Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.01.31.478512

Surface engineering enhances the therapeutic potential of extracellular vesicles following acute myocardial infarction

Mentkowski, K. I.·Tarvirdizadeh, T.·Manzanero, C. A.·Eagler, L. A.·Lang, J. K.
View original source ↗Export metadata ↓

Abstract

Structured AbstractO_ST_ABSObjectivesC_ST_ABSThe objective of the study was to assess the therapeutic efficacy of targeting remote zone cardiomyocytes with cardiosphere-derived cell (CDC) extracellular vesicles (EVs) in acute myocardial infarction. BackgroundCardiomyocyte (CM) cell death plays a significant role in left ventricular (LV) remodeling and cardiac dysfunction following myocardial infarction (MI). While EVs secreted by CDCs have shown efficacy in promoting cardiac repair in preclinical models of MI, their translational potential is limited by their biodistribution. We hypothesized that targeting therapeutic EVs to CMs would result in further reduction of cardiomyocyte (CM) cell death in vivo and improvement in cardiac function post-MI. MethodsCDC-derived EVs were engineered to express a CM-specific binding peptide (CMP) on their surface and characterized for size, morphology, and protein expression. Mice with acute MI underwent delivery of human CDC EVs, CMP-EVs and placebo in a double-blind study. LVEF was assessed by echo at 1- and 28-days post-MI and tissue samples processed for assessment of EV biodistribution and histological endpoints. ResultsCMP-EVs demonstrated superior cardiac targeting and retention when compared with control EVs 24 hours post MI. While intramyocardial administered CDC-EVs improved LVEF compared with placebo at 4 weeks, mice treated with CMP-EVs demonstrated a significant improvement in LVEF compared with non-targeted EVs. Likely accounting for their augmented therapeutic efficacy, CMP-EVs demonstrated enhanced reduction of remote zone cardiomyocyte apoptosis. ConclusionsTargeting CMP-EVs to CMs post-MI improved cardiac function compared with unmodified EVs demonstrating a strategy to further optimize therapeutic EV delivery to increase efficacy and decease off-target effects. Condensed AbstractExtracellular vesicles (EVs) offer several potential advantages over small molecule therapeutics for cardiovascular disease (CVD). However, their potential is limited by their biodistribution and lack of specificity. We engineered cardiosphere-derived cells (CDCs) to express Lamp2b fused to a cardiomyocyte specific peptide (CMP), generating EVs with increased cardiomyocyte uptake and cardiac retention. CMP-EVs enhanced cardiac function following acute MI and further reduced remote zone apoptosis when compared with unmodified CDC-EVs. This work highlights a role for targeting therapeutic EVs to cardiomyocytes following injury and serves as a proof-of-concept study for the utility of EV surface engineering in the treatment of CVD.

Explore related subjects

bioengineeringPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mentkowski, K. I., Tarvirdizadeh, T., Manzanero, C. A., Eagler, L. A., Lang, J. K.. 2022-02-02. Surface engineering enhances the therapeutic potential of extracellular vesicles following acute myocardial infarction. https://doi.org/10.1101/2022.01.31.478512

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Single-Component Photo-Crosslinked Lipoic Acid Functionalized Mucin Hydrogels: Dynamic Mucus Mimetics for Antiviral Protection

Native mucus protects epithelial surfaces through viscoelastic networks of disulfide-linked mucins. However, commercially available mucins often fail to reconstitute comparable mechanical and barrier properties, while synthetic and hybrid mucus mimetics require polymeric crosslinkers that may alter mucus-like composition. Inspired by the native architecture, we directly functionalized porcine gastric and bovine submaxillary mucins with -lipoic acid to develop a single-component, photo-crosslinkable hydrogels. Upon UV irradiation (365 nm), the modified mucins rapidly form disulfide-crosslinked networks without added photo-initiator/ polymeric crosslinkers, two orders of magnitude faster as compared with PEG-SH approaches. The resulting mucin-lipoic acid (MUC-LA) hydrogels exhibit mucus-relevant properties, including tunable viscoelasticity, redox responsiveness, self-healing, and size-dependent restrictions on nanoparticle transport. In transwell-based infection models, MUC-LA hydrogels (2-3%) mimicking the healthy airway mucus (G' {approx} 10-20 Pa) suppress epithelial infection by SARS-CoV-2 and influenza A virus. Crosslinked MUC-LA provides greater protection against SARS-CoV-2 than the non-crosslinked, whereas both formulations suppress influenza A infection, suggesting distinct contributions from network formation and mucin-associated interactions. These findings establish a dynamic, mucus-mimetic platform integrating rapid photo-gelation, controllable mechanics, selective transport, and antiviral barrier functionality. MUC-LA hydrogels offer opportunities to investigate mucosal transport and host-pathogen interactions, with potential applications in drug delivery, and as biomaterials.

bioengineering↗
bioRxiv2026

A Fibrous Optofluidic Probe for Endovascular Sensing of Blood Oxygenation and Flow Velocity

Local hemodynamic information including blood oxygenation and flow velocity could guide vascular interventions, yet obtaining these parameters in deep, narrow vessels remains challenging. Here, we report a flexible, submillimeter-scale fibrous optofluidic probe for endovascular sensing of blood oxygenation and flow velocity. The probe integrates a polymer optical fiber for light transmission with a microfluidic tube for dye injection, enabling spectroscopic oximetry and fluorescence dilution-based velocimetry through a single device. Via vascular intervention, we demonstrate local hemodynamic sensing in rabbit arteries and angiography-guided deployment in canine carotid arteries. The probe captures local changes in blood oxygenation and flow velocity during vascular occlusion and reperfusion, revealing hemodynamic disturbances that are not reflected in peripheral monitors. These results illustrate the complementary information provided by local oximetry and velocimetry and establish a compact optofluidic platform for quantitative hemodynamic monitoring during vascular interventions.

bioengineering↗
bioRxiv2026

Broad-spectrum in situ genetic reprogramming of native microbiomes

Complex microbial communities are found throughout terrestrial, aquatic, and animal-associated ecosystems. Genetic modification of discrete microbial taxa within native communities represents a powerful tool to study and augment microbiome functions. Herein, we develop Synthetic Phage Assisted Reprogrammable and Targetable Addition (SPARTA) as a one-step strategy for packaging, delivering, and integrating large synthetic DNA into a broad range of native microbiomes. SPARTA leverages a broad-spectrum synthetic phage particle for in situ genome engineering within complex soil, freshwater, and mammalian fecal microbiomes, reprogramming 59 native species across 16 families. By modulating SPARTA components, we further demonstrated tunability of SPARTA towards targeted microbiome population. Additionally, we built a novel companion tool to quantitatively identify engineered taxa, named 16S crRNA-guided inference of bacterial engineering sequencing or ScRibe-seq. The SPARTA-ScRibe-seq pipeline delivered and validated functional synthetic gene clusters in diverse native microbiomes while preserving the original microbial community structure. Together, this novel genome engineering framework constitutes an end-to-end programmable platform for rational and customizable reprogramming of native microbiomes.

bioengineering↗