Vascular Discovery Scientic Sessions 2025  /  15. Poster Session 3 & Reception  /  Clickable Extracellular Vesicles for Localized Abdominal Aortic Aneurysm Repair
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American Heart Association

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Final ID: Th0006

Clickable Extracellular Vesicles for Localized Abdominal Aortic Aneurysm Repair

Abstract Body:

Introduction: Abdominal aortic aneurysm (AAA) features a degradative environment and loss of vascular elastin, which we believe could be treated with an engineered regenerative therapy. Our group and others have investigated using mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) for regeneration, but a key barrier to successful implementation is delivery. To address this problem, we have developed an EV delivery system that utilizes click chemistry to improve EV retention within a hydrogel.
Hypothesis: Click-bound EVs will have better retention within hydrogels compared to non-clicked EVs.
Methods: MSCs were cultured with or without Ac4ManNAz to metabolize an azido tag onto the EVs. After isolation the EVs were labeled with NHs-Cy5 and excess dye was removed by dialysis. DBCO-conjugated fibrinogen and collagen were mixed to form a “hybridgel” with different release characteristics depending on the concentration of each protein. The final concentration of the gel was 7.5 mg/mL with the DBCO collagen gel being a 2:1 mixture with WT collagen and the hybridgel being a 50:50 mixture of collagen and fibrinogen. EVs were characterized by Western blot and nanoparticle tracking analysis. EVs were co-cultured with SMCs in fibrin gels for 6h to assess EV uptake.
Results and Conclusions: DBCO-conjugated collagen and fibrinogen had better EV retention than their wild type counterparts. Collagen had better retention compared to fibrinogen, and the hybridgel had a retention profile between the two. Co-culture of EVs with fibrin gels demonstrated uptake into SMCs compared to dye controls.
Conclusions/Interpretations: A hybridgel of collagen and fibrinogen can be used to tailor retention. EVs can be taken up by SMCs in 3D fibrin constructs.
  • Marini, Ande  ( University of Pittsburgh , Pittsburgh , Pennsylvania , United States )
  • Otto, Ellen  ( Carnegie Mellon University , Pittsburgh , Pennsylvania , United States )
  • Li, Bo  ( Vanderbilt University Medical Center , Nashville , Tennessee , United States )
  • Weinbaum, Justin  ( University of Pittsburgh , Pittsburgh , Pennsylvania , United States )
  • Ren, Xi  ( Carnegie Mellon University , Pittsburgh , Pennsylvania , United States )
  • Campbell, Phil  ( Carnegie Mellon University , Pittsburgh , Pennsylvania , United States )
  • Curci, John  ( Vanderbilt University Medical Center , Nashville , Tennessee , United States )
  • Vorp, David  ( University of Pittsburgh , Pittsburgh , Pennsylvania , United States )
    • Author Disclosures:
    Ande Marini: DO NOT have relevant financial relationships | Ellen Otto: DO NOT have relevant financial relationships | Bo Li: DO NOT have relevant financial relationships | Justin Weinbaum: No Answer | Xi Ren: No Answer | Phil Campbell: No Answer | John Curci: DO NOT have relevant financial relationships | David Vorp: DO have relevant financial relationships ; Ownership Interest:Aneurisk, Inc.:Active (exists now) ; Individual Stocks/Stock Options:Aneurisk, Inc.:Active (exists now) ; Executive Role:Aneurisk, Inc.:Active (exists now)
Meeting Info:

Vascular Discovery Scientic Sessions 2025

2025

Baltimore, MD

Session Info:

15. Poster Session 3 & Reception

Thursday, 04/24/2025 , 05:00PM - 07:00PM

Poster

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