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The treatment is based on analgesics, non-steroidal anti-inflammatory, corticosteroids, anticonvulsants, or arthrocentesis associated with hyaluronic acid-based viscosupplementation. However, the use of hyaluronic acid alone in viscosupplementation does not seem to be enough to regulate the intra-articular inflammatory process. So, we propose to develop and evaluate the physicochemical and biological properties in vitro of hyaluronic acid hydrogels (HA) associated with ketoprofen (KET) as a new therapeutic treatment for TMD. The hydrogels were synthesized with 3% HA and 0.125, 0.250, 0.500, or 1% KET. Physicochemical analyses of Attenuated Total reflectance-Fourier transform infrared spectroscopy (FTIR), Thermogravimetry (TGA), Rheology by Frequency, Amplitude sweeps, temperature ramp, and scanning electron microscopy (SEM) were performed with or without sterilization and cycled. Cytocompatibility and genotoxicity (micronucleus assay) were performed in mouse macrophages (RAW 264-7) for 24 h. Results: FTIR spectrum showed characteristic absorptions of HA and KET. In the TGA, two mass loss peaks were observed, the first representing the water evaporation at 30 and 100 \u00b0C, and the second peaks between 200 and 300 \u00b0C, indicating the degradation of HA and KET. Rheology tests in the oscillatory regime classified the hydrogels as non-Newtonian fluids, time-dependent, and thixotropic. Mouse macrophages (RAW 264-7) presented viability of 83.6% for HA, 50.7% for KET, and 92.4%, 66.1%, 65.3%, and 87.7% for hydrogels, in addition to the absence of genotoxicity. Conclusions: Hyaluronic acid associated with ketoprofen shows satisfactory physicochemical and biological properties for use as viscosupplementation. As a limiting point of this study, further research is needed to evaluate the pharmacodynamic, toxicological, and pharmacokinetic characteristics of a complete organism<\/jats:p>","DOI":"10.3390\/gels10120811","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T11:17:20Z","timestamp":1733829440000},"page":"811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ketoprofen Associated with Hyaluronic Acid Hydrogel for Temporomandibular Disorder Treatment: An In Vitro Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3804-7632","authenticated-orcid":false,"given":"Diego Garcia","family":"Miranda","sequence":"first","affiliation":[{"name":"Multimaterials and Interfaces Laboratory (LMI), CNRS UMR 5615, University Claude Bernard Lyon 1, University of Lyon, 6 rue Victor Grignard, 69622 Villeurbanne, France"},{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University, Avenida Francisco Jos\u00e9 Longo 777, S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"},{"name":"Laboratory \u201cHealth Systemic Process\u201d (P2S), UR4129, Faculty of Medicine Laennec, University Claude Bernard Lyon 1, University of Lyon, 7 rue Guillaume Paradin, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2682-2796","authenticated-orcid":false,"given":"Lucas de Paula","family":"Ramos","sequence":"additional","affiliation":[{"name":"Laboratory \u201cHealth Systemic Process\u201d (P2S), UR4129, Faculty of Medicine Laennec, University Claude Bernard Lyon 1, University of Lyon, 7 rue Guillaume Paradin, 69008 Lyon, France"},{"name":"School of Dentistry, Federal University of Alfenas\u2014UNIFAL. R. Gabriel Monteiro da Silva, 700\u2014Centro, Alfenas 37130-001, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole Fernanda dos Santos","family":"Lopes","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University, Avenida Francisco Jos\u00e9 Longo 777, S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole Van Der Heijde Fernandes","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University, Avenida Francisco Jos\u00e9 Longo 777, S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0572-074X","authenticated-orcid":false,"given":"Cristina Pacheco","family":"Soares","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Compartement Dynamics, Research and Development Institute, Para\u00edba Valley University, Avenida Shishima Hifumi 2911, S\u00e3o Jos\u00e9 dos Campos 12244-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia Pires","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Oral Biology Division, School of Dentistry, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9LU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius de Paula","family":"Morais","sequence":"additional","affiliation":[{"name":"Anton-Paar, Rua Jos\u00e9 de Magalh\u00e3es 646, S\u00e3o Paulo 04026-090, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7780-9797","authenticated-orcid":false,"given":"Thalita","family":"Sani-Taiariol","sequence":"additional","affiliation":[{"name":"National Space Research Institute, Avenida dos astronautas 1758, S\u00e3o Jos\u00e9 dos Campos 12227-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio Ribeiro","family":"Baldan","sequence":"additional","affiliation":[{"name":"National Space Research Institute, Avenida dos astronautas 1758, S\u00e3o Jos\u00e9 dos Campos 12227-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4344-0578","authenticated-orcid":false,"given":"Luana Marotta Reis de","family":"Vasconcellos","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University, Avenida Francisco Jos\u00e9 Longo 777, S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5707-7565","authenticated-orcid":false,"given":"Alexandre Luiz Souto","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University, Avenida Francisco Jos\u00e9 Longo 777, S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-7300","authenticated-orcid":false,"given":"Brigitte","family":"Grosgogeat","sequence":"additional","affiliation":[{"name":"Multimaterials and Interfaces Laboratory (LMI), CNRS UMR 5615, University Claude Bernard Lyon 1, University of Lyon, 6 rue Victor Grignard, 69622 Villeurbanne, France"},{"name":"Dental School, University Claude Bernard Lyon 1, University of Lyon, 7 rue Guillaume Paradin, 69372 Lyon, France"},{"name":"Service d\u2019Odontologie, Hospices Civils de Lyon, 8 Rue de l\u2019Universit\u00e9, 69007 Lyon, 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