Engineering anatomically shaped human bone grafts

Warren L. Grayson, Mirjam Fröhlich, Keith Yeager, Sarindr Bhumiratana, M. Ete Chan, Christopher Cannizzaro, Leo Q. Wan, X. Sherry Liu, X. Edward Guo, Gordana Vunjak-Novakovic

Research output: Contribution to journalArticlepeer-review

306 Scopus citations


The ability to engineer anatomically correct pieces of viable and functional human bone would have tremendous potential for bone reconstructions after congenital defects, cancer resections, and trauma.We report that clinically sized, anatomically shaped, viable human bone grafts can be engineered by using human mesenchymal stem cells (hMSCs) and a "biomimetic" scaffold-bioreactor system. We selected the temporomandibular joint (TMJ) condylar bone as our tissue model, because of its clinical importance and the challenges associated with its complex shape. Anatomically shaped scaffolds were generated from fully decellularized trabecular bone by using digitized clinical images, seeded with hMSCs, and cultured with interstitial flow of culture medium. A bioreactor with a chamber in the exact shape of a human TMJ was designed for controllable perfusion throughout the engineered construct. By 5 weeks of cultivation, tissue growth was evidenced by the formation of confluent layers of lamellar bone (by scanning electron microscopy), markedly increased volume of mineralized matrix (by quantitative microcomputer tomography), and the formation of osteoids (histologically). Within bone grafts of this size and complexity cells were fully viable at a physiologic density, likely an important factor of graft function. Moreo-ver, the density and architecture of bone matrix correlated with the intensity and pattern of the interstitial flow, as determined in experimental and modeling studies. This approach has potential to overcome a critical hurdle - in vitro cultivation of viable bone grafts of complex geometries - to provide patient-specific bone grafts for craniofacial and orthopedic reconstructions.

Original languageEnglish (US)
Pages (from-to)3299-3304
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Feb 23 2010
Externally publishedYes


  • Biomimetic
  • Bioreactor
  • Craniofacial regeneration
  • Mesenchymal stem cells
  • Temporomandibular joint
  • Tissue engineering

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Engineering anatomically shaped human bone grafts'. Together they form a unique fingerprint.

Cite this