ArticleJournal of controlled release : official journal of the Controlled Release Society2018
Injectable and protease-degradable hydrogel for siRNA sequestration and triggered delivery to the heart.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 114 citations in OpenAlex.
- Research advances in intelligent microenvironment-responsive hydrogels for myocardial infarction therapy.APL bioengineering · 2026Review
- Intelligent design and application of molecular recognition hydrogels in tissue engineering.Materials today. Bio · 2026Review
- Review
- Bridging miRNA Research with Clinical Applications in Cardiovascular Diseases: Advances in Delivery Systems and Therapeutic Strategies.Mini reviews in medicinal chemistry · 2026Review
- Smart Polymer-Derived Injectable Hydrogels: Current Status and Future Perspectives.ACS polymers Au · 2025Review
- Biomaterial-Based Nucleic Acid Delivery Systems for In Situ Tissue Engineering and Regenerative Medicine.International journal of molecular sciences · 2025Review
- Hydrogels in Cardiac Surgery: Versatile Platforms for Tissue Repair, Adhesion Prevention, and Localized Therapeutics.Gels (Basel, Switzerland) · 2025Review
- Matrix Metalloproteinases: Pathophysiologic Implications and Potential Therapeutic Targets in Cardiovascular Disease.Biomolecules · 2025Review
- Engineering and Monitoring the Sustained Release of Extracellular Vesicles from Hydrogels forAdvanced nanobiomed research · 2024Article
- Local and Sustained Baricitinib Delivery to the Skin through Injectable Hydrogels Containing Reversible Thioimidate Adducts.Advanced healthcare materials · 2024Article
- Developing hydrogels for gene therapy and tissue engineering.Journal of nanobiotechnology · 2024Review
- Beyond Traditional Medicine: EVs-Loaded Hydrogels as a Game Changer in Disease Therapeutics.Gels (Basel, Switzerland) · 2024Review
- Application of Hydrogels in Cardiac Regeneration.Cardiology and therapy · 2023Review
- Small Molecule-Templated DNA Hydrogel with Record Stiffness Integrates and Releases DNA Nanostructures and Gene Silencing Nucleic Acids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Matrix Metalloproteinase-Targeted SPECT/CT Imaging for Evaluation of Therapeutic Hydrogels for the Early Modulation of Post-Infarct Myocardial Remodeling.Journal of cardiovascular translational research · 2023Article
- Biomembrane-Based Nanostructure- and Microstructure-Loaded Hydrogels for Promoting Chronic Wound Healing.International journal of nanomedicine · 2023Review
- Fabrication and characterization of novel macroporous hydrogels based on the polymerizable surfactant AAc-Span80 and their enhanced drug-delivery capacity.RSC advances · 2022Article
- Intelligent Hydrogels in Myocardial Regeneration and Engineering.Gels (Basel, Switzerland) · 2022Review
- Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter-Particle Crosslinking.Small (Weinheim an der Bergstrasse, Germany) · 2022Article
- Biosensor-Integrated Drug Delivery Systems as New Materials for Biomedical Applications.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Injectable hydrogels have significant therapeutic potential for treatment of myocardial infarction (MI) through tissue bulking and local drug delivery, including the delivery of small interfering RNAs (siRNAs). As siRNA targets are identified as potential treatments for MI, hydrogels may bolster efficacy through local and sustained release. Here, we designed an injectable hydrogel to respond to local upregulation in proteolytic activity after MI to erode and release siRNA against MMP2 (siMMP2), a target implicated in deleterious remodeling. Specifically, hyaluronic acid (HA) was modified with hydrazides or aldehydes and mixed to form shear-thinning and self-healing hydrogels through dynamic hydrazone bonds and with peptide crosslinkers that degrade in response to protease activity. HA was further modified with β-cyclodextrin to sequester cholesterol-modified siRNA, limiting passive diffusion. Hydrogels eroded in response to proteases and released active siRNA that knocked down MMP2 in primary cardiac fibroblasts. In a rat model of MI, hydrogels delivering siMMP2 attenuated hydrogel erosion by ~46% at 4 weeks when compared to hydrogels delivering control siRNA, ultimately improving myocardial thickness in the infarct. Delivery of the siMMP2 hydrogel led to significant functional improvements, including increased ejection fraction (27%, 66%), stroke volume (32%, 120%), and cardiac output (20%, 128%) when compared to controls (% increase versus hydrogels with control siRNA, % increase versus saline injection alone). This report demonstrates the utility of biomaterial-based RNA delivery systems for cardiac applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.