Bioengineered Self-Adhering Electrospun Nanoscaffolds to Deliver Mitochondrial Antioxidant, JP4-039
Abstract Body (Do not enter title and authors here): Introduction: Treatment of pathologic remodeling and subsequent decline in cardiac function post-myocardial infarction (MI) remains limited. Our lab has previously demonstrated that the targeted mitochondrial antioxidant, JP4-039 (JP4), can abrogate post-MI remodeling and decline in cardiac function, and that JP4 released from electrospun nanoscaffolds improved proliferation and migration of coronary vascular endothelial cells in vitro. The aims of this study were to develop a suture-free, bioadhesive electrospun nanoscaffold that will adhere post-MI cardiac tissue and reliably release JP4 in a localized manner.
Hypothesis: Plasma treatment of JP4-loaded biocompatible electrospun nanoscaffold will adhere to cardiac tissue and deliver active moiety of JP4.
Methods: A 2% poly(l-lactide-co-glycolide) (PGLA) was electrospun with and without 1% JP4. Nanoscaffolds then underwent plasma treatment for one minute followed by a force adhesion assay. SEM imaging and electron paramagnetic resonance (EPR) assays before and after plasma treatment of both control and JP4-loaded patches were performed to examine patch consistency and ensure the release of the unaltered, active structure of JP4.
Results: JP4 loading and plasma treatment did not affect fiber dimeter of the scaffolds (p > 0.5 for all; Fig. 1B). JP4-loaded patches demonstrated similar release pattern of the antioxidant’s nitroxide moiety by displaying a characteristic triple peak both before and after plasma treatment as determined by EPR (Fig. 1C). Plasma-treated patches demonstrated significant increase in force adhesion compared to non-treated patches in both the control and JP4-loaded scaffolds (p < 0.0001) (Fig. 1A.). No significant difference in force adhesion was observed between the plasma treated control and JP4 loaded patch (p > 0.05) as determined by ANOVA (Fig. 1A). There was no significant difference in force adhesion between one minute and two minutes of plasma treatment (p > 0.05; Fig. 1A lower panel).
Conclusion: The findings demonstrate that plasma-treated biocompatible JP4-loaded patches may reliably adhere to cardiac tissue and release the bioactive component of the mitochondrial antioxidant, JP4.
Broadwin, Mark
( Rhode Island Hospital
, Sudbury
, Massachusetts
, United States
)
Abid, Ruhul
( BROWN UNIV WARREN ALPERT MED
, Providence
, Rhode Island
, United States
)
Oh, Amy
( Brown University
, Providence
, Rhode Island
, United States
)
Imarhia, Frances
( Brown University
, Providence
, Rhode Island
, United States
)
Ferbert, Mason
( Brown University
, Providence
, Rhode Island
, United States
)
Lyakhovych, Zakhar
( Brown University
, Providence
, Rhode Island
, United States
)
Teixeira, Rayane
( Rhode Island Hospital
, Providence
, Rhode Island
, United States
)
Wipf, Peter
( University of Pittsburgh
, Pittsburgh
, Pennsylvania
, United States
)
Bhowmick, Sankha
( UMASS Dartmouth
, N Dartmouth
, Massachusetts
, United States
)
Sellke, Frank
( Brown Medical School
, Providence
, Rhode Island
, United States
)
Author Disclosures:
Mark Broadwin:DO NOT have relevant financial relationships
| Ruhul Abid:DO have relevant financial relationships
;
Consultant:XM Therapeutics:Active (exists now)
; Executive Role:Health and Education for All (non-profit, 501c3):Active (exists now)
; Consultant:Alamgir Research Inc:Past (completed)
| Amy Oh:No Answer
| Frances Imarhia:DO NOT have relevant financial relationships
| Mason Ferbert:No Answer
| Zakhar Lyakhovych:DO NOT have relevant financial relationships
| Rayane Teixeira:No Answer
| Peter Wipf:No Answer
| Sankha Bhowmick:No Answer
| Frank Sellke:DO have relevant financial relationships
;
Ownership Interest:Xm therapeutics:Active (exists now)