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Sulfated Glycosaminoglycan Hydrogels for Treating Brain Volume Loss in TBI

Award Number: R56NS145513
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Sulfated Glycosaminoglycan Hydrogels for Treating Brain Volume Loss in TBI - PROJECT SUMMARY Moderate to severe traumatic brain injuries (msTBIs) cause significant brain volume loss and cavitation, which contributes to life-long disabilities and poor prognosis for a majority of msTBI patients. The brain extracellular matrix (ECM) is a meshwork of highly glycosylated proteins that provide structural and functional support to neural cells in the brain. Aberrant high mannose ECM N-glycosylation activates the lectin complement pathway and recruitment of inflammatory microglia. However, there are no effective treatments and the role of these factors in promoting brain volume loss in msTBI is unknown. There is a critical need to develop rationally designed, engineered brain tissue replacement technologies that can prevent brain volume and function losses post-msTBI. We previously developed a novel engineered chondroitin sulfate (eCS) glycomaterial and demonstrated that acutely implanted eCS matrices promoted subacute and chronic neuroprotection and functional vascular repair in msTBI lesions. Our preliminary findings reveal that the aberrant upregulation of high mannose N-glycans in msTBI lesions correlates with lectin complement and microglial activation, and that sulfation optimized CS oligomers can inhibit lectin complement activation and neuronal cytotoxity. Based on this evidence, we hypothesize that intracavitary implantation of rationally designed eCS matrix carrying sulfation optimized CS oligomers will mitigate complement pathway and microglial activation induced brain volume loss after msTBI. We propose to test this hypothesis in the following three specific aims: Aim 1- Determine lectin complement and microglia activation inhibiting effects of sulfation optimized CS oligomers in vitro; Aim 2- Elucidate microglial regulation of aberrant ECM remodeling in msTBI; and Aim 3 - Determine the effectiveness of sulfation optimized eCS matrix implants in mitigating chronic brain volume and functional losses after msTBI. Our published and preliminary findings provide a compelling basis for the development of a target specific and disease modifying regenerative immunomodulation therapy that can ameliorate aberrant ECM remodeling and brain volume loss in msTBI.


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 = $506,968 )
2026	2026	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/31/2026	NEW	$506,968
														Subtotal = $506,968

Grand Total All Awards = $506,968

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Sulfated Glycosaminoglycan Hydrogels for Treating Brain Volume Loss in TBI

Award Number: R56NS145513

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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