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- Preclinical randomized controlled trial of bilateral discectomy versus bilateral discopexy in Black Merino sheep temporomandibular joint: TEMPOJIMS e Phase 1- histologic, imaging and body weight resultsPublication . Ângelo, David Faustino; Morouço, Pedro; Gil, Florêncio Monje; Mónico, Lisete; González-Garcia, Raúl; Sousa, Rita; Neto, Lia; Caldeira, Inês; Smith, Margaret; Smith, Susan; Sanz, David; Santos, Fábio Abade dos; Pinho, Mário; Carrapiço, Belmira; Cavaco, Sandra; Moura, Carla; Alves, Nuno; Salvado, Francisco; Little, ChristopherIntroduction: The role of temporomandibular joint (TMJ) surgery is not well defined due to a lack of quality randomized controlled clinical trials, comparing different TMJ surgical treatments with medical and placebo interventions. The temporomandibular joint interposal study (TEMPOJIMS) is a rigorous preclinical trial divided in 2 phases. In phase 1 the authors investigated the role of the TMJ disc and in phase 2 the authors evaluated 3 different interposal materials. The present work of TEMPOJIMS e phase 1, aims to evaluate histopathologic and imaging changes of bilateral discectomy and discopexy in Black Merino sheep TMJ, using a high-quality trial following the ARRIVE guidelines. Material and methods: This randomized, blinded and controlled preclinical trial was conducted in 9 Black Merino sheep to investigate histopathologic (primary outcome), imaging and body weight (secondary outcomes) changes after bilateral discectomy, discopexy and sham surgery. Results: Significant changes were noticed in discectomy group, both in imaging and histopathologic analyses. Body weight changes were most pronounced in the discectomy group in the first 4 months after surgery with recovery to baseline weight 6 months after surgery. Discopexy induced nonsignificant changes in histopathologic, imaging and body weight analyses. Conclusions: This study reinforces the importance of developing an effective interposal material to substitute the TMJ disc and the need to explore the molecular mechanisms that underlie TMJ cartilage degeneration. The study design proposed in TEMPOJIMS represents an important progress towards future rigorous TMJ investigations.
- A randomized controlled preclinical trial on 3 interposal temporomandibular joint disc implants: TEMPOJIMS—Phase 2Publication . DF, Angelo; Wang, Y.; Morouço, Pedro; Monje, Florencio; Mónico, Lisete; González‐Garcia, Raúl; Moura, Carla; Alves, Nuno; Sanz, David; Gao, Jin; Sousa, Rita; Neto, Lia; Faísca, Pedro; Salvado, Francisco; López Peña, Monica; Permuy, Maria; Munñoz, FernandoThe effort to develop an effective and safe temporomandibular joint (TMJ) disc substitute has been one of the mainstreams of tissue engineering. Biodegradable customized scaffolds could approach safety and effectiveness to regenerate a new autologous disc, rather than using non‐biodegradable materials. However, it is still technically challenging to mimic the biomechanical properties of the native disc with biodegradable polymers. In this study, new 3D tailored TMJ disc implants were developed: (1) Poly(glycerol sebacate) (PGS) scaffold reinforced with electrospun Poly(εcaprolactone) (PCL) fibers on the outer surface (PGS+PCL); (2) PCL and polyethylene glycol diacrylate (PEGDA) (PCL+PEGDA); and (3) PCL. The TMJ im plants were tested in a randomized preclinical trial, conducted in 24 black Merino sheep TMJ, perfoming bilateral interventions. Histologic, imaging, and kinematics analysis was performed. No statistical changes were observed between the PGS +PCL disc and the control group. The PCL+PEGDA and PCL groups were associated with statistical changes in histology (p = 0.004 for articular cartilage mid‐layer; p = 0.019 for structure changes and p = 0.017 for cell shape changes), imaging (p = 0.027 for global appreciation) and dangerous material fragmentation was observed. No biomaterial particles were observed in the multi‐organ analysis in the different groups. The sheep confirmed to be a relevant animal model for TMJ disc surgery and regenerative approaches. The PCL and PCL+PEGDA discs presented a higher risk to increase degenerative changes, due to material fragmentation. None of the tested discs regenerate a new autologous disc, however, PGS+PCL was safe, demonstrated rapid resorption, and was capable to prevent condyle degenerative changes.
