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Anti-microbial platelet-like-particles to treat internal bleeding and augment subsequent healing

Award Number: R01HL162809
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Anti-microbial platelet-like-particles to treat internal bleeding and augment subsequent healing - PROJECT SUMMARY Uncontrolled bleeding following trauma represents a significant clinical problem; exsanguination is the major cause of death in both civilian and battlefield traumas. If hemostasis is achieved, wound repair following trauma can be impeded by several complications including infection, keloid formation, insufficient blood flow and a compromised immune system. Traumatic brain injury (TBI) also frequently occurs concurrently with hemorrhage following trauma and is associated with high risks of infection. Infections are a leading cause of mortality, morbidity, and economic disruption around the world, highlighting the need for better methods to achieve hemostasis and improve wound healing following trauma. Clot formation is critical to the cessation of bleeding and involves the formation of a platelet plug embedded within a fibrin mesh. Platelets bind multiple fibrin fibers and actively apply forces to contract the network, thereby stabilizing the developing clot. Furthermore, platelet- mediated clot contraction is thought to augment wound healing following cessation of bleeding by reestablishing blood flow to downstream tissues and by providing mechanical stimulation to surrounding cells. We have recently developed platelet-like particles (PLPs) created from highly deformable microgels (gels) conjugated to wound- targeting motifs, which specifically target wound environments through high affinity binding to the provisional matrix protein fibrin. Our prior studies demonstrate that PLPs recapitulate a number of functions of natural platelets, including augmentation of clotting of adult plasma in vitro, decreased bleeding times in rodent models of traumatic injury, specific homing to injury sites, induction of clot contraction, and enhancement of wound repair in rodent models of dermal injury. We have also shown in a rodent model of TBI that PLPs decrease blood brain barrier (BBB) permeability and neuroinflammation after injury. The long-term goal of this project is to develop intravenous hemostatic PLPs that are triggered by the body’s native clotting cascade to promote clotting and, following hemostasis, augment wound healing. Our central hypothesis is that the combination of PLP-mediated clot contraction and delivery of antimicrobial nanosilver will significantly improve wound healing following traumatic injury by providing mechanical stimulation to surrounding cells and by preventing/treating infection. This proposal will specifically evaluate stability and safety of antimicrobial nanosilver containing PLPs. The effectiveness of these particles will then be evaluated in a mouse model of bleeding and healing in the absence or presence of infection. Additionally, particle efficacy, safety, and immune system modulation will be evaluated in a rodent polytrauma model of combined traumatic brain injury (TBI) and hemorrhage.


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 = $584,108 )
2026	2026	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Blood Diseases and Resources Research	000	4	6/9/2026	NON-COMPETING CONTINUATION	$584,108
														Subtotal = $584,108

Issue Date FY: 2025 ( Subtotal = $596,029 )
2025	2025	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Blood Diseases and Resources Research	001	3	7/9/2025	NON-COMPETING CONTINUATION	$59,602
2025	2025	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Blood Diseases and Resources Research	000	3	4/1/2025	NON-COMPETING CONTINUATION	$536,427
														Subtotal = $596,029

Issue Date FY: 2024 ( Subtotal = $584,108 )
2024	2024	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Blood Diseases and Resources Research	000	2	5/15/2024	NON-COMPETING CONTINUATION	$584,108
														Subtotal = $584,108

Issue Date FY: 2023 ( Subtotal = $572,857 )
2023	2023	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Blood Diseases and Resources Research	000	1	3/13/2023	NEW	$572,857
														Subtotal = $572,857

Grand Total All Awards = $2,337,102

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Anti-microbial platelet-like-particles to treat internal bleeding and augment subsequent healing

Award Number: R01HL162809

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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