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Dual-phase osteogenic and vasculogenic engineered tissue for bone formation.

Rameshwar R Rao1, Marina L Vigen, Alexis W Peterson

  • 1Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan.

Tissue Engineering. Part A
|September 18, 2014
PubMed
Summary

Injectable bone tissue engineering constructs show potential for orthopedic repair. Dual-phase constructs with osteogenic and vasculogenic components demonstrated ectopic bone formation, but also an inhibitory effect on vascularization.

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Tissue Engineering

Background:

  • Minimally invasive, injectable therapies are needed for orthopedic repair, especially for enhanced bone regeneration.
  • Developing dual-phase constructs can combine osteogenic and vasculogenic properties for improved bone healing.

Purpose of the Study:

  • To engineer a dual-phase injectable bone tissue construct with osteogenic and vasculogenic components.
  • To evaluate the in vivo performance of these constructs for neovasculature and ectopic bone formation.

Main Methods:

  • Created collagen/fibrin/hydroxyapatite hydrogel microbeads with human bone marrow-derived mesenchymal stem cells (bmMSC).
  • Predifferentiated microbeads toward osteogenic lineage and embedded them in a vasculogenic phase with bmMSC and human umbilical vein endothelial cells (HUVEC).
  • Assessed construct performance in vivo via subcutaneous injection into immunodeficient mice, using laser Doppler imaging and microcomputed tomography.

Main Results:

  • In vitro studies showed homogenous microbead dispersion and endothelial network formation.
  • In vivo, all constructs exhibited blood perfusion, with no significant differences in vessel density.
  • Significantly higher ectopic bone volume was observed in osteogenic-only constructs at 4 weeks.
  • At 8 weeks, osteogenic and blank groups showed higher bone volume than vasculogenic and dual-phase groups, suggesting an inhibitory effect of the vasculogenic component.

Conclusions:

  • Osteogenic microbeads can induce ectopic bone formation.
  • The inclusion of undifferentiated bmMSC and HUVEC in dual-phase constructs may inhibit bone formation.
  • This research offers insights for developing injectable therapies for enhanced vascularized bone tissue engineering.