{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:22:35Z","timestamp":1791451355989,"version":"4.3.3"},"reference-count":111,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As the population ages, the incidence and prevalence of musculoskeletal degeneration, such as osteoarthritis, increase. While the currently accepted treatment options provide symptomatic and functional improvement, they do not halt the progression of osteoarthritis. This results in the eventual need for surgery for many patients with advanced osteoarthritis. Due to the seemingly inevitable progression of OA, many clinicians and researchers have shifted their focus to regenerative therapies. Orthobiologics, a specific type of regenerative therapy designed to treat orthopedic conditions, has been gaining traction in recent years due to the utilization of autologous biological substances and synthetic peptides in healing musculoskeletal injuries and degenerative conditions. Orthobiologics can be distinguished into one of four classes: cell-based, biologic fluids-based, matrix-based, molecular-based, and based on their composition. In this review, key examples of each class, mechanism of action, and current clinical data for each agent are examined. Limitations of current orthobiologics involve a lack of standardization in the preparation and administration of each agent, as well as uniformity in assessment endpoints across different clinical studies. Lastly, we will discuss future directions of orthobiologics as a therapy for the treatment of osteoarthritis.<\/jats:p>","DOI":"10.3390\/ijms27114738","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T11:57:44Z","timestamp":1779710264000},"page":"4738","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Current State of Orthobiologics in Treatment of Knee Osteoarthritis\u2014Future Directions"],"prefix":"10.3390","volume":"27","author":[{"given":"Woojin","family":"Lee","sequence":"first","affiliation":[{"name":"Warren Alpert Medical School, Brown University, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing Zhao","family":"Ruan","sequence":"additional","affiliation":[{"name":"Warren Alpert Medical School, Brown University, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8227-1864","authenticated-orcid":false,"given":"Jamal J.","family":"Hasoon","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine, McGovern Medical School, UTHealth, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Kulich","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, USA"},{"name":"Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Deer","sequence":"additional","affiliation":[{"name":"Spine and Nerve Center of the Virginias, West Virginia University, Health Sciences Campus, Charleston, WV 25301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8867-2140","authenticated-orcid":false,"given":"Dawood","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The University of Kansas School of Medicine, Kansas City, KS 66045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7095-9078","authenticated-orcid":false,"given":"Franzes Anne Z.","family":"Liongson","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative Care, and Pain Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7545-1722","authenticated-orcid":false,"given":"Elizabeth","family":"Hatfield","sequence":"additional","affiliation":[{"name":"Department of Oral & Maxillofacial Surgery\/Hospital Dentistry, University of Michigan School of Dentistry, Ann Arbor, MI 48104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maged","family":"Guirguis","sequence":"additional","affiliation":[{"name":"Department of Interventional Pain, Oschner Health System, New Orleans, LA 70115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2464-0187","authenticated-orcid":false,"given":"Alan D.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4250-8745","authenticated-orcid":false,"given":"Zachary L.","family":"McCormick","sequence":"additional","affiliation":[{"name":"University Orthopaedic Center, Salt Lake City, UT 84108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6960-9621","authenticated-orcid":false,"given":"Robert Jason","family":"Yong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6276-9056","authenticated-orcid":false,"given":"Christopher L.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Division of Pain Medicine, Department of Anesthesiology and Critical Care, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, 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