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Abstract
Biomimetic bone tissue engineering strategies partially recapitulate development. We recently showed functional restoration of femoral defects using scaffold-free human mesenchymal stem cell (hMSC) condensates featuring localized morphogen presentation with delayed in vivo mechanical loading. Possible effects of construct geometry on healing outcome remain unclear. Here, we hypothesized that localized presentation of transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2 to engineered hMSC tubes mimicking femoral diaphyses induces endochondral ossification, and that TGF-β1 + BMP-2-presenting hMSC tubes enhance defect healing with delayed in vivo loading vs. loosely packed hMSC sheets. Localized morphogen presentation stimulated chondrogenic priming/endochondral differentiation in vitro. Subcutaneously, hMSC tubes formed cartilage templates that underwent bony remodeling. Orthotopically, hMSC tubes stimulated more robust endochondral defect healing vs. hMSC sheets. Tissue resembling normal growth plate was observed with negligible ectopic bone. This study demonstrates interactions between hMSC condensation geometry, morphogen bioavailability, and mechanical cues to recapitulate development for biomimetic bone tissue engineering.
Herberg et al. previously showed functional healing of femoral defects using scaffold-free human mesenchymal stem cell (hMSC) condensates with localized morphogen presentation. In this study, they report the importance of the tubular geometry of MSC condensates in long bone regeneration. Unlike loosely packed hMSC sheets, only hMSC tubes induced regenerate tissue partially resembling normal growth plate.
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1 Case Western Reserve University, Department of Biomedical Engineering, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847); SUNY Upstate Medical University, Departments of Ophthalmology and Visual Sciences, Cell and Developmental Biology, and Biochemistry and Molecular Biology, Syracuse, USA (GRID:grid.411023.5) (ISNI:0000 0000 9159 4457)
2 Case Western Reserve University, Department of Biomedical Engineering, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847)
3 University of Notre Dame, Department of Aerospace and Mechanical Engineering, Notre Dame, USA (GRID:grid.131063.6) (ISNI:0000 0001 2168 0066); University of Pennsylvania, Departments of Orthopaedic Surgery and Bioengineering, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
4 Worcester Polytechnic Institute, Department of Biomedical Engineering, Worcester, USA (GRID:grid.268323.e) (ISNI:0000 0001 1957 0327)
5 Case Western Reserve University, Department of Biomedical Engineering, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847); Case Western Reserve University, Department of Orthopaedic Surgery, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847); Case Western Reserve University, National Center for Regenerative Medicine, Division of General Medical Sciences, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847); University of Illinois, Departments of Biomedical Engineering, Pharmacology, Orthopedics, and Mechanical & Industrial Engineering, Chicago, USA (GRID:grid.185648.6) (ISNI:0000 0001 2175 0319)