Biology subjects

Jasiewicz, N.

Publications and source records attributed to Jasiewicz, N..

3 recordsLinked to original sources

bioRxiv2024

In Situ-Crosslinked Zippersomes Enhance Cardiac Repair by Increasing Accumulation and Retention

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction, but their therapeutic efficacy is limited by inefficient accumulation at the target site. A non-invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here we show that EVs decorated with the next-generation of high-affinity heterodimerizing leucine zippers, termed high-affinity (HiA) Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited [~]7-fold enhanced accumulation within the infarcted myocardium in mice after three days and continued to be retained up to day 21, surpassing the performance of unmodified EVs. After myocardial infarction in mice, high-affinity Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and PBS, respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. High-affinity Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for non-invasive vesicle delivery to the infarcted heart. Translational Impact StatementTherapeutic delivery to the heart remains inefficient and poses a bottleneck in modern drug delivery. Surgical application and intramyocardial injection of therapeutics carry high risks for most heart attack patients. To address these limitations, we have developed a non-invasive strategy for efficient cardiac accumulation of therapeutics using in situ crosslinking. Our approach achieves high cardiac deposition of therapeutics without invasive intramyocardial injections. Patients admitted with myocardial infarction typically receive intravenous access, which would allow painless administration of Zippersomes alongside standard of care.

bioengineering↗

bioRxiv2022

Instantly adhesive and ultra-elastic patches for dynamic organ and wound repair

Bioadhesive materials and patches are promising alternatives to surgical sutures and staples. However, many existing bioadhesives do not meet the functional requirements of current surgical procedures and interventions. Here we present a translational patch material that exhibits: (1) instant adhesion to wet tissues (2.5-fold stronger than Tisseel, an FDA-approved fibrin glue), (2) ultra-stretchability (stretching to >300% its original length without losing elasticity), (3) compatibility with rapid photo-projection (<2 min fabrication time/patch), and (4) ability to deliver therapeutics. Using our established procedures for the in silico design and optimization of anisotropic-auxetic patches, we create next generation patches for instant attachment to wet and dry tissues while conforming to a broad range of organ mechanics ex vivo and in vivo. Patches coated with exosomes demonstrate robust wound healing capability in vivo without inducing a foreign body response and without the need for patch removal that can cause pain and bleeding. We further demonstrate a new single material-based, void-filling auxetic patch designed for the treatment of lung puncture wounds. TeaserWe demonstrate a sticky and highly elastic patch with conforming designs for dynamic organ repair.

bioengineering↗

bioRxiv2020

MiR-101a loaded Extracellular Nanovesicles as Bioactive Carriers for Cardiac Repair

Myocardial infarction (MI) remains a major cause of mortality worldwide. Despite significant advances in MI treatment, many who survive the acute event are at high risk of chronic cardiac morbidity. Here we developed a cell-free therapeutic that capitalizes on the antifibrotic effects of micro(mi)RNA-101a and exploits the multi-faceted regenerative activity of mesenchymal stem cell (MSC) extracellular nanovesicles (eNVs). While the majority of MSC eNVs require local delivery via intramyocardial injection to exert therapeutic efficacy, we have developed MSC eNVs that can be administered in a minimally invasive manner, all while remaining therapeutically active. When loaded with miR-101a, MSC eNVs substantially decreased infarct size (12 {+/-} 2.4% vs. 21.4 {+/-} 5.7%) and increased ejection fraction (53.6 {+/-} 7.6% vs. 40.3 {+/-} 6.0%) and fractional shortening (23.6 {+/-} 4.3% vs. 16.6 {+/-} 3.0%) compared to control. These findings are significant as they represent an advance in the development of minimally invasive cardio-therapies.

bioengineering↗