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Regenerative medicine offers a promising avenue for improving treatment outcomes, with a range of emerging therapies showing potential to alleviate symptoms and promote joint health. Among these, hyaluronic acid and platelet-rich plasma have been widely used as intra-articular treatments to enhance joint lubrication, reduce inflammation, and provide symptomatic relief. Interleukin-1 receptor antagonist protein, autologous conditioned serum, and autologous protein solution represent the next generation of regenerative therapies, offering more disease-modifying effects by inhibiting key mediators of joint inflammation. More recently, the MSC-derived secretome has emerged as an innovative, cell-free approach that leverages the diverse bioactive factors secreted by MSCs to support tissue repair and modulate inflammation. This review highlights the evidence base behind these non-cellular orthobiologic treatments for stifle joint disease, aiming to inform veterinary practitioners and owners about available options and their efficacy in supporting conventional treatments.<\/jats:p>","DOI":"10.3390\/ani15040589","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T12:16:37Z","timestamp":1739880997000},"page":"589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring the Potential of Non-Cellular Orthobiologic Products in Regenerative Therapies for Stifle Joint Diseases in Companion Animals"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1440-3954","authenticated-orcid":false,"given":"Maria","family":"Guerra-Gomes","sequence":"first","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"BoneLab, Faculdade de Medicina Dent\u00e1ria, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"},{"name":"CECAV\u2014Veterinary and Animal Research Centre UTAD, Universidade de Tr\u00e1s-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Tr\u00e1s-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"LAQV\/REQUIMTE, Faculdade de Medicina Dent\u00e1ria, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9985-4529","authenticated-orcid":false,"given":"Carla","family":"Ferreira-Baptista","sequence":"additional","affiliation":[{"name":"BoneLab, Faculdade de Medicina Dent\u00e1ria, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, Faculdade de Medicina Dent\u00e1ria, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-5675","authenticated-orcid":false,"given":"Joana","family":"Barros","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9842-1759","authenticated-orcid":false,"given":"Sofia","family":"Alves-Pimenta","sequence":"additional","affiliation":[{"name":"CECAV\u2014Veterinary and Animal Research Centre UTAD, Universidade de Tr\u00e1s-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Tr\u00e1s-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-2123","authenticated-orcid":false,"given":"Pedro","family":"Gomes","sequence":"additional","affiliation":[{"name":"BoneLab, Faculdade de Medicina Dent\u00e1ria, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, Faculdade de Medicina Dent\u00e1ria, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4879-8624","authenticated-orcid":false,"given":"Bruno","family":"Cola\u00e7o","sequence":"additional","affiliation":[{"name":"CECAV\u2014Veterinary and Animal Research Centre UTAD, Universidade de Tr\u00e1s-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Tr\u00e1s-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e197","DOI":"10.1002\/vetr.197","article-title":"The Epidemiology of Stifle Joint Disease in an Insured Swedish Dog Population","volume":"189","author":"Engdahl","year":"2021","journal-title":"Vet. 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