Christopher D. Roche , Haiyan Lin , Yizhou Huang , Charles E. de Bock , Dominik Beck , Meilang Xue , Carmine Gentile
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引用次数: 1
Abstract
Epicardial transplantation of 3D bioprinted patches represents a promising protective strategy against infarction-induced myocardial damage. We previously showed that 3D bioprinted tissues containing cardiac spheroids [in alginate/gelatin (AlgGel) hydrogels] promoted cell viability/function and endothelial cell tubular self-assembly. Here, we hypothesise that bioprinted cardiac spheroid patches improve cardiac function after myocardial infarction (MI). To determine treatment effects of hydrogel alone or with cells, MI mice were transplanted with: (i) AlgGel acellular patches, (ii) AlgGel with freely suspended cardiac cells, (iii) AlgGel with cardiac spheroids. We included control MI mice (no treatment) and mice undergoing sham surgery. We performed measurements to 28 days including echocardiography, flow cytometry and transcriptomic analyses. Our results measured median baseline (pre-surgery) left ventricular ejection fraction (LVEF%) for all mice at 66%. Post-surgery, LVEF% was 58% for Sham (non-infarcted) and 41% for MI (no treatment) mice. Patch transplantation increased LVEF%: 55% (acellular; p = 0.012), 59% (cells; p = 0.106), 64% (spheroids; p = 0.010). Flow cytometry demonstrated host cardiac tissue immune cell population changes with treatments. RNAseq transcriptomes demonstrated similar gene expression profiles for Sham and mice treated with cardiac spheroid patches. Extrusion 3D bioprinting permits hydrogel patch generation even preserving microtissue cardiac spheroids directly suspended in the bioink. Inflammatory and genetic mechanisms may play important roles in regulating host responses after patch transplantation in infarcted hearts. Future studies are needed to elucidate the possible immune cell and gene expression-related molecular mechanisms underlying these initial findings.
期刊介绍:
Bioprinting is a broad-spectrum, multidisciplinary journal that covers all aspects of 3D fabrication technology involving biological tissues, organs and cells for medical and biotechnology applications. Topics covered include nanomaterials, biomaterials, scaffolds, 3D printing technology, imaging and CAD/CAM software and hardware, post-printing bioreactor maturation, cell and biological factor patterning, biofabrication, tissue engineering and other applications of 3D bioprinting technology. Bioprinting publishes research reports describing novel results with high clinical significance in all areas of 3D bioprinting research. Bioprinting issues contain a wide variety of review and analysis articles covering topics relevant to 3D bioprinting ranging from basic biological, material and technical advances to pre-clinical and clinical applications of 3D bioprinting.