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

doi:10.1016/j.biomaterials.2021.121318

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

Biomaterials. 2022 Jan:280:121318. doi: 10.1016/j.biomaterials.2021.121318. Epub 2021 Dec 11.

Affiliations

¹ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Baltimore Veterans Administration Medical Center, Baltimore, MD, USA.
³ Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁵ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: wgrayson@jhmi.edu.

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.

Keywords: 3D-printing; Adipose-derived stem cells; Bone tissue engineering; Microtanks; Osteogenesis; Oxygen delivery.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Regeneration
Cell Differentiation
Mice
Osteogenesis*
Oxygen / pharmacology
Polyesters / pharmacology
Printing, Three-Dimensional
Tissue Engineering*
Tissue Scaffolds

Substances

Polyesters
Oxygen

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding