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Despite advances in surgical interventions, achieving true biological repair of herniated discs remains a major clinical challenge. This review aims to critically examine the biomechanical landscape of disc herniation, focusing on how altered load transmission, tissue stiffness, and structural disruption influence cellular behavior and tissue regeneration. It further explores mechanobiological mechanisms governing repair and highlights emerging biomimetic models and technologies that integrate mechanical and biological insights to promote functional disc restoration.Methods: A comprehensive literature review was conducted using the Web of Science Core Collection, PubMed (National Library of Medicine), and ScienceDirect databases. The search was limited to peer-reviewed journal articles published in English and focused on studies related to lumbar disc herniation.Results: While decades of research have elucidated the biomechanical factors contributing to disc herniation, recent advances in mechanobiology have uncovered how mechanical cues influence cellular behavior, tissue repair, and degeneration. Evidence suggests that true disc regeneration cannot be achieved through biological replacement or mechanical stabilization alone; rather, it requires restoring functional biomechanics, specifically, the disc\u2019s ability to sense, adapt to, and sustain physiological loading.Conclusion: Viewing disc herniation through a mechanobiological lens offers new opportunities to develop targeted therapies aimed at restoring both tissue integrity and load-bearing functionality, paving the way for more effective regenerative interventions.<\/jats:p>","DOI":"10.14245\/ns.2551668.834","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T01:18:48Z","timestamp":1769735928000},"page":"159-175","update-policy":"https:\/\/doi.org\/10.14245\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Biomechanical Landscape of Lumbar Disc Herniation: Mechanobiological Insights Into Injury and Regeneration"],"prefix":"10.14245","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-1660","authenticated-orcid":true,"given":"Gianluca","family":"Vadala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8566-8952","authenticated-orcid":true,"given":"Fabrizio","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-9325","authenticated-orcid":true,"given":"In-Ho","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9983-3365","authenticated-orcid":true,"given":"Amit","family":"Jain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0696-6530","authenticated-orcid":true,"given":"Javad","family":"Tavakoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"AO Spine Knowledge Forum Degenerative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"5355","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2023.03.024"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xnsj.2024.100328"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-024-08528-8"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2024.110839"},{"key":"ref5","volume-title":"Herniated lumbar disc","author":"Jordan","year":"2009"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.14245\/ns.2550094.047"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bas.2025.105619"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1186\/s12893-025-02992-9"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1186\/s12893-025-02856-2"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9073460"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.inat.2022.101674"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2024.09.007"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14041196"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21144889"},{"key":"ref15","first-page":"357","volume-title":"Mechanisms of failure following simulated repetitive lifting: a clinically relevant biomechanical cadaveric study","author":"Amin","year":"2020"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-016-4416-5"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2015.0086"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23168931"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2025.09.048"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.02.019"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.14245\/ns.2347076.538"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2020.12.062"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1002\/term.1719"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1026"},{"key":"ref25","first-page":"1065","volume-title":"Toward a biochemical understanding of human intervertebral disc degeneration and herniation. 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