Extracellular matrices (ECMs) Biomaterials provide new strategies for areas such as tissue engineering scaffolds and regenerative medicine. ECM can be enzymatically processed into inducible hydrogel , which can be injected into tissues for minimally invasive drug delivery. These degradable hydrogels have a series of regenerative functions such as pro-survival, immune regulation, and promotion of blood vessel formation.
Current ECM biomaterials are limited to surgically implanted patches or local injections. Due to their physical properties, they cannot enter the gaps of the leaky endothelium at the site of injury or disease. This makes it difficult for ECM to be delivered quickly and uniformly to the injured site, and is not suitable for tissues that are difficult to implant with conventional techniques, such as the heart, brain, and lungs. Based on this challenge, a team led by Professor Karen L. Christman at the University of California, San Diego, developed an ECM biomaterial that can be used for intravascular infusion and demonstrated its safety and feasibility in repairing tissue in animal models of acute myocardial infarction, traumatic brain injury, and pulmonary hypertension. The related results were published in the latest issue of Nature Biomedical Engineering as "Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues" .
[Article Highlights]
Vascularly Infusible Extracellular Matrix Biomaterials (iECM)
Vascularly Infusable Extracellular Matrix Biomaterials (iECM) are composed of decellularized, enzymatically digested, and isolated ventricular myocardium, localize to damaged tissue by binding to leaky microvasculature, and undergo extensive degradation within approximately 3 days. This material uses decellularized myocardial ECM hydrogel as the raw material, and removes large sub-micron particles such as high molecular weight peptides/proteins, allowing it to pass through the leaky vascular space in acute injury or inflammation sites. After testing with human blood, iECM is blood compatible.
Figure 1. Preparation and architecture of iECM
iECM combined with damaged endothelial cells
Unlike materials such as alginate, iECM is wrapped or filled in the gaps of the leaking endothelial cells layer, rather than passing through the gaps and entering the injured tissue. Histology showed that the material was observed between endothelial cells, and using an in vitro model, the material was found to bind to injured and inflamed human endothelial cells, particularly in areas where the underlying ECM had been exposed. The study further found that iECM not only physically blocks gaps in leaking blood vessels immediately after infusion, but also helps accelerate the healing and closure of blood vessels as it degrades. iECM has also been found to increase platelet adhesion in vitro at lower shear rates, which may also aid blood vessel healing in vivo.
Figure 2. iECM binds to damaged endothelial cells and promotes platelet adhesion in vitro
Application of iECM in animal models
Three preclinical models were selected to observe different situations of leaky vasculature, namely acute myocardial infarction (MI), traumatic brain injury and pulmonary hypertension, which represent acute and chronic injuries, while also covering ischemic, traumatic and pressure overload injuries. In all models, iECM targeted distribution to injured tissue, suggesting that leaky vasculature is required for material to lodge. In a rat acute MI model, iECM significantly reduced left ventricular volume, end-systolic volume, and end-diastolic volume. In a large animal porcine model of acute MI, left ventricular wall thickness was significantly reduced, indicating possible reduction in edema, and overall wall motion index scores were improved.
Figure 3. iECM significantly improves cardiac function after myocardial infarction in a rat acute MI model
[Summary ]
This study developed a new ECM material that can be used for vascular infusion, demonstrating the feasibility of intravascular targeted delivery of iECM to injured and diseased tissues with vascular leakage. The material has broad applicability in models of acute myocardial infarction, traumatic brain injury and pulmonary hypertension and is hemocompatible, with no evidence of embolism found, indicating that the material can be safely delivered into blood vessels.When the biomaterial was injected into the coronary artery under induction of acute myocardial infarction in rats and pigs, a substantial reduction in left ventricular volume, improvement in wall motion scores, and differential expression of genes related to tissue repair and inflammation were observed. Providing healing-friendly extracellular matrix via intravascular infusion after injury may provide a solution for healing injured tissues with leaky vasculature.
[About the author ]
Karen L. Christman, professor in the Department of Bioengineering at the University of California, San Diego. He received his bachelor's degree in biomedical engineering from Northwestern University in 2000 and his doctorate from the joint bioengineering graduate group at the University of California, San Francisco and Berkeley in 2003. He then became a postdoctoral researcher at the National Institutes of Health and joined the University of California, San Diego in 2007. Her laboratory focuses on the development of novel biomaterials for tissue engineering and regenerative medicine, with the primary goal of developing novel minimally invasive treatments for cardiovascular disease. She is also the co-founder of Ventrix.
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Original link:
https://www.nature.com/articles/s41551-022-00964-5
Source: BioMed Technology
