Self-oxygenation of engineered living tissues orchestrates osteogenic commitment of mesenchymal stem cells

Shabir Hassan, Ting Wang, Kun Shi, Yike Huang, Maria Elizabeth Urbina Lopez, Kaifeng Gan, Mo Chen, Niels Willemen, Haroon Kalam, Eder Luna-Ceron, Berivan Cecen, Gihan Daw Elbait, Jinghang Li, Luis Enrique Garcia-Rivera, Melvin Gurian, Mudassir Meraj Banday, Kisuk Yang, Myung Chul Lee, Weida Zhuang, Castro JohnboscoOju Jeon, Eben Alsberg, Jeroen Leijten*, Su Ryon Shin*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
13 Downloads (Pure)


Oxygenating biomaterials can alleviate anoxic stress, stimulate vascularization, and improve engraftment of cellularized implants. However, the effects of oxygen-generating materials on tissue formation have remained largely unknown. Here, we investigate the impact of calcium peroxide (CPO)-based oxygen-generating microparticles (OMPs) on the osteogenic fate of human mesenchymal stem cells (hMSCs) under a severely oxygen deficient microenvironment. To this end, CPO is microencapsulated in polycaprolactone to generate OMPs with prolonged oxygen release. Gelatin methacryloyl (GelMA) hydrogels containing osteogenesis-inducing silicate nanoparticles (SNP hydrogels), OMPs (OMP hydrogels), or both SNP and OMP (SNP/OMP hydrogels) are engineered to comparatively study their effect on the osteogenic fate of hMSCs. OMP hydrogels associate with improved osteogenic differentiation under both normoxic and anoxic conditions. Bulk mRNAseq analyses suggest that OMP hydrogels under anoxia regulate osteogenic differentiation pathways more strongly than SNP/OMP or SNP hydrogels under either anoxia or normoxia. Subcutaneous implantations reveal a stronger host cell invasion in SNP hydrogels, resulting in increased vasculogenesis. Furthermore, time-dependent expression of different osteogenic factors reveals progressive differentiation of hMSCs in OMP, SNP, and SNP/OMP hydrogels. Our work demonstrates that endowing hydrogels with OMPs can induce, improve, and steer the formation of functional engineered living tissues, which holds potential for numerous biomedical applications, including tissue regeneration and organ replacement therapy.

Original languageEnglish
Article number122179
Early online date31 May 2023
Publication statusPublished - Sept 2023


  • Bone formation
  • Osteogenesis
  • Oxygenating materials
  • Stem cell fate
  • Tissue engineering
  • 2023 OA procedure


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