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Craniofacial Tissue Engineering by Stem Cells

¹ Columbia University College of Dental Medicine and Biomedical Engineering, 630 W. 168 St. - PH7 CDM, New York, NY 10032, USA;
² Michigan Center for Oral Health Research, University of Michigan Clinical Research Center, 24 Frank Lloyd Wright Drive, Lobby M, Box 422, Ann Arbor, MI 48106;
³ Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Palo Alto, CA 94305;
⁴ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109;
⁵ Department of Biological and Materials Science, University of Michigan, 1011 N. University, Ann Arbor, MI 48109; and
⁶ National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 134, 30 Convent Dr. MSC 4320, Bethesda, MD 20892

View larger version (113K): [in this window] [in a new window]   Figure 1. Engineered neogenesis of human-shaped mandibular condyle from mesenchymal stem cells. (A) Harvested osteochondral construct retained the shape and dimension of the cadaver human mandibular condyle after in vivo implantation. Scale bar: 5 mm. (B) Von Kossa-stained section showing the interface between stratified chondral and osseous layers. Multiple mineralization nodules are present in the osseous layer (lower half of the photomicrograph), but absent in the chondral layer. (C) Positive safranin O staining of the chondrogenic layer indicates the synthesis of abundant glycosaminoglycans. (D) H&E-stained section of the osteogenic layer showing a representative osseous island-like structure consisting of MSC-differentiated osteoblast-like cells on the surface and in the center. Reproduced with permission from Biomedical Engineering Society.

View larger version (131K): [in this window] [in a new window]   Figure 2. Histologic and immunohistochemical characterization of a human-shaped mandibular condyle engineered from mesenchymal stem cells after in vivo implantation. (A) Representative photomicrograph showing positive safranin O staining of the upper cartilage layer, indicating the presence of abundant glycosaminoglycans. In contrast, the osseous portion shows negative safranin O staining. (B) Positive immunohistochemical localization of type II collagen in the cartilage portion. The osseous portion was negative to type II collagen immunolocalization. (C) Positive immunolocalization of osteopontin within the osseous portion. By contrast, the cartilage portion lacks osteopontin expression. (D) Representative micrograph of hydrogel control cell-free construct showing host fibrous-tissue capsule surrounding the construct, but a lack of host cell invasion. Reproduced with permission from Mary Ann Liebert.

View larger version (38K): [in this window] [in a new window]   Figure 3. Design and engineering of minipig mandibular condyle. (A) Original Computed Tomography (CT) scan of minipig mandible. (B) Image-based design of condyle scaffold. (C) PCL (polycaprolactone) degradable polymer scaffold fabricated with SLS (Selective Laser Sintering) attached to the ramus. (D) Regrowth of condyle following 3 months’ implantation (new condyle shown in red circle). (E) Comparison with normal condyle from contralateral side in Yucatan minipig.

View larger version (22K): [in this window] [in a new window]   Figure 4. Delivery approaches for periodontal bioengineering. Ex vivo gene therapy involves the harvesting of tissue biopsies, expansion of cell populations, genetic manipulations of cells, and subsequent transplantation to periodontal osseous defects (A), while the in vivo gene transfer approach involves the direct delivery of growth factor transgenes to the periodontal osseous defects (B).

View larger version (45K): [in this window] [in a new window]   Figure 5. Bone metabolic activity of animals implanted with control (no cells) or adipose-derived adult stromal (ADS) cell-seeded scaffolds, as determined by radiolabeled methylene diphosphonate incorporation overlaid with micro-CT images. For each time-point, the top row displays the micro-CT scan, the middle row displays the metabolic activity, and the lower row displays the overlaid composite of metabolic activity and micro-CT scan. For all columns at each time-point, the left column is the x axis, the middle column is the y axis, and the right column is the z axis. For orientation, we have marked the defect with a yellow arrow for the three views of the micro-CT image. The location of the defect does not change between 2 and 12 weeks. Bone scan intensity is indicated in color on the left axis of the image, with white and red indicating the highest value and black and blue indicating lowest value. This Fig. originally appeared in Cowan et al.(2004) and is reproduced here with permission from the Nature Publishing Group (http://www.nature.com/).

Journal of Dental Research, Vol. 85, No. 11, 966-979 (2006)
DOI: 10.1177/154405910608501101


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