TY - JOUR
T1 - Tissue-engineered autologous grafts for facial bone reconstruction
AU - Bhumiratana, Sarindr
AU - Bernhard, Jonathan C.
AU - Alfi, David M.
AU - Yeager, Keith
AU - Eton, Ryan E.
AU - Bova, Jonathan
AU - Shah, Forum
AU - Gimble, Jeffrey M.
AU - Lopez, Mandi J.
AU - Eisig, Sidney B.
AU - Vunjak-Novakovic, Gordana
N1 - Funding Information:
We gratefully acknowledge funding support by NIH (grants DE016525 and EB002520), the New York Partnership Bioaccelerate Program (CU11-1915), and Mikati Foundation (gift funding for research).
Publisher Copyright:
© 2016, American Association for the Advancement of Science. All rights reserved.
PY - 2016/6/15
Y1 - 2016/6/15
N2 - Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care - the use of bone harvested from another region in the body - has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, native bovine bone matrix, and a perfusion bioreactor for the growth and transport of living grafts, without bone morphogenetic proteins. The ramus-condyle unit, the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatán minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material and crafted it into an anatomically correct shape using image-guided micromilling to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either nonseeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering.
AB - Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care - the use of bone harvested from another region in the body - has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, native bovine bone matrix, and a perfusion bioreactor for the growth and transport of living grafts, without bone morphogenetic proteins. The ramus-condyle unit, the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatán minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material and crafted it into an anatomically correct shape using image-guided micromilling to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either nonseeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering.
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U2 - 10.1126/scitranslmed.aad5904
DO - 10.1126/scitranslmed.aad5904
M3 - Article
C2 - 27306665
AN - SCOPUS:84975062604
VL - 8
JO - Science translational medicine
JF - Science translational medicine
SN - 1946-6234
IS - 343
M1 - 343ra83
ER -