{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:04:33Z","timestamp":1790661873687,"version":"4.1.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is a degenerative joint disease characterized by progressive degradation of the articular cartilage matrix, pain-related functional impairment, and a paucity of effective disease-modifying therapies. Curculigoside (Cur), a bioactive compound isolated from Curculigo orchioides, possesses anti-inflammatory and tissue-protective properties; however, its direct intra-articular application is hampered by insufficient local retention and limited sustained action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We developed a Zn\n                      <jats:sup>2+<\/jats:sup>\n                      -coordinated pH-responsive hydrogel microsphere delivery system (PGG-Zn@Cur) based on gellan gum (GG) and \u03b3-polyglutamic acid (\u03b3-PGA) to enable localized intra-articular delivery of Cur. Its cytocompatibility and chondroprotective effects were evaluated in IL-1\u03b2-stimulated chondrocytes. Transcriptomic analysis was further performed to investigate the potential molecular mechanisms underlying its therapeutic effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PGG-Zn@Cur exhibited excellent cytocompatibility and restored cartilage matrix metabolic homeostasis in IL-1\u03b2-stimulated chondrocytes, as evidenced by increased COL2A1 and ACAN expression and reduced MMP13, ADAMTS5, and iNOS levels. Transcriptomic analysis implicated PI3K-AKT signaling and apoptosis-related pathways in the chondroprotective effects mediated by PGG-Zn@Cur. Mechanistically, PGG-Zn@Cur suppressed PI3K-AKT pathway hyperactivation, downregulated Cleaved Caspase-3 and Bax expression, attenuated chondrocyte apoptosis, and alleviated cartilage degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings establish PGG-Zn@Cur as a microenvironment-responsive intra-articular platform that maintains cartilage matrix homeostasis and alleviates PI3K-AKT-associated apoptosis-related responses, offering a promising strategy for disease-modifying OA therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbioe.2026.1924086","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:48:09Z","timestamp":1790660889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["pH-responsive Zn2+-coordinated gellan gum\/\u03b3-polyglutamic acid hydrogel microspheres as functional biomaterials for intra-articular delivery: physicochemical design, smart release, and chondroprotective performance in osteoarthritis"],"prefix":"10.3389","volume":"14","author":[{"given":"Kaiming","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Municipal Clinical Research Center for Geriatrics, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Municipal Clinical Research Center for Geriatrics, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Tissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuzheng","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Municipal Clinical Research Center for Geriatrics, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyu","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Municipal Clinical Research Center for Geriatrics, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Municipal Clinical Research Center for Geriatrics, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianding","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Municipal Clinical Research Center for Geriatrics, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"213437","DOI":"10.1016\/j.bioadv.2023.213437","article-title":"Gellan gum-based hydrogels support the recreation of the dermal papilla microenvironment","volume":"150","author":"Abreu","year":"2023","journal-title":"Biomater. 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