The Journal of Bone and Joint Surgery (American). 2005;87:936-944.
doi:10.2106/JBJS.D.02104
© 2005 The Journal of Bone and Joint Surgery, Inc.
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Tissue-Engineered Osteochondral Constructs in the Shape of an Articular Condyle

Adel Alhadlaq, BDS, MS, PhD1 and Jeremy J. Mao, DDS, PhD1

1 Departments of Anatomy and Cell Biology, Bioengineering, and Orthodontics, Tissue Engineering Laboratory, MC 841, University of Illinois at Chicago, 801 South Paulina Street, Chicago, IL 60612. E-mail address for J.J. Mao: jmao2{at}uic.edu

Investigation performed at the Departments of Anatomy and Cell Biology, Bioengineering, and Orthodontics, University of Illinois at Chicago, Chicago, Illinois

In support of their research or preparation of this manuscript, one or more of the authors received grants or outside funding from the National Institutes of Health (grants R01DE13964 and R01DE15391), the National Institute of Dental and Craniofacial Research, and the National Institute of Biomedical Imaging and Bioengineering (R01EB02332). None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: An entire articular condyle engineered from stem cells may provide an alternative therapeutic approach to total joint replacement. This study describes our continuing effort to optimize the chondrogenic and osteogenic differentiation from mesenchymal stem cells toward engineering articular condyles in vivo.

Methods: Primary rat bone-marrow mesenchymal stem cells were induced to differentiate into chondrogenic and osteogenic lineages in vitro and were suspended in polyethylene glycol-based hydrogel. The hydrogel cell suspensions, each at a density of 20 x 106 cells/mL, were stratified into two separate layers that were molded into the shape and dimensions of an adult human cadaveric mandibular condyle by sequential photopolymerization. The osteochondral constructs fabricated in vitro were implanted in the dorsum of immunodeficient mice for twelve weeks.

Results: De novo formation of articular condyles in the shape and dimensions of the adult human mandibular condyle occurred after a twelve-week period of in vivo implantation. Histological evaluation demonstrated two stratified layers of cartilaginous and osseous tissues, and yet there was mutual infiltration of cartilage-like and bone-like tissues into each other's territories. The cartilaginous portion was stained intensively to safranin O and expressed immunolocalized type-II collagen. Chondrocytes adjacent to the tissue-engineered osteochondral junction were enlarged and expressed type-X collagen, typical of hypertrophic chondrocytes. The osseous portion contained bone trabeculae-like structures and expressed immunolocalized type-I collagen, osteopontin, and osteonectin.

Conclusions: A cell encapsulation density of 20 million cells/mL with in vivo incubation for twelve weeks yields further tissue maturation and phenotypic growth of both cartilage-like and bone-like tissues in the tissue-engineered articular condyle.

Clinical Relevance: Tissue engineering of an entire condyle with chondral and osseous components derived from a single population of adult stem cells, as described in the present study, may have therapeutic implications in total joint replacement.


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