{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:13:01Z","timestamp":1790093581160,"version":"4.0.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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:p>\n                    Oxidative stress compromise nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and restrict endogenous repair in intervertebral disc degeneration (IDD). Here, human nucleus pulposus (NP) tissues showed that secreted phosphoprotein 1 (SPP1) expression increased with degeneration severity. Screening of 2,987 traditional Chinese medicine (TCM)-derived compounds, followed by cellular validation, identified coptisine as a candidate that reduced SPP1 expression while increasing NP-associated extracellular matrix components in NPMSCs. However, effective intradiscal delivery requires sustained local exposure within the adverse degenerative microenvironment. We therefore embedded coptisine-loaded poly (lactic-co-glycolic acid) microspheres in phenylboronic acid-modified gelatin methacryloyl to form an ROS-responsive depot (Cop@PLGA-GelMA-PBA). The composite showed sustained, oxidant-accelerated release and good cytocompatibility. Under H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    challenge, it preserved mitochondrial membrane potential and SOD2 abundance, while maintaining NP-associated extracellular matrix expression. Notably, SPP1 overexpression weakened these effects. When administered immediately after disc puncture, Cop@PLGA-GelMA-PBA maintained disc height and MRI signal, preserved tissue architecture and attenuated early degeneration. Collectively, these findings support responsive biomaterial delivery of a TCM-derived small molecule as a potential strategy for IDD.\n                  <\/jats:p>","DOI":"10.3389\/fbioe.2026.1945988","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:44:40Z","timestamp":1790091880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ROS-responsive biomaterial delivery of the TCM-derived small molecule coptisine protects stem cells and attenuates intervertebral disc degeneration"],"prefix":"10.3389","volume":"14","author":[{"given":"Shouyun","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]},{"name":"Department of Orthopaedics, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University","place":["Nanjing, Jiangsu Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninghang","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiduo","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Shanghai Sixth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41413-021-00179-5","article-title":"Kindlin-2 inhibits Nlrp3 inflammasome activation in nucleus pulposus to maintain homeostasis of the intervertebral disc","volume":"10","author":"Chen","year":"2022","journal-title":"Bone Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1016\/S0140-6736(20)32340-0","article-title":"Global estimates of the need for rehabilitation based on the global burden of disease study 2019: a systematic analysis for the global burden of disease study 2019","volume":"396","author":"Cieza","year":"2020","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. 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