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Injectable hydrogels for hiPSC-neuron therapy of spinal cord injury

Award Number: K01EB033870
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/14/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Injectable hydrogels for hiPSC-neuron therapy of spinal cord injury - Regenerative medicine cell transplantation strategies are limited by poor transplanted cell survival, retention, and integration. To overcome this, I propose development of an engineered biomaterial that addresses two major causes of transplanted cell death: (i) acute membrane damage during injection and (ii) long-term exposure to a toxic microenvironment, by providing (i) cell encapsulation within an injectable hydrogel and (ii) slow-release of growth factors. To evaluate the preclinical effectiveness of this biomaterial, I will target cervical spinal cord injury (SCI), which results in permanent sensorimotor dysfunction and has no clinically available regenerative therapies. My data demonstrates that transplanting human induced pluripotent stem cell-derived neurons (hiPSC-neurons) significantly improves anatomical and functional outcomes in rat models of cervical SCI; however, this cell type suffers from poor transplanted cell viability, reducing therapeutic efficacy. I have already shown that use of an injectable hydrogel significantly improves the acute viability of encapsulated cells by providing mechanical shielding during injection, which resulted in statistically improved neurite outgrowth and forelimb function. I now hypothesize that tuning the temporal growth factor-release properties of this designer, injectable hydrogel will significantly improve long-term survival of transplanted hiPSC-neurons, leading to significantly improved anatomical and functional outcomes. Specifically, in Aim 1, I will optimize a growth factorrelease system in vitro to assist hiPSC-neurons in surviving oxidative stress and excitotoxicity that are present at the injury site. In Aim 2, I perform functional evaluation of this biomaterial/cell therapy in a subacute model of SCI in comparison to standard delivery vehicles (saline and fibrinogen) and appropriate controls. My career goal is to lead a translational laboratory that leverages expertise in biomaterials and stem cell biology to develop regenerative therapies for central nervous system (CNS) injury. This Career Development Award would enable me to enhance my strong background in CNS neurodegeneration and stem cell biology with new expertise in biomaterial design and translational bioengineering. My career development plan includes (1) formal coursework in materials science and bioengineering, (2) technical training in recombinant biomaterials synthesis and characterization, (3) close mentorship by an outstanding bioengineer with a strong track-record of successful training and collaboration, and (4) career guidance by an Advisory Committee to prepare for my transition to independence. My training plan leverages the outstanding resources available within Stanford University and national and international events to strengthen my scientific network, build on my extensive mentorship and grantsmanship skills, and polish my scientific communication. This plan will position me to submit innovative and interdisciplinary application packets for tenure-track Assistant Professorships in my last year of this award as I embark on an independent career at the intersection of biomaterials science and CNS regeneration.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $168,296 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	5/25/2026	NON-COMPETING CONTINUATION	$168,296
														Subtotal = $168,296

Issue Date FY: 2025 ( Subtotal = $168,296 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	4/16/2025	NON-COMPETING CONTINUATION	$168,296
														Subtotal = $168,296

Issue Date FY: 2024 ( Subtotal = $168,296 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	6/14/2024	NEW	$168,296
														Subtotal = $168,296

Grand Total All Awards = $504,888

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Injectable hydrogels for hiPSC-neuron therapy of spinal cord injury

Award Number: K01EB033870

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/14/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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