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.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Study Section
Neurotechnology Study Section (NT)
Program Officer
Hunziker, Rosemarie
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Kumamaru, Hiromi; Lu, Paul; Rosenzweig, Ephron S et al. (2018) Activation of Intrinsic Growth State Enhances Host Axonal Regeneration into Neural Progenitor Cell Grafts. Stem Cell Reports 11:861-868
Lu, Paul; Ceto, Steven; Wang, Yaozhi et al. (2017) Prolonged human neural stem cell maturation supports recovery in injured rodent CNS. J Clin Invest 127:3287-3299
Shahriari, Dena; Koffler, Jacob Y; Tuszynski, Mark H et al. (2017) Hierarchically Ordered Porous and High-Volume Polycaprolactone Microchannel Scaffolds Enhanced Axon Growth in Transected Spinal Cords. Tissue Eng Part A 23:415-425
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Shahriari, Dena; Koffler, Jacob; Lynam, Daniel A et al. (2016) Characterizing the degradation of alginate hydrogel for use in multilumen scaffolds for spinal cord repair. J Biomed Mater Res A 104:611-619
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van Niekerk, Erna A; Tuszynski, Mark H; Lu, Paul et al. (2016) Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury. Mol Cell Proteomics 15:394-408
Kadoya, Ken; Lu, Paul; Nguyen, Kenny et al. (2016) Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Nat Med 22:479-87
Lee-Kubli, Corinne A; Ingves, Martin; Henry, Kenneth W et al. (2016) Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury. Exp Neurol 278:91-104
Gao, Mingyong; Lu, Paul; Lynam, Dan et al. (2016) BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration. J Neural Eng 13:066011

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