Browsing by Author "Alves, Nuno"
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- Bioengineered temporomandibular joint disk implants: study protocol for a two-phase exploratory randomized preclinical pilot trial in 18 black merino sheep (TEMPOJIMS)Publication . Ângelo, David Faustino; Monje, Florencio Gil; García-González, Raúl; Little, Christopher B.; Mónico, Lisete; Pinho, Mário; Santos, Fábio Abade; Carrapiço, Belmira; Gonçalves, Sandra Cavaco; Morouço, Pedro; Alves, Nuno; Moura, Carla; Wang, Yadong; Jeffries, Eric; Gao, Jin; Sousa, Rita; Neto, Lia Lucas; Caldeira, Daniel; Salvado, Francisco"Background: Preclinical trials are essential to test efficacious options to substitute the temporomandibular joint (TMJ) disk. The contemporary absence of an ideal treatment for patients with severe TMJ disorders can be related to difficulties concerning the appropriate study design to conduct preclinical trials in the TMJ field. These difficulties can be associated with the use of heterogeneous animal models, the use of the contralateral TMJ as control, the absence of rigorous randomized controlled preclinical trials with blinded outcomes assessors, and difficulties involving multidisciplinary teams.
- Biological treatments for temporomandibular joint disc disorders: strategies in tissue engineeringPublication . Trindade, Daniela; Cordeiro, Rachel; Cardoso, Henrique José; DF, Angelo; Alves, Nuno; Moura, CarlaThe temporomandibular joint (TMJ) is an important structure for the masticatory systemand the pathologies associated with it affect a large part of the population and impair people’slifestyle. It comprises an articular disc, that presents low regeneration capacities and the existingclinical options for repairing it are not effective. This way, it is imperative to achieve a permanentsolution to guarantee a good quality of life for people who suffer from these pathologies. Completeknowledge of the unique characteristics of the disc will make it easier to achieve a successful tissueengineering (TE) construct. Thus, the search for an effective, safe and lasting solution has alreadystarted, including materials that replace the disc, is currently growing. The search for a solutionbased on TE approaches, which involve regenerating the disc. The present work revises the TMJ disccharacteristics and its associated diseases. The different materials used for a total disc replacementare presented, highlighting the TE area. A special focus on future trends in the field and part of thesolution for the TMJ problems described in this review will involve the development of a promisingengineered 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 Faustino; 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.
- Evaluation of root canal filling with a bioceramic sealer using micro-computed tomography: a pilot studyPublication . Vasconcelos, Isabel; Pereira, Mário Rito; Ginjeira, António; Franco, Margarida C.; Morouço, Pedro; Alves, NunoThis pilot study aims to define a protocol for optimizing the micro-computed tomography (micro-CT) settings to evaluate in the future research the root canal filling in oval shaped canals. Thirty distal canals of mandibular molars were used. After preparation of the canals, the roots were randomly divided into five groups. The canals were filled with two types of sealers (Endosequence BC Sealer or AH Plus) and two types of gutta percha (Protaper Next cones and Endosequence BC cones), using thermal obturation in comparison with a single cone obturation technique. Each specimen was scanned three times using a micro-CT device at a resolution of 30,1 μm. The first scan was done for selecting the specimen according the inclusion criteria, the second one post-instrumentation and the last micro-CT scan after obturation the specimens. For the present study, the images were only evaluated with qualitative criteria and the settings for acquisition, reconstruction and analysis of micro-CT images were tested.
- High instantaneous inhibitory potential of Bictegravir and the new Spiro-β-Lactam BSS-730A for HIV-2 isolates from RAL-Naïve and RAL-Failing patientsPublication . Bártolo, Inês; Moranguinho, Inês; Gonçalves, Paloma; Diniz, Ana Rita; Borrego, Pedro; Martin, Francisco; Figueiredo, Inês; Gomes, Perpétua; Gonçalves, Fátima; Alves, Américo J. S.; Alves, Nuno; Caixas, Umbelina; Pinto, Inês V.; Barahona, Isabel; Melo, Teresa M. V. D. Pinho e; Taveira, NunoIntegrase inhibitors (INIs) are an important class of drugs for treating HIV-2 infection, given the limited number of drugs active against this virus. While the clinical efficacy of raltegravir and dolutegravir is well established, the clinical efficacy of bictegravir for treating HIV-2 infected patients has not been determined. Little information is available regarding the activity of bictegravir against HIV-2 isolates from patients failing raltegravir-based therapy. In this study, we examined the phenotypic and matched genotypic susceptibility of HIV-2 primary isolates from raltegravir-naïve and raltegravir-failing patients to raltegravir, dolutegravir, and bictegravir, and to the new spiro-β-lactam BSS-730A. The instantaneous inhibitory potential (IIP) was calculated to help predict the clinical activity of bictegravir and BSS-730A. Isolates from raltegravir-naïve patients were highly sensitive to all INIs and BSS-730A. Combined integrase mutations E92A and Q148K conferred high-level resistance to raltegravir, and E92Q and T97A conferred resistance to raltegravir and dolutegravir. The antiviral activity of bictegravir and BSS-730A was not affected by these mutations. BSS-730A displayed strong antiviral synergism with raltegravir. Mean IIP values at Cmax were similar for all INIs and were not significantly affected by resistance mutations. IIP values were significantly higher for BSS-730A than for INIs. The high IIP values of bictegravir and BSS-730A for raltegravir-naïve and raltegravir-resistant HIV-2 isolates highlight their potential value for treating HIV-2 infection. Overall, the results are consistent with the high clinical efficacy of raltegravir and dolutegravir for HIV-2 infection and suggest a promising clinical profile for bictegravir and BSS-730A.
- Instigating Maritime Studies via Rapid Prototyping and Robotics: A Case From the Smartboat InitiativePublication . Teodoro, Pedro; Marat-Mendes, R.; Assunção, Mário; Alves, Nuno; Sanguino, Beatriz; Gaspar, Henrique M.A case on rapid prototyping is presented in this work to exemplify the use of learn, make and share activities to promote maritime studies. SMARTBOAT is an initiative from the Escola Superior Náutica Infante D. Henrique, in Portugal, where students are invited to interact with computer-aided design modelling, additive manufacturing and programming. Such initiative is paramount to instigate and promote higher education studies in science, technology, engineering, art, and mathematics (STEAM). The initiative is presented and discussed, with its main steps and schemes. A step forward is later discussed by the ongoing collaboration with the Norwegian University of Science and Technology (NTNU, Norway), which intend to combine the Portuguese case with recent advancements in robotics and digital twin, such as remote operation via internet of things protocols and web-based tools. The work ends with a discussion on the results and future works on autonomous shipping, as well as a call for the development and sharing of similar initiatives.
- Preclinical randomized controlled trial of bilateral discectomy versus bilateral discopexy in black merino sheep temporomandibular joint: TEMPOJIMS – Phase 1- histologic, imaging and body weight resultsPublication . Ângelo, David Faustino; Morouço, Pedro; Gil, Florencio Monje; Mónico, Lisete; González-Gárcia, 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 - 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 . Ângelo, David Faustino; Wang, Yadong; Morouço, Pedro; Monje, Florencio; Mónico, Lisete; González-Garcia, Raúl; Moura, Carla; Alves, Nuno; Sanz, David; Gao, Jin; Sousa, Rita; Neto, Lia; Faísca, Pedro; Salgado, 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 implants 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.