TY - JOUR
T1 - Engineering anatomically shaped human bone grafts
AU - Grayson, Warren L.
AU - Fröhlich, Mirjam
AU - Yeager, Keith
AU - Bhumiratana, Sarindr
AU - Chan, M. Ete
AU - Cannizzaro, Christopher
AU - Wan, Leo Q.
AU - Liu, X. Sherry
AU - Guo, X. Edward
AU - Vunjak-Novakovic, Gordana
PY - 2010/2/23
Y1 - 2010/2/23
N2 - 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.
AB - 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.
KW - Biomimetic
KW - Bioreactor
KW - Craniofacial regeneration
KW - Mesenchymal stem cells
KW - Temporomandibular joint
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=77649269504&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649269504&partnerID=8YFLogxK
U2 - 10.1073/pnas.0905439106
DO - 10.1073/pnas.0905439106
M3 - Article
C2 - 19820164
AN - SCOPUS:77649269504
SN - 0027-8424
VL - 107
SP - 3299
EP - 3304
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -