{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T19:06:09Z","timestamp":1784055969740,"version":"3.55.0"},"reference-count":56,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"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>Intra-articular hyaluronan injections represent a widely used and generally safe therapeutic approach for knee osteoarthritis (OA). However, the side effects of this treatment remain insufficiently studied. Acute post-injection reactions, particularly those arising from an improper technique resulting in the deposition of the therapeutic agent into joint tissues, are well-documented. In contrast, chronic hyaluronan-induced inflammatory responses have received scant attention in the scientific literature. The aim of this study is to characterize for the first time the morphological patterns of chronic granulomatous inflammation induced by exogenous hyaluronan (e-HA) in osteoarthritic knees, focusing on three distinct tissue reactions: synovitis, adipositis, and osteomyelitis. Using a three-case series approach and morphological analysis, we identified e-HA penetration pathways; described associated foreign body responses in the synovial, adipose, and bone tissues of the joints; and emphasized the clinical relevance of these underreported adverse effects. These observations highlight an understudied phenomenon\u2014an active conflict between e-HA and joint tissues that recognize it as a foreign body. The prevalence, clinical significance, and prognostic implications of this phenomenon require further investigation.<\/jats:p>","DOI":"10.3390\/ijms26168073","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T07:41:45Z","timestamp":1755848505000},"page":"8073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hyaluronan-Related Granulomatous Synovitis, Adipositis, and Osteomyelitis in the Osteoarthritic Knee: A Morphological Case Series of Three Patients"],"prefix":"10.3390","volume":"26","author":[{"given":"Vera","family":"Lyalina","sequence":"first","affiliation":[{"name":"School of Clinical Medicine Storozhakov Internal Diseases Department, Pirogov Russian National Research Medical University, 117513 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulnara","family":"Eshmotova","sequence":"additional","affiliation":[{"name":"St. Alexy Metropolitan of Moscow Central Hospital, 119071 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Karavan","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, Medical Institute, Patrice Lumumba Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Korshunov","sequence":"additional","affiliation":[{"name":"St. Alexy Metropolitan of Moscow Central Hospital, 119071 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Zarov","sequence":"additional","affiliation":[{"name":"St. Alexy Metropolitan of Moscow Central Hospital, 119071 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5894-9524","authenticated-orcid":false,"given":"Anton","family":"Bonartsev","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4097-1552","authenticated-orcid":false,"given":"Natalia","family":"Serejnikova","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-9753","authenticated-orcid":false,"given":"Alexey","family":"Prizov","sequence":"additional","affiliation":[{"name":"Department of Traumatology and Orthopedics, Medical Institute, Patrice Lumumba Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7507-7772","authenticated-orcid":false,"given":"George","family":"Airapetov","sequence":"additional","affiliation":[{"name":"Department of Traumatology and Orthopedics, Medical Institute, Patrice Lumumba Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5611-3990","authenticated-orcid":false,"given":"Alexey","family":"Volkov","sequence":"additional","affiliation":[{"name":"St. Alexy Metropolitan of Moscow Central Hospital, 119071 Moscow, Russia"},{"name":"Department of Pathological Anatomy, Medical Institute, Patrice Lumumba Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Marinho, A., Nunes, C., and Reis, S. 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