3D-printed oxygen-releasing scaffolds improve bone regeneration in mice

Ashley L. Farris, Dennis Lambrechts, Yuxiao Zhou, Nicholas Y. Zhang, Naboneeta Sarkar, Megan C. Moorer, Alexandra N. Rindone, Ethan L. Nyberg, Alexander Perdomo-Pantoja, S. J. Burris, Kendall Free, Timothy F. Witham, Ryan C. Riddle, Warren L. Grayson

Research output: Contribution to journalArticlepeer-review


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 languageEnglish (US)
Article number121318
StatePublished - Jan 2022


  • 3D-printing
  • Adipose-derived stem cells
  • Bone tissue engineering
  • Microtanks
  • Osteogenesis
  • Oxygen delivery

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials


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