IntroductionWe have developed an implant-type tissue-engineered cartilage using a poly-l-lactide scaffold. In a clinical study, it was inserted into subcutaneous areas of nasal dorsum in three patients, to correct cleft lip–nose deformity. The aim of this study was to helping evaluation on the efficacy of the regenerative cartilage.Methods3D data of nasal shapes were compared between before and after surgery in computed tomography (CT) images. Morphological and qualitative changes of transplants in the body were also evaluated on MRI, for one year.ResultsThe 3D data from CT images showed effective augmentation (>2 mm) of nasal dorsum in almost whole length, observed on the medial line of faces. It was maintained by 1 year post-surgery in all patients, while affected curves of nasal dorsum was not detected throughout the observation period. In magnetic resonance imaging (MRI), the images of transplanted cartilage had been observed until 1 year post-surgery. Those images were seemingly not straight when viewed from the longitudinal plain, and may have shown gentle adaptation to the surrounding nasal bones and alar cartilage tissues.ConclusionThose findings suggested the potential efficacy of this cartilage on improvement of cleft lip–nose deformity. A clinical trial is now being performed for industrialization.

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To disclose the influence of foreign body responses raised against a non-absorbable hydrogel consisting of tissue-engineered cartilage, we embedded human/canine chondrocytes within agarose and transplanted them into subcutaneous pockets in nude mice and donor beagles. One month after transplantation, cartilage formation was observed in the experiments using human chondrocytes in nude mice. No significant invasion of blood cells was noted in the areas where the cartilage was newly formed. Around the tissue-engineered cartilage, agarose fragments, a dense fibrous connective tissue and many macrophages were observed. On the other hand, no cartilage tissue was detected in the autologous transplantation of canine chondrocytes. Few surviving chondrocytes were observed in the agarose and no accumulation of blood cells was observed in the inner parts of the transplants. Localizations of IgG and complements were noted in areas of agarose, and also in the devitalized cells embedded within the agarose. Even if we had inhibited the proximity of the blood cells to the transplanted cells, the survival of the cells could not be secured. We suggest that these cytotoxic mechanisms seem to be associated not only with macrophages but also with soluble factors, including antibodies and complements.

Recently, there have been remarkable advances in regenerative medicine, and almost all disorders of the oral and maxillofacial region could be research targets of regenerative medicine. Meanwhile, treatment in this region has been well established using biomaterials, prostheses, and microsurgery. Therefore, to surpass such a conventional approach as an alternative, regenerative medicine should take an approach of being less invasive and/or more effective. In this report, we present our preclinical and clinical research on bone and cartilage regenerative medicine in the oral and maxillofacial region. Regarding bone regenerative medicine, we have tried to develop artificial bone that would maximize bone formation at the transplanted site, but would subsequently be replaced by autologous bone. We have made custom‐made artificial bone (CT‐Bone) using alpha‐tricalcium phosphate (α‐TCP) particles and an ink‐jet printer, and have conducted clinical research and trials on 30 patients. To develop tissue‐engineered cartilage with proper three‐dimensional (3D) morphological form and mechanical strength, we have optimized the culture medium of chondrocytes and the scaffold. Following a preclinical study confirming efficacy and safety, we have conducted clinical research in three patients with nasal deformity associated with cleft lip and palate, and are now starting multicenter clinical research.