{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:48:21Z","timestamp":1793062101951,"version":"4.5.0"},"reference-count":97,"publisher":"IOP Publishing","issue":"1","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/questions\/alternative-author-rights-policies\/"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/questions\/alternative-author-rights-policies\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"crossref","award":["Grant agreement No. 810111-EpiCrest2Reg"],"award-info":[{"award-number":["Grant agreement No. 810111-EpiCrest2Reg"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"crossref","award":["grant number 310030_175660\/1"],"award-info":[{"award-number":["grant number 310030_175660\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Centre for Applied Biotechnology and Molecular Medicine","award":["grant number 05\/2021"],"award-info":[{"award-number":["grant number 05\/2021"]}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biofabrication"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Intervertebral disc (IVD) degeneration is the primary contributor to low back pain, the leading cause of disability worldwide. Although various triggers have been associated with IVD degeneration, its precise aetiology remains unclear. Consequently, current treatments fail to address the underlying degradative processes. Mechanical loading plays a critical role in IVD homeostasis, and aberrant mechanical stimulation has been identified as a key driver of extracellular matrix degradation in the proteoglycan-rich core of the IVD\u2014the nucleus pulposus (NPs). Elucidating the molecular mechanisms of IVD mechanotransduction could therefore be pivotal in identifying effective drug targets. However, we are lacking easy-to-use, reliable models to study IVD\u2019s mechanobiological mechanisms in human cells. Here, we present the first mechanically active, microscale, human cell-based NP-on-a-Chip (NPoC) model that mimics the native NP microenvironment and enables controlled investigation of mechanically induced degenerative processes. Starting from primary human NP cells, we demonstrate that hypoxic culture (i.e. 2% O\n                    <jats:sub>2<\/jats:sub>\n                    ) results in 3D constructs with gene expression levels of NP markers (\n                    <jats:italic>ACAN, COL2A1, CDH2, OVOS2<\/jats:italic>\n                    ), and matrix composition (collagen type II and glycosaminoglycans) comparable with the native NP tissue. NPoC constructs respond to cyclic compression in an intensity- and duration-dependent manner. Physiological compression (10%) enhances glycosaminoglycan deposition, whereas hyperphysiological compression (30%), especially if prolonged in time (16 h d\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), induces upregulation of inflammatory and catabolic markers (\n                    <jats:italic>PTGS2, MMP13<\/jats:italic>\n                    ), matrix degradation, and increased apoptosis\u2014thus recapitulating clinical hallmarks of NP degeneration. As a proof of concept for the platform\u2019s perspective utility in therapeutic screening, we demonstrate that inhibition of the mechanoresponsive channel TRPV4 with GSK205 restores baseline expression levels of mechanosensitive and catabolic genes. The new NPoC is thus suitable for studying NP mechanobiology and screening mechanotransduction-targeting drugs, and it may facilitate the future discovery of disease modifying therapies for discogenic low back pain.\n                  <\/jats:p>","DOI":"10.1088\/1758-5090\/ae3d85","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T22:53:58Z","timestamp":1769468038000},"page":"015031","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A mechanically active nucleus pulposus-on-a-chip for studying mechanobiology and therapeutic strategies in intervertebral disc disease"],"prefix":"10.1088","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2041-8557","authenticated-orcid":true,"given":"Olga","family":"Krupkova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0963-8365","authenticated-orcid":true,"given":"Bianca","family":"Aterini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2238-8426","authenticated-orcid":true,"given":"Nader","family":"Rahal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5116-4564","authenticated-orcid":false,"given":"Salim","family":"Darwiche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2707-4870","authenticated-orcid":false,"given":"Martin","family":"Ehrbar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3547-1879","authenticated-orcid":true,"given":"Karoliina","family":"Pelttari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6493-0432","authenticated-orcid":true,"given":"Ivan","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Sch\u00e4ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9189-4278","authenticated-orcid":true,"given":"Arne","family":"Mehrkens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5252-789X","authenticated-orcid":false,"given":"Andrea","family":"Barbero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8228-6441","authenticated-orcid":true,"given":"Andrea","family":"Mainardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"bfae3d85bib1","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1016\/S0140-6736(18)30489-6","type":"journal-article","article-title":"Prevention and treatment of low back pain: evidence, challenges, and promising directions","volume":"391","author":"Foster","year":"2018","journal-title":"Lancet"},{"key":"bfae3d85bib2","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2023.1098100","type":"journal-article","article-title":"Global and regional estimates of clinical and economic burden of low back pain in high-income countries: a systematic review and meta-analysis","volume":"11","author":"Fatoye","year":"2023","journal-title":"Front. 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