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Engineered cartilage heals skull defects

Lan Doan, Connor Kelley, Heather Luong, Jeryl English, Hector Gomez, Evan Johnson, Dianna Cody,

and Pauline Jackie Duke

Houston, Tex

Introduction: The purposes of this study were todifferentiate embryonic limb bud cells into cartilage,characterize the nodules produced, and determine theirability to heal a mouse skull defect.

Methods: Aggregated mouse limb bud cells (E12-E12.5), cultured in a bioreactor for 3 weeks, were ana-lyzed by histology or implanted in 6 skull defects. Sixcontrols had no implants. The mice were scanned withmicrocomputed tomography weekly. At 2 and 4 weeks,a mouse from each group was killed, and the defectregion was prepared for histology.

Results: Chondrocytes in nodules were mainly hy-pertrophic. About 90% of the nodules mineralized.BrdU staining showed dividing cells in the perichon-drium. Microcomputed tomography scans showed in-creasing mineral in implanted nodules that completelyfilled the defect by 6 weeks; defects in the controlmice were not healed by then. At 2 and 4 weeks, the con-trol skull sections showed only a thin bony layer overthe defect. At 2 weeks, bone and cartilage filled thedefects with implants, and the implants were wellintegrated with the adjacent cortical bone. At 4 weeks,the implant had turned almost entirely into bone.

Conclusions: Cartilage differentiated in the biore-actor and facilitated healing when implanted into a de-fect. Engineering cartilage to replace bone is analternative to current methods of bone grafting.

Read the full text online at: www.ajodo.org,pages 162.e1-162.e9.

Am J Orthod Dentofacial Orthop 2010;137:162-3

0889-5406/$36.00

Copyright � 2010 by the American Association of Orthodontists.

doi:10.1016/j.ajodo.2009.10.001

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EDITOR’S SUMMARY

Reasons for autogenous bone grafting are now al-most too numerous to mention. In the final stages oftreating cleft lip and palate patients, grafts might beneeded in the cleft area before the placement of im-plants, or to close an oronasal fistula, for proper bonysupport next to the cleft, or even for increased supportfor the alar base. In implant dentistry, ridge augmenta-tion is frequently needed to improve the functionaland esthetic outcome of the implant. In other patients,a deficient alveolar ridge can affect phonetics and es-thetics. I could go on, but why? You would think thisstudy was as important as stem cell research. Well,that’s what it’s all about. This study confirms previousresults showing that engineered bone-forming cartilageis an excellent way to heal even membranous bone.

These authors investigated using in-vitro-differenti-ated cartilage—the bone-forming kind—to facilitate thehealing of skull defects in mice. The aim was to assesshistologically the stage and amount of cartilage pro-duced after 3 weeks of culture. This was evaluatedwith microcomputed tomography scanning and histol-ogy, noting the ability of cartilaginous spheroids usedto heal a defect in a membranous bone. The authors con-cluded that engineering cartilage could be an alternativemethod to repair the defect of a membranous bone.

The details of the study are published online andwill be of special interest to those with a backgroundin histology. Noted the authors, ‘‘Human bone-marrowstem cells will be used next to form cartilage in culture,so that we can proceed toward the goal of providing im-plants to patients constructed from their own stemcells.’’ With this type of basic research in our universi-ties, the future looks a little brighter.

Fig 1. Left, section of cartilage nodule stained with the von Kossa method; right, overlay showinghow the area of mineralization was calculated.

American Journal of Orthodontics and Dentofacial Orthopedics Doan et al 163Volume 137, Number 2

Q & ATurpin: Your approach to tissue engineering hasbeen called ‘‘a change in paradigm.’’ Why?

Doan: The current paradigm for engineering boneis to use bone cells and a scaffold, with addedgrowth factors. We use cartilage cells that maketheir own scaffolding and growth factors, which in-tegrate extremely well into the surrounding boneand are totally replaced during the endochondralprocess.

Turpin: This was the topic of your master’s degreethesis. How do you plan to make use of this researchexperience in the future?

Doan: My part of this project was to show that mes-enchymal cells differentiated into cartilage can healbone. The next step in the laboratory will be to differ-entiate human bone-marrow stem cells into cartilage.The research project will have broad implications;

the ability to repair bony defects in humans with theirown cells will change dentistry.

Turpin: Do you see the use of human stem cellsbecoming commonplace in craniofacial treatmentyears from now?

Doan: With the positive results of our project and thecurrent advances in stem-cell research, the possibil-ity of using them to replace bone in craniofacialfacial defects is promising. And it will not be somany years from now.

Turpin: Is the public cognizant of the varied rolesorthodontists play in the overall care of craniofacialpatients?

Doan: The public, for the most part, is probablyunaware that orthodontists are important membersof craniofacial teams that treat patients with cranio-facial defects.