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 (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally 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 (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7-fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs.

Fluorogenic RNA-based biomaterials for imaging and tracking the cargo of extracellular vesicles.

Extracellular vesicles (EVs), or exosomes, play important roles in physiological and pathological cellular communication and have gained substantial traction as biological drug carriers. EVs contain both short and long non-coding RNAs that regulate gene expression and epigenetic processes. To fully capitalize on the potential of EVs as drug carriers, it is important to study and understand the intricacies of EV function and EV RNA-based communication.

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 instant adhesion to tissues (2.

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

Unlabelled: 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.

Discovery and characterization of a functional scFv for CCR2 inhibition via an extracellular loop.

The chemokine receptor CCR2 plays a key role in cellular migration and inflammatory processes. While tremendous progress has been made in elucidating CCR2 function and inhibition, the majority of approaches target its N-terminal domain and less is known about the function of the remaining extracellular loops and their potential as targets. Here, we used phage display to identify an antibody-derived scFv (single chain variable fragment) clone that specifically targets the second extracellular epitope of CCR2 (ECL2) for inhibition.

ZipperCells Exhibit Enhanced Accumulation and Retention at the Site of Myocardial Infarction.

There has been extensive interest in cellular therapies for the treatment of myocardial infarction, but bottlenecks concerning cellular accumulation and retention remain. Here, a novel system of in situ crosslinking mesenchymal stem cells (MSCs) for the formation of a living depot at the infarct site is reported. Bone marrow-derived mesenchymal stem cells that are surface decorated with heterodimerizing leucine zippers, termed ZipperCells, are engineered.