신수련 (Harvard Medical School/Brigham and Women’s Hospital) | 한빛사논문 > 한빛사

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조회476

Harvard Medical School/Brigham and Women’s Hospital

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Biomaterials, 2023 May 31;300:12217 | https://doi.org/10.1016/j.biomaterials.2023.122179 Self-oxygenation of engineered living tissues orchestrates osteogenic commitment of mesenchymal stem cells

Shabir Hassan ^a,b,c,1, Ting Wang ^a,l,1, Kun Shi ^a,k,1, Yike Huang^a, Maria Elizabeth Urbina Lopez ^a, Kaifeng Gan ^a, Mo Chen^a, Niels Willemen ^a,d, Haroon Kalam^e, Eder Luna-Ceron ^a, Berivan Cecen^a, Gihan Daw Elbait ^b, Jinghang Li ^a, Luis Enrique Garcia-Rivera ^a, Melvin Gurian ^d, Mudassir Meraj Banday ^f, Kisuk Yang ^g,h, Myung Chul Lee ^a, Weida Zhuang^a, Castro Johnbosco ^d, Oju Jeonⁱ, Eben Alsberg ^i,j, Jeroen Leijten ^d, Su Ryon Shin^a

^aDivision of Engineering in Medicine, Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Cambridge, MA, 02139, USA
^bDepartment of Biology, College of Arts and Sciences, Khalifa University (Main Campus), Abu Dhabi, P.O. Box, 127788, United Arab Emirates
^cAdvanced Materials Chemistry Center (AMCC), Khalifa University (SAN Campus), Abu Dhabi, P.O. Box, 127788, United Arab Emirates
^dLeijten Lab, Department of Developmental Bioengineering, Faculty of Science and Technology, TechMed Centre, University Twente, Enschede, 7522 NB, the Netherlands
^eInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02139, USA
^fDepartment of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, 02115, USA
^gCenter for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA
^hDivision of Bioengineering, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea
ⁱDepartment of Biomedical Engineering, University of Illinois Chicago, Chicago, IL, 60612, USA
^jDepartments of Orthopaedic Surgery, Pharmacology and Regenerative Medicine, and Mechanical and Industrial Engineering, University of Illinois Chicago, Chicago, IL, 60612, USA
^kDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
^lDepartment of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China

¹These authors contributed equally to this work.
Corresponding authors: Jeroen Leijten, Su Ryon Shin

Abstract

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.

논문정보

형식Research article
게재일2023년 05월 (BRIC 등록일 2023-06-27)
연구진국내+국외 연구진
분야 바이오·의료융합 > 바이오소재

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