Journal
BIOMATERIALS
Volume 280, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121318
Keywords
Osteogenesis; Bone tissue engineering; Oxygen delivery; 3D-printing; Adipose-derived stem cells; Microtanks
Funding
- National Science Foundation Graduate Research Fellowship (ALF)
- NIH National Institute for Arthritis and Musculoskeletal and Skin Diseases [1 F31 AR075368]
- NIH National Institute for Dental and Craniofacial Research Grant [5 R01 DE027957-02]
- Research Foundation - Flanders [12I6216 N, 1516517 N, V437017 N]
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Oxygen delivery plays a crucial role in enhancing the therapeutic efficacy of cell transplants. In this study, researchers developed a novel scaffold material that effectively releases oxygen, leading to improved bone tissue regeneration mediated by adipose-derived stem cells.
Low oxygen (O-2) diffusion into large tissue engineered scaffolds hinders the therapeutic efficacy of transplanted cells. To overcome this, we previously studied hollow, hyperbarically-loaded microtanks (mu tanks) to serve as O-2 reservoirs. To adapt these for bone regeneration, we fabricated biodegradable mu tanks from polyvinyl alcohol and poly (lactic-co-glycolic acid) and embedded them to form 3D-printed, porous poly-epsilon-caprolactone (PCL)-mu tank scaffolds. PCL-mu tank scaffolds were loaded with pure O-2 at 300-500 psi. When placed at atmospheric pressures, the scaffolds released O-2 over a period of up to 8 h. We confirmed the inhibitory effects of hypoxia on the osteogenic differentiation of human adipose-derived stem cells (hASCs and we validated that mu tank-mediated transient hyperoxia had no toxic impacts on hASCs, possibly due to upregulation of endogenous antioxidant regulator genes. We assessed bone regeneration in vivo by implanting O-2-loaded, hASC-seeded, PCL-mu tank scaffolds into murine calvarial defects (4 mm diameters x 0.6 mm height) and subcutaneously (4 mm diameter x 8 mm height). In both cases we observed increased deposition of extracellular matrix in the O-2 delivery group along with greater osteopontin coverages and higher mineral deposition. This study provides evidence that even short-term O-2 delivery from PCL-mu tank scaffolds may enhance hASC-mediated bone tissue regeneration.
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