- Biological Treatments for Temporomandibular Joint Disc Disorders: Strategies in Tissue EngineeringPublication . Trindade, Daniela; Cordeiro, Rachel; José, Henrique Cardoso; DF, Angelo; Alves, Nuno; Moura, CarlaThe temporomandibular joint (TMJ) is an important structure for the masticatory system and the pathologies associated with it affect a large part of the population and impair people’s lifestyle. It comprises an articular disc, that presents low regeneration capacities and the existing clinical options for repairing it are not effective. This way, it is imperative to achieve a permanent solution to guarantee a good quality of life for people who suffer from these pathologies. Complete knowledge of the unique characteristics of the disc will make it easier to achieve a successful tissue engineering (TE) construct. Thus, the search for an effective, safe and lasting solution has already started, including materials that replace the disc, is currently growing. The search for a solution based on TE approaches, which involve regenerating the disc. The present work revises the TMJ disc characteristics and its associated diseases. The different materials used for a total disc replacement are presented, highlighting the TE area. A special focus on future trends in the field and part of the solution for the TMJ problems described in this review will involve the development of a promising engineered disc approach through the use of decellularized extracellular matrices.
- Effects of bilateral discectomy and bilateral discopexy on black Merino sheep rumination kinematics: TEMPOJIMS – phase 1 – pilot blinded, randomized preclinical studyPublication . Ângelo, David; Gil, Florencio Monje; González-García, Raúl; Mónico, Lisete; Sousa, Rita; Neto, Lia; Caldeira, Inês; Moura, Carla; Francisco, Luís Carlos; Sanz, David; Alves, Nuno; Salvado, Francisco; Morouço, PedroBackground The temporomandibular joint interposal study (TEMPOJIMS) is a rigorous preclinical trial divided in 2 phases. In phase 1 the authors investigated the role of the TMJ disc and in phase 2 the authors evaluated 3 different interposal materials. The present work of TEMPOJIMS - phase 1, investigated the effects of bilateral discectomy and discopexy in sheep mastication and rumination. Methods This randomized, blinded and controlled preclinical trial (in line with the ARRIVE guidelines) was conducted in 9 Black Merino sheep to evaluate changes in mastication and rumination after bilateral discectomy and bilateral discopexy, by comparing with a sham surgery control group. The outcomes evaluated were: (1) absolute masticatory time; (2) ruminant time per cycle; (3) ruminant kinematics, and (4) ruminant area. After baseline evaluation and surgical interventions, the outcomes were recorded over 3 successive days, every 30 days, for 6 months. Results The first month after intervention seemed to be the critical period for significant kinematic changes in the discectomy and discopexy groups. However, 6 months after the bilateral interventions, no significant changes were noticed when compared with the control group. Conclusions In this study, bilateral discectomy and discopexy had no significant effect in mastication and ruminatory movement. The introduction of kinematic evaluation presents a new challenge that may contribute to the improvement of future studies on the TMJ domain.
- Finite element analysis of a human temporomandibular joint disc: Preliminary resultsPublication . Gomes, Sara; Ângelo, David; Pascoal-Faria, Paula; Mateus, Artur; Alves, NunoThe temporomandibular joint (TMJ) is an important joint that plays a paramount role during the mandibular movement. TMJ disc is an essential component in the normal TMJ, interposed between the mandibular condyle and temporal fossa with the following functions: it distributes the intra-articular load, stabilizes the joints during translation and decreases the wear of the articular surface. The mechanical behaviour study of this element is therefore essential to provide alternative solutions when its replacement becomes essential. The aim of this study is to present a preliminary three dimensional mechanical model to study the stresses distributions at TMJ disc and to provide an efficient tool as an alternative to experimental preclinical studies. The human mandibular condyle, the TMJ disc and the temporal fossa were considered to build the finite element model; additionally, two types of connections were used between the disc and the bone simulating the retrodiscal tissue and lateral pterygoid muscle: frictionless and bonded. At this stage, the elastic behaviour of materials was taken into account. Results show that the computed von Mises stresses are in accordance with previous studies.