Spatiotemporal Immunomodulation Using Biomimetic Scaffold Promotes Endochondral Ossification-Mediated Bone Healing

Yutong Liu, Zhaogang Yang, Lixuan Wang, Lili Sun, Betty Y.S. Kim, Wen Jiang, Yuan Yuan, Changsheng Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Biomaterials play an important role in treating bone defects by promoting direct osteogenic healing through intramembranous ossification (IO). However, majority of the body's bones form via cartilaginous intermediates by endochondral ossification (EO), a process that has not been well mimicked by engineered scaffolds, thus limiting their clinical utility in treating large segmental bone defects. Here, by entrapping corticosteroid dexamethasone within biomimetic recombinant human bone morphogenetic protein (rhBMP)-loaded porous mesoporous bioglass scaffolds and regulating their release kinetics, significant degree of ectopic bone formation through endochondral ossification is achieved. By regulating the recruitment and polarization of immune suppressive macrophage phenotypes, the scaffold promotes rapid chondrogenesis by activating Hif-3α signaling pathway in mesenchymal stem cells, which upregulates the expression of downstream chondrogenic genes. Inhibition of Hif-3α signaling reverses the endochondral ossification phenotype. Together, these results reveal a strategy to facilitate developmental bone growth process using immune modulating biomimetic scaffolds, thus providing new opportunities for developing biomaterials capable of inducing natural tissue regeneration.

Original languageEnglish (US)
JournalAdvanced Science
DOIs
StateAccepted/In press - 2021

Keywords

  • dexamethasone
  • endochondral ossification
  • hypoxia signaling pathway
  • immunomodulation
  • sequential release

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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