Abstract
Low oxygen (O2) diffusion into large tissue engineered scaffolds hinders the therapeutic efficacy of transplanted cells. To overcome this, we previously studied hollow, hyperbarically-loaded microtanks (μtanks) to serve as O2 reservoirs. To adapt these for bone regeneration, we fabricated biodegradable μtanks from polyvinyl alcohol and poly (lactic-co-glycolic acid) and embedded them to form 3D-printed, porous poly-ε-caprolactone (PCL)-μtank scaffolds. PCL-μtank scaffolds were loaded with pure O2 at 300–500 psi. When placed at atmospheric pressures, the scaffolds released O2 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 μtank-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 O2-loaded, hASC-seeded, PCL-μtank scaffolds into murine calvarial defects (4 mm diameters × 0.6 mm height) and subcutaneously (4 mm diameter × 8 mm height). In both cases we observed increased deposition of extracellular matrix in the O2 delivery group along with greater osteopontin coverages and higher mineral deposition. This study provides evidence that even short-term O2 delivery from PCL-μtank scaffolds may enhance hASC-mediated bone tissue regeneration.
Original language | English (US) |
---|---|
Article number | 121318 |
Journal | Biomaterials |
Volume | 280 |
DOIs | |
State | Published - Jan 2022 |
Keywords
- 3D-printing
- Adipose-derived stem cells
- Bone tissue engineering
- Microtanks
- Osteogenesis
- Oxygen delivery
ASJC Scopus subject areas
- Mechanics of Materials
- Ceramics and Composites
- Bioengineering
- Biophysics
- Biomaterials