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Long-Term Comparison between Human Normal Conchal and Microtia Chondrocytes Regenerated by Tissue Engineering on Nanofiber Polyglycolic Acid Scaffolds

Nakao, Hitomi M.D., Ph.D.; Jacquet, Robin D. M.S.; Shasti, Mark M.D.; Isogai, Noritaka M.D., Ph.D.; Murthy, Ananth S. M.D.; Landis, William J. Ph.D.

Plastic and Reconstructive Surgery: April 2017 - Volume 139 - Issue 4 - p 911e–921e
doi: 10.1097/PRS.0000000000003201
Experimental: Original Articles

Background: Previous regeneration studies of auricle-shaped cartilage by tissue engineering leave unresolved whether the chondrocyte phenotype from human auricular chondrocytes seeded onto polymeric scaffolds is retained over the long term and whether microtia remnants may be a viable cell source for auricular reconstruction.

Methods: Chondrocytes were isolated from human ears, either normal conchal ear or microtia cartilage remnants, expanded in vitro, and seeded onto nanoscale-diameter polyglycolic acid sheets. These tissue-engineered constructs were implanted into athymic mice for up to 40 weeks. At harvest times of 5, 10, 20, and 40 weeks, samples were documented by gross morphology, histology, and reverse transcription-quantitative polymerase chain reaction analysis.

Results: Neocartilages generated from the two types of surgical tissues were similar in appearance of their extracellular matrices and positive staining for elastin and proteoglycans. In the 5- to 40-week time interval, there was an increasing trend in gene expression for type II collagen, elastin, and sex determining region Y box 5, important to normal cartilage phenotype, and a decreasing trend in gene expression for type III collagen, a fibroblast and dedifferentiation marker. Over 40 weeks of implantation, the original nanoscale-diameter polyglycolic acid scaffold dimensions (1 cm × 1 cm × 80 µm) were generally maintained in tissue-engineered cartilage length and width, and thickness was statistically significantly increased.

Conclusions: Auricular cartilage can be regenerated over the long term (40 weeks) from surgical remnants by tissue-engineering techniques incorporating nanoscale-diameter polyglycolic acid scaffolds. Based on the present assays, microtia neocartilage very closely resembles tissue-engineered cartilage regenerated from chondrocytes isolated from normal conchal cartilage.

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Osaka, Japan; Akron, Ohio; and Baltimore, Md.

From the Department of Plastic and Reconstructive Surgery, Kinki University Medical School, Osaka-sayama; the Department of Polymer Science, University of Akron; the Division of Plastic and Reconstructive Surgery, Akron Children’s Hospital; and the Department of Orthopaedics, University of Maryland School of Medicine.

Received for publication March 17, 2016; accepted August 2, 2016.

Presented in part at the 2013 Ohio Valley Society of Plastic Surgeons Annual Meeting, in Indianapolis, Indiana, May 17 through 19, 2013.

Disclosure: The Landis Laboratory (to W.J.L. and R.D.J.) at the University of Akron received financial support from Gunze Co., Ltd., Kyoto, Japan, the KLS-Martin Group, Muhlheim, Germany, and the Akron Children’s Hospital Foundation, Akron, Ohio (to A.S.M.) for research to study auricular reconstruction. Gunze Co., Ltd., also supplied the nanoscalediameter polyglycolic acid fabric used as a scaffold in these studies for generation of neocartilages. Dr. Noritaka Isogai has filed a U.S. patent with Gunze Co., Ltd., for the use of nanoscale-diameter polyglycolic acid in auricular tissue engineering. Drs. Hitomi Nakao and Mark Shasti have no financial interest to declare in relation to the content of this article.

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William J. Landis, Ph.D., Department of Polymer Science, Goodyear Polymer Center, Room 1201C, University of Akron, 170 University Avenue, Akron, Ohio 44325-3909,

©2017American Society of Plastic Surgeons