title: Emulating native periosteum cell population and subsequent paracrine factor production to promote tissue engineered periosteum-mediated allograft healing.
abstract: Emulating autograft healing within the context of decellularized bone allografts has immediate clinical applications in the treatment of critical-sized bone defects. The periosteum, a thin, osteogenic tissue that surrounds bone, houses a heterogenous population of stem cells and osteoprogenitors. There is evidence that periosteum-cell derived paracrine factors, specifically vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), orchestrate autograft healing through host cell recruitment and subsequent tissue elaboration. In previous work, we demonstrated that the use of poly(ethylene glycol) (PEG) hydrogels as a tissue engineered (T.E.) periosteum to localize mesenchymal stem cells (MSCs) to the surface of decellularized bone enhances allograft healing and integration. Herein, we utilize a mixed population of 50:50 MSCs and osteoprogenitor cells to better mimic native periosteum cell population and paracrine factor production to further promote allograft healing. This mixed cell population was localized to the surface of decellularized allografts within degradable hydrogels and shown to expedite allograft healing. Specifically, bone callus formation and biomechanical graft-host integration are increased as compared to unmodified allografts. These results demonstrate the dual importance of periosteum-mediated paracrine factors orchestrating host cell recruitment as well as new bone formation while developing clinically translatable strategies for allograft healing and integration.
authors.affiliation: University of Rochester, Department of Biomedical Engineering, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA; University of Rochester Medical Center, Center for Musculoskeletal Research, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA. Electronic address: hoffman@bme.rochester.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hoffman
authors.affiliation: University of Rochester, Department of Biomedical Engineering, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA; University of Rochester Medical Center, Center for Musculoskeletal Research, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA; University of Rochester, Department of Chemical Engineering, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA; University of Rochester Medical Center, Department of Orthopaedics, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA. Electronic address: benoit@bme.rochester.edu.
authors.forename: Danielle S W
authors.initials: DS
authors.lastname: Benoit
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D016025:Bone Transplantation; D005260:Female; D005269:Femur / Q000473:pathology; D006085:Graft Survival; D020100:Hydrogels / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010012:Osteogenesis; D010521:Periosteum / Q000473:pathology* / Q000637:transplantation*; D011092:Polyethylene Glycols / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D020100:Hydrogels; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D011092:Polyethylene Glycols
keywords: Bone allografts; Cell transplantation; Hydrogels; Mesenchymal stem cells; Periosteum; Poly(ethylene glycol)
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