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Self-oxygenation of engineered living tissues orchestrates osteogenic commitment of mesenchymal stem cells

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机构: [1]Division of Engineering in Medicine, Department of Medicine, Harvard Medical School, and Brigham and Women’s Hospital, Cambridge, MA, 02139, USA [2]Department of Biology, College of Arts and Sciences, Khalifa University (Main Campus), Abu Dhabi, P.O. Box, 127788, United Arab Emirates [3]Advanced Materials Chemistry Center (AMCC), Khalifa University (SAN Campus), Abu Dhabi, P.O. Box, 127788, United Arab Emirates [4]Leijten Lab, Department of Developmental Bioengineering, Faculty of Science and Technology, TechMed Centre, University Twente, Enschede, 7522 NB, the Netherlands [5]Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02139, USA [6]Department of Medicine, Harvard Medical School, and Brigham and Women’s Hospital, Boston, MA, 02115, USA [7]Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, 02115, USA [8]Division of Bioengineering, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea [9]Department of Biomedical Engineering, University of Illinois Chicago, Chicago, IL, 60612, USA [10]Departments of Orthopaedic Surgery, Pharmacology and Regenerative Medicine, and Mechanical and Industrial Engineering, University of Illinois Chicago, Chicago, IL, [11]Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China [12]Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China
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关键词: Oxygenating materials Stem cell fate Osteogenesis Tissue engineering Bone formation

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Oxygenating biomaterials can alleviate anoxic stress, stimulate vascularization, and improve engraftment of cellularized implants. However, the effects of oxygen-generating materials on tissue formation have remained largely unknown. Here, we investigate the impact of calcium peroxide (CPO)-based oxygen-generating microparticles (OMPs) on the osteogenic fate of human mesenchymal stem cells (hMSCs) under a severely oxygen deficient microenvironment. To this end, CPO is microencapsulated in polycaprolactone to generate OMPs with prolonged oxygen release. Gelatin methacryloyl (GelMA) hydrogels containing osteogenesis-inducing silicate nanoparticles (SNP hydrogels), OMPs (OMP hydrogels), or both SNP and OMP (SNP/OMP hydrogels) are engineered to comparatively study their effect on the osteogenic fate of hMSCs. OMP hydrogels associate with improved osteogenic differentiation under both normoxic and anoxic conditions. Bulk mRNAseq analyses suggest that OMP hydrogels under anoxia regulate osteogenic differentiation pathways more strongly than SNP/OMP or SNP hydrogels under either anoxia or normoxia. Subcutaneous implantations reveal a stronger host cell invasion in SNP hydrogels, resulting in increased vasculogenesis. Furthermore, time-dependent expression of different osteogenic factors reveals progressive differentiation of hMSCs in OMP, SNP, and SNP/OMP hydrogels. Our work demonstrates that endowing hydrogels with OMPs can induce, improve, and steer the formation of functional engineered living tissues, which holds potential for numerous biomedical applications, including tissue regeneration and organ replacement therapy.Copyright © 2023 Elsevier Ltd. All rights reserved.

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出版当年[2023]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
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第一作者机构: [1]Division of Engineering in Medicine, Department of Medicine, Harvard Medical School, and Brigham and Women’s Hospital, Cambridge, MA, 02139, USA [2]Department of Biology, College of Arts and Sciences, Khalifa University (Main Campus), Abu Dhabi, P.O. Box, 127788, United Arab Emirates [3]Advanced Materials Chemistry Center (AMCC), Khalifa University (SAN Campus), Abu Dhabi, P.O. Box, 127788, United Arab Emirates
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