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      Oxygen-Generating Scaffolds for Cardiac Tissue Engineering Applications

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          Abstract

          Homogeneous vascularization of implanted tissue constructs can extend to 5 weeks, during which cell death can occur due to inadequate availability of oxygen. Researchers are engineering biomaterials that generate and release oxygen in a regulated manner, in an effort to overcome this hurdle. A main limitation of the existing oxygen-generating biomaterials is the uncontrolled release of oxygen, which is ultimately detrimental to the cells. This study demonstrates the incorporation of calcium peroxide (CaO2) within a hydrophobic polymer, polycaprolactone (PCL), to yield composite scaffolds with controlled oxygen release kinetics sustained over 5 weeks. Oxygen-generating microparticles coencapsulated with cardiomyocytes in a gelatin-based hydrogel matrix can serve as model systems for cardiac tissue engineering. Specifically, the results reveal that the oxygen-generating microspheres significantly improve the scaffold mechanical strength ranging from 5 kPa to 35 kPa, have an average scaffold pore size of 50-100 μm, swelling ratios of 33.3-29.8%, and degradation with 10-49% remaining mass at the end of a 48 h accelerated enzymatic degradation. The oxygen-generating scaffolds demonstrate improvement in cell viability, proliferation, and metabolic activity compared to the negative control group when cultured under hypoxia. Additionally, the optimized oxygen-generating constructs display no cytotoxicity or apoptosis. These oxygen-generating scaffolds can possibly assist the in vivo translation of cardiac tissue constructs.

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          Most cited references59

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          Oxygen, oxidative stress, hypoxia, and heart failure

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            Analysis of Cell Viability by the Lactate Dehydrogenase Assay

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              Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity

              Environmental factors are the largest contributors to cardiovascular disease. Here, we show that cardiac organoids incorporating an oxygen-diffusion gradient and stimulated via the neurotransmitter norepinephrine can structurally model the human heart after myocardial infarction (mimicking the gradient of infarct, border, and remote zones), and recapitulate hallmarks of myocardial infarction (such as pathological metabolic shifts, fibrosis and calcium handling) at the transcriptomic, structural and functional levels. We also demonstrate that the organoids can model hypoxia-enhanced doxorubicin cardiotoxicity. Human organoids that model diseases with non-genetic pathological factors could aid drug screening and development.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                ACS Biomaterials Science & Engineering
                ACS Biomater. Sci. Eng.
                American Chemical Society (ACS)
                2373-9878
                2373-9878
                January 09 2023
                December 05 2022
                January 09 2023
                : 9
                : 1
                : 409-426
                Affiliations
                [1 ]Biomedical Engineering and Biotechnology Program, University of Massachusetts Lowell, One University Avenue, Lowell, Massachusetts 01854, United States
                [2 ]Department of Chemical Engineering, University of Massachusetts Lowell, One University Avenue, Lowell, Massachusetts 01854, United States
                [3 ]Department of Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01605, United States
                Article
                10.1021/acsbiomaterials.2c00853
                903d7dd6-1856-404c-a6e8-e74a6dd41742
                © 2023

                https://doi.org/10.15223/policy-029

                https://doi.org/10.15223/policy-037

                https://doi.org/10.15223/policy-045

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