Tissue-engineered autologous grafts for facial bone reconstruction.
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.
Department of Biomedical Engineering, Columbia University, 500 West 120th Street, New York, NY 10027, USA.
Sarindr
S
Bhumiratana
Department of Biomedical Engineering, Columbia University, 500 West 120th Street, New York, NY 10027, USA.
Jonathan C
JC
Bernhard
Division of Oral and Maxillofacial Surgery, Columbia University College of Dental Medicine, 630 West 168th Street, New York, NY 10032, USA.
David M
DM
Alfi
Department of Biomedical Engineering, Columbia University, 500 West 120th Street, New York, NY 10027, USA.
Keith
K
Yeager
Department of Biomedical Engineering, Columbia University, 500 West 120th Street, New York, NY 10027, USA.
Ryan E
RE
Eton
School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, LA 70803, USA.
Jonathan
J
Bova
LaCell LLC, 1441 Canal Street, New Orleans, LA 70112, USA.
Forum
F
Shah
LaCell LLC, 1441 Canal Street, New Orleans, LA 70112, USA. Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1324 Tulane Avenue, SL-99, New Orleans, LA 70112, USA.
Jeffrey M
JM
Gimble
School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, LA 70803, USA.
Mandi J
MJ
Lopez
Division of Oral and Maxillofacial Surgery, Columbia University College of Dental Medicine, 630 West 168th Street, New York, NY 10032, USA.
Sidney B
SB
Eisig
Department of Biomedical Engineering, Columbia University, 500 West 120th Street, New York, NY 10027, USA. gv2131@columbia.edu.
Gordana
G
Vunjak-Novakovic
D000818:Animals; D019149:Bioreactors; D002417:Cattle; D005147:Facial Bones / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds