Journal of Clinical Trials
Open Access

Abstract

Implant-type Tissue-engineered Cartilage for Secondary Correction of Cleft Lip-nose Patients: An Exploratory First-in-human Trial

Kazuto Hoshi, Yuko Fujihara, Hideto Saijo, Yukiyo Asawa, Satoru Nishizawa, Sanshiro Kanazawa, Sakura Uto, Ryoko Inaki, Mariko Matsuyama, Tomoaki Sakamoto, Makoto Watanabe, Madoka Sugiyama, Kazumichi Yonenaga, Atsuhiko Hikita and Tsuyoshi Takato

Objective: Secondary correction of cleft lip-nose presents a formidable challenge in cleft lip and palate surgery. Although numerous approaches have been proposed, suitable graft materials cannot be obtained from any part of body or the artificial biomaterials. We have established implant-type tissue-engineered cartilage using a porous scaffold comprised of poly L-lactic acid. The aim of this study was to primarily assess the safety of the autologous tissue-engineered cartilage when used in the cleft lip-nose patients as an exploratory first-in-human trial, and to explore the usefulness of the cartilage.

Methods: After the acquisition of institutional and governmental permission, we used this implant-type tissueengineered cartilage for the treatment of three cleft lip-nose patients. We examined whether or not serious adverse events had occurred by which removal of the tissue-engineered cartilage was needed, 3 years after the transplantation. We also explored the usefulness of the cartilage, as aesthetic and functional outcomes.

Results: Each tissue-engineered cartilage fulfilled the defined release criteria for transplantation. The transplantation of the tissue-engineered cartilage in all the patients was performed just as planned. After 3 years of transplantation, we did not experience any serious adverse events that were related to the tissue-engineered cartilage. As a non-serious adverse event, calcification of the tissue-engineered cartilage was found in one patient. Nose shapes improved in all the patients, and more than 2 mm of nose augmentation maintained for 3 years postsurgery, as measured in cephalogram. Although the dysfunction in facial expression or playing sports had rather increased immediately after the transplantation, the inconvenience generally recovered or improved during the postsurgical course.

Conclusion: The implant-type tissue-engineered cartilage could safely reconstruct the nasal dorsum and apex of cleft lip-noses. This tissue-engineered cartilage possibly leads to effective correction of a severe cleft lip-nose deformity with aesthetic and functional improvement.