Temporomandibular joint regeneration: proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes, and the first human case report

Abstract

BackgroundUpon 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.MethodsWe 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.ResultsThe 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.ConclusionsWe 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 registrationThis 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.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0806-4) contains supplementary material, which is available to authorized users.

Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis

“…Furthermore, these results were consistent with results previously reported for early TMJOA generated by surgical manipulation of the joint 30,31 , local application of chemicals 32,33 , and genetic modification 34,35 . Unlike rheumatoid arthritis and synovitis, TMJOA has a primarily noninflammatory origin 36,37 . The pathological process in TMJOA is characterized by deterioration and abrasion of the articular cartilage and local thickening and remodeling of the underlying bone 36 .…”

Autologous Stem Cells Transplants in the Treatment of Temporomandibular Joints Disorders: A Systematic Review and Meta-Analysis of Clinical Trials

“…The maximum mouth opening variable that was examined in all qualifying reports [ 55 , 56 , 57 , 75 , 76 ]. Due to a weaker level of evidence (single case), the study by de Souza Tesch et al was not taken into account in this synthesis [ 76 ]. The range of mandibular mobility increased during post-intervention observation.…”

“…All of the studies that were identified in the course of this systematic review showed a reduction of pain and an increase of the MMO due to the intra-articular injections of stem cells [ 55 , 56 , 57 , 75 , 76 ]. The pain level was measured with the VAS scale in three studies [ 55 , 57 , 75 ].…”

“…As shown by the modest results of this review, the injection of autologous stem cells into the cavities of TMJs is not popularly performed. The treatment technique that is used by different researchers differs and it can be assumed that it is at the stage of development [ 55 , 56 , 57 , 75 , 76 ]. In the study by Carbonini et al, the solution that was used for intra-abdominal administration (for the subsequent receive and gain of fat-derived stem cells) was prepared using 250 mL of saline, 20 mL of lidocaine, and 0.5 mL of adrenaline, and afterwards 30mL of adipose cells were acquired.…”

Reabsorción condilar de la articulación temporomandibular tras un procedimiento artroscópico

“…Respecto al manejo, se han sugerido múltiples alternativas 8 : conservadoras como la férula oclusal, o tratamientos que incluyen la cirugía ortognática, a pesar de existir riesgo de recaída 9,10 .…”