The use of a synthetic oxygen carrier-enriched hydrogel to enhance mesenchymal stem cell-based bone formation in vivo.
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.
Kimelman-Bleich
Nadav
N
Skeletal Biotech Lab, The Hebrew University of Jerusalem-Hadassah Medical Campus, Ein Kerem, Jerusalem 91120, Israel.
Pelled
Gadi
G
Sheyn
Dima
D
Kallai
Ilan
I
Zilberman
Yoram
Y
Mizrahi
Olga
O
Tal
Yamit
Y
Tawackoli
Wafa
W
Gazit
Zulma
Z
Gazit
Dan
D
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
D055396:Bone Morphogenetic Protein 2; D005466:Fluorocarbons; D020100:Hydrogels; D015675:Osteocalcin; C008807:perfluorotributylamine; D013752:Tetracycline; D010100:Oxygen