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Vascularization of hollow channel-modified porous silk scaffolds with endothelial cells for tissue regeneration
Institution:1. Department of Biosciences and Bioengineering, Indian Istitute of Technology Guwahati, Guwahati 781039, India;2. Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, India;3. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, United States;4. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, United States;5. Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, United States;6. Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, United States;7. Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261, United States;8. Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, United States;9. Tissue Engineering Research Group (TERG), Royal College of Surgeons in Ireland (RCSI), Dublin D02 YN77, Ireland;1. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China;2. Department of Endodontics, Periodontics and Prosthodontics, University of Maryland Dental School, Baltimore, MD 21201, USA;3. Department of Orthopedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China;4. Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;5. Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA;6. Mechanical Engineering Department, University of Maryland, Baltimore County, MD 21250, USA;7. Temple University Kornberg School of Dentistry, 3223 North Broad Street, Philadelphia, PA 19140
Abstract:Despite the promise for stem cell-based tissue engineering for regenerative therapy, slow and insufficient vascularization of large tissue constructs negatively impacts the survival and function of these transplanted cells. A combination of channeled porous silk scaffolds and prevascularization with endothelial cells was investigated to test the ability of this tissue engineering strategy to support rapid and extensive vascularization process. We report that hollow channels promote in vitro prevascularization by facilitating endothelial cell growth, VEGF secretion, and capillary-like tube formation. When implanted in vivo, the pre-established vascular networks in the hollow channel scaffolds anastomose with host vessels and exhibit accelerated vascular infiltration throughout the whole tissue construct, which provides timely and sufficient nutrients to ensure the survival of the transplanted stem cells. This tissue engineering strategy can promote the effective application of stem cell-based regeneration to improve future clinical applications.
Keywords:Silk fibroin  Vascularization  Cell survival  Cell tracking  Regenerative medicine
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