
2012-05-15
Budget End
2013-04-30
Support Year
1
Fiscal Year
2012
Total Cost
$531,487
Indirect Cost
$131,174
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Lu, Paul; Woodruff, Grace; Wang, Yaozhi et al. (2014) Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury. Neuron 83:789-96
Lynam, Daniel; Peterson, Chelsea; Maloney, Ryan et al. (2014) Augmenting protein release from layer-by-layer functionalized agarose hydrogels. Carbohydr Polym 103:377-84
Gao, Mingyong; Lu, Paul; Bednark, Bridget et al. (2013) Templated agarose scaffolds for the support of motor axon regeneration into sites of complete spinal cord transection. Biomaterials 34:1529-36