RESUMO
BACKGROUND: Upon orthognathic mandibular advancement surgery the adjacent soft tissues can displace the distal bone segment and increase the load on the temporomandibular joint causing loss of its integrity. Remodeling of the condyle and temporal fossa with destruction of condylar cartilage and subchondral bone leads to postsurgical condylar resorption, with arthralgia and functional limitations. Patients with severe lesions are refractory to conservative treatments, leading to more invasive therapies that range from simple arthrocentesis to open surgery and prosthesis. Although aggressive and with a high risk for the patient, surgical invasive treatments are not always efficient in managing the degenerative lesions. METHODS: We propose a regenerative medicine approach using in-vitro expanded autologous cells from nasal septum applied to the first proof-of-concept patient. After the required quality controls, the cells were injected into each joint by arthrocentesis. Results were monitored by functional assays and image analysis using computed tomography. RESULTS: The cell injection fully reverted the condylar resorption, leading to functional and structural regeneration after 6 months. Computed tomography images showed new cortical bone formation filling the former cavity space, and a partial recovery of condylar and temporal bones. The superposition of the condyle models showed the regeneration of the bone defect, reconstructing the condyle original form. CONCLUSIONS: We propose a new treatment of condylar resorption subsequent to orthognathic surgery, presently treated only by alloplastic total joint replacement. We propose an intra-articular injection of autologous in-vitro expanded cells from the nasal septum. The proof-of-concept treatment of a selected patient that had no alternative therapeutic proposal has given promising results, reaching full regeneration of both the condylar cartilage and bone at 6 months after the therapy, which was fully maintained after 1 year. This first case is being followed by inclusion of new patients with a similar pathological profile to complete an ongoing stage I/II study. TRIAL REGISTRATION: This clinical trial is approved by the National Commission of Ethics in Medical Research (CONEP), Brazil, CAAE 12484813.0.0000.5245, and retrospectively registered in the Brazilian National Clinical Trials Registry and in the USA Clinical Trials Registry under the Universal Trial Number (UTN) U1111-1194-6997 .
Assuntos
Regeneração Óssea , Reabsorção Óssea/cirurgia , Transplante de Células/métodos , Condrócitos/transplante , Cirurgia Ortognática/métodos , Articulação Temporomandibular/cirurgia , Adulto , Reabsorção Óssea/patologia , Células Cultivadas , Humanos , Masculino , Septo Nasal/citologia , Articulação Temporomandibular/fisiologia , Transplante AutólogoRESUMO
In cartilaginous tissues, perichondrium cambium layer may be the source of new cartilage. Human nasal septal perichondrium is considered to be a homogeneous structure in which some authors do not recognize the perichondrium internal zone or the cambium layer as a layer distinct from adjacent cartilage surface. In the present study, we isolated a chondrogenic cell population from human nasal septal cartilage surface zone. Nasoseptal chondrogenic cells were positive for surface markers described for mesenchymal stem cells, with exception of CD146, a perivascular cell marker, which is consistent with their avascular niche in cartilage. Although only Sox-9 was constitutively expressed, they also revealed osteogenic and chondrogenic, but not adipogenic, potentials in vitro, suggesting a more restricted lineage potential compared to mesenchymal stem cells. Interestingly, even in absence of chondrogenic growth factors in the pellet culture system, nasoseptal chondrogenic cells had a capacity to synthesize sulfated glycosaminoglycans, large amounts of collagen type II and to a lesser extent collagen type I. The spontaneous chondrogenic potential of this population of cells indicates that they may be a possible source for cartilage tissue engineering. Besides, the pellet culture system using nasoseptal chondrogenic cells may also be a model for studies of chondrogenesis.
Assuntos
Cartilagem/fisiologia , Separação Celular/métodos , Condrócitos/citologia , Condrogênese , Septo Nasal/citologia , Engenharia Tecidual/métodos , Adipogenia , Adulto , Técnicas de Cultura de Células , Linhagem da Célula , Condrócitos/ultraestrutura , Humanos , Septo Nasal/ultraestrutura , OsteogêneseRESUMO
OBJECTIVE: To compare the reabsorption characteristics of fresh septal cartilage autografts, preserved homografts, and preserved autografts in the nasal dorsum of rabbits. METHODS: Rabbit nasal dorsum cartilage grafts were placed in 3 groups. The first group used fresh autologous cartilage; the second group, alcohol-preserved homologous cartilage; and the third group, alcohol-preserved autologous cartilage. Each rabbit received 2 grafts, one crushed and another noncrushed. After 16 weeks, the grafts were removed for analysis. RESULTS: No graft calcification occurred in any group. Chondrogenesis was observed in all groups. The fresh autograft group had the best results in the evaluation of the area of graft recovered and chondrocyte viability. The preserved autologous and homologous grafts did not differ in relation to any of the variables analyzed. Crushed grafts had inferior results in the area of graft recovered and chondrocyte viability compared with the noncrushed forms. No significant difference among the 3 groups was noted in the thickness of the fibrous capsule that developed around the graft. CONCLUSIONS: The fresh cartilage autograft was superior to the crushed and uncrushed preserved homografts and autografts; both types of preserved grafts had equivalent histological results. The uncrushed forms were superior to the crushed forms.