BioEngineered personalized human bone grafts created from bone marrow stem cells

Scale up of engineered bone grafts towards clinical applications is always a central challenge in regenerative medicine. In latest article PNAS Grayson et. al report an approach to develop clinically sized viable bone grafts of human temporomandibular joint (TMJ) condylar or Jaw bone seeded with human bone marrow stem/progenitor cells (hMSCs). This study was carried out by a research group led by Dr Gordana Vunjak-Novakovic at the Columbia University and it appears in the online issue of journal PNAS. This is first time that anatomically shaped bone graft has been reported and this work has major implications. As these grafts are engineered from the patient’s own stem cells hence there is a low risk of graft rejection. This work opens door for many possible clinical applications such bone reconstructions after congenital defects, cancer resections, bone grafts for spinal fusion (also called arthrodesis) and many more. In following figure B is the a real jaw while C is the bioengineered one.

The whole approach is described below

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. Moreover, the density and architecture of bone matrix correlated with the intensity and pattern of the interstitial flow, as determined in experimental and modeling studies.

However the engineered graft does not replicate the whole system, for instance it does not include other tissues such as cartilage layer which is often damaged in TMJ disorders. Future challenges include engineering of vascularized bone that can be immediately connected to the blood supply of the host and hybrid grafts including bone and tissues.

Reference:
Grayson, W., Frohlich, M., Yeager, K., Bhumiratana, S., Chan, M., Cannizzaro, C., Wan, L., Liu, X., Guo, X., & Vunjak-Novakovic, G. (2009). Regenerative Medicine Special Feature: Engineering anatomically shaped human bone grafts Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0905439106