Optimized cell survival and seeding efficiency for craniofacial tissue engineering using clinical stem cell therapy.
Traumatic injuries involving the face are very common, yet the clinical management of the resulting craniofacial deficiencies is challenging. These injuries are commonly associated with missing teeth, for which replacement is compromised due to inadequate jawbone support. Using cell therapy, we report the upper jaw reconstruction of a patient who lost teeth and 75% of the supporting jawbone following injury. A mixed population of bone marrow-derived autologous stem and progenitor cells was seeded onto β-tricalcium phosphate (β-TCP), which served as a scaffold to deliver cells directly to the defect. Conditions (temperature, incubation time) to achieve the highest cell survival and seeding efficiency were optimized. Four months after cell therapy, cone beam computed tomography and a bone biopsy were performed, and oral implants were placed to support an engineered dental prosthesis. Cell seeding efficiency (>81%) of the β-TCP and survival during the seeding process (94%) were highest when cells were incubated with β-TCP for 30 minutes, regardless of incubation temperature; however, at 1 hour, cell survival was highest when incubated at 4°C. Clinical, radiographic, and histological analyses confirmed that by 4 months, the cell therapy regenerated 80% of the original jawbone deficiency with vascularized, mineralized bone sufficient to stably place oral implants. Functional and aesthetic rehabilitation of the patient was successfully completed with installation of a dental prosthesis 6 months following implant placement. This proof-of-concept clinical report used an evidence-based approach for the cell transplantation protocol used and is the first to describe a cell therapy for craniofacial trauma reconstruction.
Department of Orthodontics and Pediatric Dentistry, Department of Periodontics and Oral Medicine, Department of Oral and Maxillofacial Surgery, Center for Oral Health Research, and Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Archana
A
Rajan
Department of Orthodontics and Pediatric Dentistry, Department of Periodontics and Oral Medicine, Department of Oral and Maxillofacial Surgery, Center for Oral Health Research, and Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Emily
E
Eubanks
Department of Orthodontics and Pediatric Dentistry, Department of Periodontics and Oral Medicine, Department of Oral and Maxillofacial Surgery, Center for Oral Health Research, and Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Sean
S
Edwards
Department of Orthodontics and Pediatric Dentistry, Department of Periodontics and Oral Medicine, Department of Oral and Maxillofacial Surgery, Center for Oral Health Research, and Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Sharon
S
Aronovich
Department of Orthodontics and Pediatric Dentistry, Department of Periodontics and Oral Medicine, Department of Oral and Maxillofacial Surgery, Center for Oral Health Research, and Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Suncica
S
Travan
Department of Orthodontics and Pediatric Dentistry, Department of Periodontics and Oral Medicine, Department of Oral and Maxillofacial Surgery, Center for Oral Health Research, and Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Ivan
I
Rudek
Department of Orthodontics and Pediatric Dentistry, Department of Periodontics and Oral Medicine, Department of Oral and Maxillofacial Surgery, Center for Oral Health Research, and Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Feng
F
Wang
Department of Orthodontics and Pediatric Dentistry, Department of Periodontics and Oral Medicine, Department of Oral and Maxillofacial Surgery, Center for Oral Health Research, and Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Alejandro
A
Lanis
Department of Orthodontics and Pediatric Dentistry, Department of Periodontics and Oral Medicine, Department of Oral and Maxillofacial Surgery, Center for Oral Health Research, and Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA dkaigler@umich.edu.
Darnell
D
Kaigler
D064592:Autografts; D001705:Bioprosthesis; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002130:Calcium Phosphates / Q000737:chemistry; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D017266:Dental Prosthesis; D005260:Female; D006801:Humans; D008437:Maxilla / Q000000981:diagnostic imaging / Q000293:injuries / Q000378:metabolism; D008875:Middle Aged; D010012:Osteogenesis; D011859:Radiography; D023822:Tissue Engineering; D054457:Tissue Scaffolds
D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate
Bone marrow; Bone regeneration; Cell therapy; Implants; Scaffold; Stem cells