Scaffold-free human mesenchymal stem cell construct geometry regulates long bone regeneration

Commun Biol. 2021 Jan 19;4(1):89. doi: 10.1038/s42003-020-01576-y.

Abstract

Biomimetic bone tissue engineering strategies partially recapitulate development. We recently showed functional restoration of femoral defects using scaffold-free human mesenchymal stem cell (hMSC) condensates featuring localized morphogen presentation with delayed in vivo mechanical loading. Possible effects of construct geometry on healing outcome remain unclear. Here, we hypothesized that localized presentation of transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2 to engineered hMSC tubes mimicking femoral diaphyses induces endochondral ossification, and that TGF-β1 + BMP-2-presenting hMSC tubes enhance defect healing with delayed in vivo loading vs. loosely packed hMSC sheets. Localized morphogen presentation stimulated chondrogenic priming/endochondral differentiation in vitro. Subcutaneously, hMSC tubes formed cartilage templates that underwent bony remodeling. Orthotopically, hMSC tubes stimulated more robust endochondral defect healing vs. hMSC sheets. Tissue resembling normal growth plate was observed with negligible ectopic bone. This study demonstrates interactions between hMSC condensation geometry, morphogen bioavailability, and mechanical cues to recapitulate development for biomimetic bone tissue engineering.

Publication types

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

MeSH terms

  • Biocompatible Materials
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Regeneration / physiology
  • Bone and Bones / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Chondrogenesis / drug effects
  • Collagen / metabolism
  • Humans
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Osteogenesis / physiology
  • Tissue Engineering
  • Transforming Growth Factor beta1 / metabolism
  • Wound Healing / drug effects

Substances

  • BMP2 protein, human
  • Biocompatible Materials
  • Bone Morphogenetic Protein 2
  • Transforming Growth Factor beta1
  • Collagen