Millions of patients worldwide are affected by craniofacial deformations caused by congenital defects or trauma. Current surgical interventions have limited therapeutic outcomes; therefore, methods that would allow cartilage restoration are of great interest. A number of studies on embryonic limb development have shown that chondrogenesis is initiated by cellular condensation, during which mesenchymal progenitors aggregate and form 3D structures. Here, we demonstrated efficient regeneration of avascular elastic cartilage from in vitro-grown mesenchymal condensation, which recapitulated the early stages of chondrogenesis, including transient vascularization. After transplantation of vascularized condensed progenitors into immunodeficient mice, we used an intravital imaging approach to follow cartilage maturation. We determined that endothelial cells are present inside rudimentary cartilage (mesenchymal condensation) prior to cartilage maturation. Recreation of endothelial interactions in culture enabled a recently identified population of adult elastic cartilage progenitors to generate mesenchymal condensation in a self-driven manner, without requiring the support of exogenous inductive factors or scaffold materials. Moreover, the culture-grown 3D condensed adult-derived progenitors were amenable to storage via simple freezing methods and efficiently reconstructed 3D elastic cartilage upon transplantation. Together, our results indicate that transplantation of endothelialized and condensed progenitors represents a promising approach to realizing a regenerative medicine treatment for craniofacial deformations.

Background: In bilateral cleft lip and palate (BCLP) patients with protrusion and/or torsion of the premaxillae, it is difficult to achieve a good outcome. We have developed a series of procedures of premaxillary osteotomy with primary cheiloplasty for BCLP patients who did not respond well to presurgical orthodontics (PSO). Methods: A total of 27 BCLP patients with protrusion and/or torsion of the premaxillae underwent PSO. For 3 BCLP patients in whom the protruded premaxillae could not be returned to a good position, a primary premaxillary osteotomy and gingivoperiosteoplasty (GPP) with cheiloplasty were performed simultaneously. Subsequently, Furlow palatoplasty was performed by one and a half years of age. Maxillary growth was evaluated by dental occlusion at 4 years of age. Results: A premaxillary osteotomy and GPP with cheiloplasty were performed at 6 months. The patients’ facial structures improved, their premaxillae were positioned more superiorly, and normal inclination of the incisors was achieved. They had edge-to-edge occlusions or cross bites at 4 years of age. Conclusions: As advantages, the patients’ facial structures improved, and the alveolar bones were formed by GPP. As a disadvantage, premaxillary necrosis might occur because of poor blood circulation. It is important to secure the following 2 blood supplies: from the periosteum and soft-tissue of the anterior premaxillae and from the periosteum and mucosa of the nasal septum. Synchronous premaxillary osteotomy and GPP with primary cheiloplasty are appropriate when the premaxillae cannot be properly repositioned by PSO or PSO cannot be done.

A palatal fistula is a common complication of cleft palate repair. Although a buccal musculomucosal flap (BMMF) is effective for fistula repair, it does have the following problems: a second operation may be required to release the pedicle on the oral side and unilateral BMMF cannot close mucosal defects of both the nasal and oral sides. A novel fistula closure method using the folded BMMF (f-BMMF) invented by the authors is presented. A 8-year-old-boy with bilateral cleft lip and palate with anencephaly. A fistula in the hard palate occurred after palatoplasty by the Furlow method, and an f-BMMF was planned. The mucosal defects of the nasal and oral sides were covered by 2 separate islands of mucosal epithelium. Finally, no reoperation was needed to remove the pedicle of the f-BMMF. The f-BMMF is able to cover both sides without a raw surface and a mucosal graft even in cases of large fistula closure, although BMMF cannot usually cover both oral and nasal sides of a fistula. The advantages of this procedure are that it does not require second surgery to release the pedicle and that its distal island mucosa can be used to monitor engraftment. This proposed method seems to be an appealing alternative.

Morphologically stable scaffold-free elastic cartilage tissue is crucial for treating external ear abnormalities. However, establishing adequate mechanical strength is challenging, owing to the difficulty of achieving chondrogenic differentiation in vitro; thus, cartilage reconstruction is a complex task. Auricular perichondrial chondroprogenitor cells exhibit high proliferation potential and can be obtained with minimal invasion. Therefore, these cells are an ideal resource for elastic cartilage reconstruction. In this study, we aimed to develop a novel in vitro scaffold-free method for elastic cartilage reconstruction, using human auricular perichondrial chondroprogenitor cells. Inducing chondrogenesis by using microscopic spheroids similar to auricular hillocks significantly increased the chondrogenic potential. The size and elasticity of the tissue were maintained after craniofacial transplantation in immunodeficient mice, suggesting that the reconstructed tissue was morphologically stable. Our novel tissue reconstruction method may facilitate the development of future treatments for external ear abnormalities.

We have developed a modality of treatment of giant pigmented nevus of intradermal type. This method involves application of autologous cultured dermal substitute (CDS), followed by grafting of epidermis separated from the patient's nevus skin. To prepare the wound bed, autologous CDS was applied onto a full-thickness skin defect after complete excision of the nevus. The excised nevus skin was preserved for 1 week, after which the epidermis was separated from the nevus skin by enzymatic treatment with dispase. The epidermis thus obtained was grafted onto the resulting wound bed. This procedure was used to treat a giant pigmented nevus on a 7-year-old patient. The grafted region was soft with good tone 1 year after epidermis grafting. These results indicate that the present method can achieve complete excision of giant nevus, with esthetically acceptable results, although it requires careful monitoring for a long time.