Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery

Abstract

Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. When implanted onto the myocardium, the patch releases NO locally through a stepwise biotransformation, and NO generation is remarkably enhanced in infarcted myocardium because of the ischemic microenvironment, which gives rise to mitochondrial-targeted cardioprotection as well as enhanced cardiac repair. The therapeutic efficacy is further confirmed in a clinically relevant porcine model of myocardial infarction. All these results support the translational potential of this functional patch for treating ischemic heart disease by therapeutic mechanisms different from conventional organic nitrate drugs.

A stem cell-derived ovarian regenerative patch restores ovarian function and rescues fertility in rats with primary ovarian insufficiency

“…Patching up the tissues represented a sustained delivery manner for therapeutics 47 . In this study, we fabricated a fully acellular ORP by embeding synMSC particles in a widely used SPS.…”

Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide

“…Briefly, PCL ( M n 80,000) was mixed with PCL-ONO 2 ( M n 2,000) at blending ratios of 9/1 (w/w), according to our previously published protocol ( Zhu et al, 2021 ). The mixture was dissolved in mixed chloroform/methanol (5:1, v/v) by sufficient stirring to obtain homogeneous solution with a final concentration of 10% (w/v).…”

“…NO is essential in maintaining cardiovascular homeostasis ( Yang et al, 2018 ) and dysfunctions in NO signaling is often an associated-complication of CVD pathologies ( Erdmann et al, 2013 ). NO-based interventions were shown to attenuate myocardial infarction ( Rassaf et al, 2014 ; Zhu et al, 2021 ), thrombus formation ( Heusch, 2015 ; Heusch and Gersh, 2017 ; Yang et al, 2020a ), and convey immunomodulatory and cardioprotective effects ( Bogdan, 2001 ; Chouchani et al, 2013 ). NO release or generation mechanisms have been incorporated into multiple cardiovascular implants, including stents ( Zhang et al, 2019 ; Yang et al, 2020b ) and vascular grafts ( Wang et al, 2015 ), with demonstratable benefits to the promotion of angiogenesis, re-endothelialization, and vascular tissue regeneration ( Yang et al, 2015 ; Li et al, 2018 ; Kabirian et al, 2019 ).…”

Therapeutic Acellular Scaffolds for Limiting Left Ventricular Remodelling-Current Status and Future Directions

“…In a very recent investigation, another research group produced a scaffold coupled with nitric oxide (NO), another cardioprotective agent [ 99 ]. Exogenous NO delivery exhibits its cardioprotective effect against MI injury, acting on CMs survival and improving their contractility.…”

“…Further, the therapeutic potential of these patches was translated into a large animal model of acute MI where they demonstrated suppressed adverse LV remodelling. Interestingly, besides enhanced cardiac function and decreased infarct size, this study reported a significant increase in CMs proliferation at the border zone of the infarct size accompanied by enhanced capillary and arteriolar density [ 99 ].…”