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A Native Bioactive Interface Functionalized with Osteoprogenitor Stem Cell-Derived Migrasomes for Enhanced Bone

Hongming Zhang1, Jiajia Wang1, Rong Yang1

  • 1Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, China.

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This study introduces migrasomes, released by bone stem cells, as a novel, cell-free approach for bone regeneration. Functionalized scaffolds with these migrasomes significantly enhanced bone repair in preclinical models.

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Cell Biology

Background:

  • Large bone defect regeneration is challenging due to insufficient osteoinductive signals.
  • Current cell-free bone regeneration methods using extracellular vesicles face purification and scaffold integration hurdles.
  • Migrasomes, extracellular matrix-affine organelles, offer a novel, underexplored potential for tissue engineering.

Purpose of the Study:

  • To develop a cell-free strategy for bone regeneration using migrasomes.
  • To create a functional osteoinductive interface by leveraging migrasome deposition from osteoprogenitor stem cells (OPSCs).
  • To evaluate the efficacy of migrasome-functionalized scaffolds in promoting bone regeneration.

Main Methods:

  • Human cortical bone-derived OPSCs were cultured and induced osteogenically to promote migrasome and calcium deposition.
  • OPSCs were seeded onto biphasic calcium phosphate (BCP) scaffolds, mineralized, and then decellularized to preserve the native migrasome layer.
  • Migrasome-functionalized scaffolds were assessed for osteogenic gene expression and tested in a murine calvarial defect model.

Main Results:

  • An in situ deposition strategy successfully created a native, osteogenic migrasome layer on BCP scaffolds without complex purification.
  • Migrasome-functionalized scaffolds significantly upregulated osteogenic gene expression compared to controls.
  • The scaffolds promoted substantial bone regeneration in a murine calvarial defect model.

Conclusions:

  • Migrasomes serve as a potent, endogenous signaling platform for effective cell-free bone tissue engineering.
  • This novel paradigm captures cellular secretomes for permanent biomaterial function, advancing regenerative medicine.
  • The developed method offers a promising new frontier for directing tissue repair through cell-free biomaterials.