Myocardial Matrix Hydrogels Mitigate Negative Remodeling and Improve Function in Right Heart Failure Model.

This study evaluates the effectiveness of myocardial matrix (MM) hydrogels in mitigating negative right ventricular (RV) remodeling in a rat model of RV heart failure. The goal was to assess whether a hydrogel derived from either the right or left ventricle could promote cardiac repair. Injured rat right ventricles were injected with either RV-or left ventricular-derived MM hydrogels.

Immunomodulatory contribution of mast cells to the regenerative biomaterial microenvironment.

Bioactive immunomodulatory biomaterials have shown promise for influencing the immune response to promote tissue repair and regeneration. Macrophages and T cells have been associated with this response; however, other immune cell types have been traditionally overlooked. In this study, we investigated the role of mast cells in the regulation of the immune response to decellularized biomaterial scaffolds using a subcutaneous implant model.

Inflammation-Responsive Micellar Nanoparticles from Degradable Polyphosphoramidates for Targeted Delivery to Myocardial Infarction.

Nanoparticles that undergo a localized morphology change to target areas of inflammation have been previously developed but are limited by their lack of biodegradability. In this paper, we describe a low-ring-strain cyclic olefin monomer, 1,3-dimethyl-2-phenoxy-1,3,4,7-tetrahydro-1,3,2-diazaphosphepine 2-oxide (MePTDO), that rapidly polymerizes via ring-opening metathesis polymerization at room temperature to generate well-defined degradable polyphosphoramidates with high monomer conversion (>84%). Efficient MePTDO copolymerizations with norbornene-based monomers are demonstrated, including a norbornenyl monomer functionalized with a peptide substrate for inflammation-associated matrix metalloproteinases (MMPs).

Intravascularly Deliverable Biomaterial Platforms for Tissue Repair and Regeneration Post-Myocardial Infarction.

Each year, nearly 19 million people die of cardiovascular disease with coronary heart disease and myocardial infarction (MI) as the leading cause of the progression of heart failure. Due to the high risk associated with surgical procedures, a variety of minimally invasive therapeutics aimed at tissue repair and regeneration are being developed. While biomaterials delivered via intramyocardial injection have shown promise, there are challenges associated with delivery in acute MI.

Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues.

Decellularized extracellular matrix in the form of patches and locally injected hydrogels has long been used as therapies in animal models of disease. Here we report the safety and feasibility of an intravascularly infused extracellular matrix as a biomaterial for the repair of tissue in animal models of acute myocardial infarction, traumatic brain injury and pulmonary arterial hypertension. The biomaterial consists of decellularized, enzymatically digested and fractionated ventricular myocardium, localizes to injured tissues by binding to leaky microvasculature, and is largely degraded in about 3 d.

MEK inhibition enhances presentation of targetable MHC-I tumor antigens in mutant melanomas.

Combining multiple therapeutic strategies in NRAS/BRAF mutant melanoma-namely MEK/BRAF kinase inhibitors, immune checkpoint inhibitors (ICIs), and targeted immunotherapies-may offer an improved survival benefit by overcoming limitations associated with any individual therapy. Still, optimal combination, order, and timing of administration remains under investigation. Here, we measure how MEK inhibition (MEKi) alters anti-tumor immunity by utilizing quantitative immunopeptidomics to profile changes in the peptide major histocompatibility molecules (pMHC) repertoire.

Myocardial matrix hydrogel acts as a reactive oxygen species scavenger and supports a proliferative microenvironment for cardiomyocytes.

As the native regenerative potential of adult cardiac tissue is limited post-injury, stimulating endogenous repair mechanisms in the mammalian myocardium is a potential goal of regenerative medicine therapeutics. Injection of myocardial matrix hydrogels into the heart post-myocardial infarction (MI) has demonstrated increased cardiac muscle and promotion of pathways associated with cardiac development, suggesting potential promotion of cardiomyocyte turnover. In this study, the myocardial matrix hydrogel was shown to have native capability as an effective reactive oxygen species scavenger and protect against oxidative stress induced cell cycle inhibition in vitro.

Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition.

Peptides bound to class I major histocompatibility complexes (MHC) play a critical role in immune cell recognition and can trigger an antitumor immune response in cancer. Surface MHC levels can be modulated by anticancer agents, altering immunity. However, understanding the peptide repertoire's response to treatment remains challenging and is limited by quantitative mass spectrometry-based strategies lacking normalization controls.

Apoptotic Bodies Elicit Gas6-Mediated Migration of AXL-Expressing Tumor Cells.

Metastases are a major cause of cancer mortality. AXL, a receptor tyrosine kinase aberrantly expressed in many tumors, is a potent oncogenic driver of metastatic cell motility and has been identified as broadly relevant in cancer drug resistance. Despite its frequent association with changes in cancer phenotypes, the precise mechanism leading to AXL activation is incompletely understood.