title: The use of a synthetic oxygen carrier-enriched hydrogel to enhance mesenchymal stem cell-based bone formation in vivo.
abstract: A major hurdle to surmount in bone-tissue engineering is ensuring a sufficient oxygen supply to newly forming tissue to avoid cell death or delayed development of osteogenic features. We hypothesized that an oxygen-enriched hydrogel scaffold would enhance tissue-engineered bone formation in vivo. To test this, we used a well-characterized mesenchymal stem cell (MSC) line, Tet-off BMP2 MSC, whose cells were engineered to express recombinant human bone morphogenetic protein-2. Cells were suspended in hydrogel supplemented with perfluorotributylamine (PFTBA) and implanted subcutaneously in an ectopic site, a radial bone defect, or a lumbar paravertebral muscle (mouse model of spinal fusion) in C3H/HeN mice. For controls, we used cells suspended in the same gel without PFTBA. In the ectopic site, there were significant increases in bone formation (2.5-fold increase), cell survival, and osteocalcin activity in the PFTBA-supplemented groups. PFTBA supplementation significantly increased structural parameters of bone in radial bone defects and triggered a significant 1.4-fold increase in bone volume in the spinal fusion model. We conclude that synthetic oxygen carrier supplementation of tissue-engineered implants enhances ectopic bone formation and yields better bone quality and volume in bone-repair and spinal fusion models, probably due to increased cell survival.
authors.affiliation: Skeletal Biotech Lab, The Hebrew University of Jerusalem-Hadassah Medical Campus, Ein Kerem, Jerusalem 91120, Israel.
authors.forename: Nadav
authors.initials: N
authors.lastname: Kimelman-Bleich
authors.forename: Gadi
authors.initials: G
authors.lastname: Pelled
authors.forename: Dima
authors.initials: D
authors.lastname: Sheyn
authors.forename: Ilan
authors.initials: I
authors.lastname: Kallai
authors.forename: Yoram
authors.initials: Y
authors.lastname: Zilberman
authors.forename: Olga
authors.initials: O
authors.lastname: Mizrahi
authors.forename: Yamit
authors.initials: Y
authors.lastname: Tal
authors.forename: Wafa
authors.initials: W
authors.lastname: Tawackoli
authors.forename: Zulma
authors.initials: Z
authors.lastname: Gazit
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005466:Fluorocarbons / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D020007:Implants, Experimental; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects; D011884:Radius / Q000187:drug effects / Q000473:pathology; D013123:Spinal Fusion; D013752:Tetracycline / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D005466:Fluorocarbons; D020100:Hydrogels; D015675:Osteocalcin; C008807:perfluorotributylamine; D013752:Tetracycline; D010100:Oxygen