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Engineering Surface Coatings for Localized Delivery of Therapeutic Extracellular Vesicles

Award Number: R16GM151369
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/07/2023
PERIOD OF PERFORMANCE END DATE: 05/28/2024

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Engineering Surface Coatings for Localized Delivery of Therapeutic Extracellular Vesicles - PROJECT SUMMARY The PI’s long-term research goal is to engineer the cell-material interface for applications in tissue engineering, regenerative medicine, and medical implants, with a particular focus on bone regeneration. Extracellular vesicle (EV) - based therapies have been of increasing interest in the past decade to treat a variety of pathologies. Although EV delivery from various carrier systems has been shown to induce tissue regeneration in preclinical models, there remains a critical gap in efficient and controlled delivery of therapeutic EVs. This proposal aims to engineer a surface coating system that promotes localized EV delivery for tissue engineering and regenerative medicine applications. The central hypothesis underlying this research is that surface-mediated EV delivery modulates cellular uptake and signaling in comparison to bolus or systemic EV delivery. The specific research objectives of this proposal are to: (1) Investigate the roles of electrostatic and receptor- ligand interactions in the adsorption and release of EVs to/from surface coatings; (2) Investigate the effects of surface-based EV delivery in comparison to bolus EV delivery; and, (3) Demonstrate that EV delivery from surface-coated tissue engineering scaffolds improves tissue regeneration in vivo in a rat spinal fusion model. EVs will be derived from mesenchymal stem/stromal cells (MSCs) and characterized for size, surface charge, and protein markers. Interactions between MSC-EVs and surface coatings composed of ECM proteins, polysaccharides and charged polymers will be analyzed under various conditions (pH, R-L inhibitors, salt screening) via fluorescence labeling studies and quartz crystal microbalance with dissipation analyses. EV uptake efficiency and endocytic pathways will be analyzed in several cell types (MSCs, HUVECs, HEK293s) in comparison to bolus EV delivery via fluorescence microscopy and flow cytometry (+/- endocytic pathway inhibitors). Cellular adhesion, proliferation, and angiogenic differentiation and immunomodulation will also be analyzed in vitro. In vivo bone forming capacity and fusion efficacy of EVs delivered from surface-coated scaffolds will be evaluated in the rat posterolateral lumbar fusion model via manual palpation, radiographic scoring, volumetric microcomputed tomography (µCT) and immunohistochemistry, in comparison to uncoated scaffolds and bolus delivery. Results from this work will significantly advance understanding of how material properties and surface-based EV delivery impact cellular EV uptake, adhesion, proliferation and differentiation. Additionally, this proposal will enable development of effective therapeutic EV surface-coatings that can tailored for a wide variety of scaffolds and/or implants for many different therapies, including cartilage regeneration, diabetic wound healing, cardiac infarction, and tendon and muscle repair.


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: 2025 ( Subtotal = -$128,141 )
2025	2023	FLORIDA A & M UNIVERSITY	1700 LEE HALL DR #201	TALLAHASSEE	FL	32307	LEON	USA	Biomedical Research and Research Training	000	1	11/18/2024	NEW	-$128,141
														Subtotal = -$128,141

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	FLORIDA A & M UNIVERSITY	1700 LEE HALL DR #201	TALLAHASSEE	FL	32307	LEON	USA	Biomedical Research and Research Training	000	1	8/20/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $170,622 )
2023	2023	FLORIDA A & M UNIVERSITY	1500 WAHNISH WAY	TALLAHASSEE	FL	32307	LEON	USA	Biomedical Research and Research Training	000	1	7/7/2023	NEW	$170,622
														Subtotal = $170,622

Grand Total All Awards = $42,481

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Engineering Surface Coatings for Localized Delivery of Therapeutic Extracellular Vesicles

Award Number: R16GM151369

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/07/2023

PERIOD OF PERFORMANCE END DATE: 05/28/2024

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