{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:00:50Z","timestamp":1790240450226,"version":"4.1.0"},"reference-count":28,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"publisher","award":["EDUC4-12792"],"award-info":[{"award-number":["EDUC4-12792"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020490","name":"UC Davis Health","doi-asserted-by":"publisher","award":["L23GF6290"],"award-info":[{"award-number":["L23GF6290"]}],"id":[{"id":"10.13039\/100020490","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health (NIH)","award":["R01 AR079211"],"award-info":[{"award-number":["R01 AR079211"]}]},{"name":"National Institutes of Health (NIH)","award":["T32 AR079099"],"award-info":[{"award-number":["T32 AR079099"]}]},{"name":"Lawrence J. Ellison Endowed Chair of Musculoskeletal Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mechanical cues play a critical role in musculoskeletal homeostasis and disease pathophysiology, where excessive loading induces tissue damage and promotes inflammation. Aging further exacerbates this process, particularly in age-related diseases, such as osteoarthritis (OA). Although both hyper-mechanical loading and aging are known to contribute to chronic inflammation in OA and other age-related diseases, their combined effects remain poorly modeled in vitro. Here, we developed a dynamic 3D culture platform integrating gelatin hydrogels, human bone marrow-derived mesenchymal stromal cell (MSC) spheroids, and a compressive bioreactor to recapitulate joint-like mechanical environments. Gelatin hydrogel-encapsulated MSC spheroids maintained mechanical stability under repeated loading (10\u201320 kPa) while preserving cell viability and spreading. Aged MSC spheroids exhibited metabolic reprogramming toward glycolysis, elevated secretion of pro-inflammatory cytokines (IL-6 and IL-8), and increased PIEZO1 expression. Compressive loading further amplified inflammatory signaling and promoted M1-like macrophage polarization, particularly in aged donor-derived MSCs, modeling key features of inflammaging. Dexamethasone suppressed inflammatory cytokine secretion and promoted M2-like macrophage polarization, whereas tocilizumab modulated immune responses without reducing cytokine production. This platform establishes a donor-specific, mechanobiological model of inflammaging for precision therapeutic screening in osteoarthritis and related diseases.<\/jats:p>","DOI":"10.1021\/acsami.6c14409","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T20:02:38Z","timestamp":1788552158000},"page":"48890-48901","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic Compression Reveals Donor-Age-Associated Inflammaging in Human Mesenchymal Stromal Cell Spheroids"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2245-9029","authenticated-orcid":true,"given":"Thi Thai Thanh","family":"Hoang","sequence":"first","affiliation":[{"name":"UC Davis Health , , , ,","place":["Sacramento, California, United States, 95817"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine H.","family":"Griffin","sequence":"additional","affiliation":[{"name":"UC Davis Health , , , ,","place":["Sacramento, California, United States, 95817"]},{"name":"University of California, Davis , , , ,","place":["Davis, California, United States, 95616"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Mierswa","sequence":"additional","affiliation":[{"name":"UC Davis Health , , , ,","place":["Sacramento, California, United States, 95817"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arda","family":"Acimis","sequence":"additional","affiliation":[{"name":"UC Davis Health , , , ,","place":["Sacramento, California, United States, 95817"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1673-3335","authenticated-orcid":true,"given":"J. Kent","family":"Leach","sequence":"additional","affiliation":[{"name":"UC Davis Health , , , ,","place":["Sacramento, California, United States, 95817"]},{"name":"University of California, Davis , , , ,","place":["Davis, California, United States, 95616"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"issue":"1","key":"2026092321465528500_cit1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41572-025-00594-6","article-title":"Osteoarthritis","volume":"11","author":"Tang","year":"2025","journal-title":"Nat. Rev. Dis. 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Leukocyte Biol."},{"issue":"8","key":"2026092321465528500_cit6","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.joca.2004.03.003","article-title":"Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis","volume":"12","author":"Blom","year":"2004","journal-title":"Osteoarthritis Cartilage"},{"issue":"8","key":"2026092321465528500_cit7","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1007\/s10067-024-07042-y","article-title":"Inflammation as a therapeutic target for osteoarthritis: A literature review of clinical trials","volume":"43","author":"Zhu","year":"2024","journal-title":"Clin. Rheumatol."},{"issue":"1","key":"2026092321465528500_cit8","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1186\/s13287-024-03885-z","article-title":"Translational potential of mesenchymal stem cells in regenerative therapies for human diseases: challenges and opportunities","volume":"15","author":"Zhidu","year":"2024","journal-title":"Stem Cell Res. 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Target Ther."},{"issue":"54","key":"2026092321465528500_cit28","doi-asserted-by":"publisher","first-page":"34053","DOI":"10.1039\/C7RA04137C","article-title":"Oxidized cyclodextrin-functionalized injectable gelatin hydrogels as a new platform for tissue-adhesive hydrophobic drug delivery","volume":"7","author":"Hoang Thi","year":"2017","journal-title":"RSC Advances"}],"container-title":["ACS Applied Materials &amp; Interfaces"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsami.6c14409","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aamick\/article-pdf\/18\/36\/48890\/68392393\/am-2026-14409b.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aamick\/article-pdf\/18\/36\/48890\/68392393\/am-2026-14409b.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:10:04Z","timestamp":1790237404000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aamick\/article\/18\/36\/48890\/5421684\/Dynamic-Compression-Reveals-Donor-Age-Associated"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":28,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,9,4]]},"published-print":{"date-parts":[[2026,9,16]]}},"URL":"https:\/\/doi.org\/10.1021\/acsami.6c14409","relation":{},"ISSN":["1944-8244","1944-8252"],"issn-type":[{"value":"1944-8244","type":"print"},{"value":"1944-8252","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]}}}