{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:31:49Z","timestamp":1777937509769,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016036","name":"Health~Holland","doi-asserted-by":"publisher","award":["40-43100-98-022"],"award-info":[{"award-number":["40-43100-98-022"]}],"id":[{"id":"10.13039\/100016036","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch arthritis society","award":["LLP12 and LLP22"],"award-info":[{"award-number":["LLP12 and LLP22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Back pain affects millions globally and in 40% of the cases is attributed to intervertebral disc degeneration. Oral analgesics are associated with adverse systemic side-effects and insufficient pain relief. Local drug delivery mitigates systemic effects and accomplishes higher local dosing. Clinical efficacy of intradiscally injected celecoxib (CXB)-loaded polyesteramide microspheres (PEAMs) was studied in a randomized prospective double-blinded placebo controlled veterinary study. Client-owned dog patients suffering from back pain were treated with CXB-loaded (n = 20) or unloaded PEAMs (\u201cplacebo\u201d) (n = 10) and evaluated by clinical examination, gait analysis, owners\u2019 questionnaires, and MRI at 6 and 12 weeks follow-up. At 6 and 12 weeks, CXB-treated dogs experienced significantly less pain interference with their daily life activities compared to placebo. The risk ratio for treatment success was 1.90 (95% C.I. 1.24\u20132.91, p = 0.023) at week 6 and 1.95 (95% C.I. 1.10\u20133.45, p = 0.036) at week 12. The beneficial effects of CXB-PEAMs were more pronounced for the subpopulation of male dogs and those with no Modic changes in MRI at inclusion in the study; disc protrusion did not affect the outcome. It remains to be determined whether intradiscal injection of CXB-PEAMs, in addition to analgesic properties, has the ability to halt the degenerative process in the long term or restore the disc.<\/jats:p>","DOI":"10.3390\/pharmaceutics13081178","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:44:32Z","timestamp":1627854272000},"page":"1178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Prospective Evaluation of Local Sustained Release of Celecoxib in Dogs with Low Back Pain"],"prefix":"10.3390","volume":"13","author":[{"given":"Tijn","family":"Wiersema","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8836-097X","authenticated-orcid":false,"given":"Anna","family":"Tellegen","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martijn","family":"Beukers","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marijn","family":"van Stralen","sequence":"additional","affiliation":[{"name":"Image Sciences Institute, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Wouters","sequence":"additional","affiliation":[{"name":"Anicura Dierenziekenhuis Dordrecht, Jan Valsterweg 26, 3315 LG Dordrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandy","family":"van de Vooren","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Woike","sequence":"additional","affiliation":[{"name":"DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Mihov","sequence":"additional","affiliation":[{"name":"DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Thies","sequence":"additional","affiliation":[{"name":"DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1585-3052","authenticated-orcid":false,"given":"Laura","family":"Creemers","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Tryfonidou","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"Meij","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/S0140-6736(17)32154-2","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"390","author":"Vos","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/00007632-200002150-00016","article-title":"Low Back Pain in Relation to Lumbar Disc Degeneration","volume":"25","author":"Luoma","year":"2000","journal-title":"Spine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E430","DOI":"10.1097\/BRS.0b013e3182304dfc","article-title":"Are \u201cPatterns\u201d of Lumbar Disc Degeneration Associated with Low Back Pain? New Insights Based on Skipped Level Disc Pathology","volume":"37","author":"Cheung","year":"2012","journal-title":"Spine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.tvjl.2012.10.024","article-title":"Intervertebral disc degeneration in the dog. Part 1: Anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration","volume":"195","author":"Bergknut","year":"2013","journal-title":"Vet. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/j.1526-4637.2010.01045.x","article-title":"What Is the Source of Chronic Low Back Pain and Does Age Play a Role?","volume":"12","author":"DePalma","year":"2011","journal-title":"Pain Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.pmr.2014.01.006","article-title":"Discogenic Low Back Pain","volume":"25","author":"Simon","year":"2014","journal-title":"Phys. Med. Rehabil. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nrrheum.2013.160","article-title":"Role of cytokines in intervertebral disc degeneration: Pain and disc content","volume":"10","author":"Risbud","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_8","first-page":"13","article-title":"The role of cyclooxygenase-2 and inflammatory cytokines in pain induction of herniated lumbar intervertebral disc","volume":"46","author":"Miyamoto","year":"2000","journal-title":"Kobe J. Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/35068566","article-title":"Interleukin-1b-mediated induction of Cox-2 in the CNS contributes to in ammatory pain Hypersensitivity","volume":"410","author":"Samad","year":"2001","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1097\/01.brs.0000231761.73859.2c","article-title":"What is Intervertebral Disc Degeneration, and What Causes It?","volume":"31","author":"Adams","year":"2006","journal-title":"Spine"},{"key":"ref_11","first-page":"523","article-title":"Inflammatory mediators and signalling pathways controlling intervertebral disc degeneration","volume":"32","author":"Navone","year":"2016","journal-title":"Histol. Histopathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1007\/s00586-008-0758-y","article-title":"Modic changes: A systematic review of the literature","volume":"17","author":"Zhang","year":"2008","journal-title":"Eur. Spine J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00586-013-3142-5","article-title":"Disc size markedly influences concentration profiles of intravenously administered solutes in the intervertebral disc: A computational study on glucosamine as a model solute","volume":"23","author":"Motaghinasab","year":"2014","journal-title":"Eur. Spine J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00590-013-1317-8","article-title":"Antibiotic penetration into rabbit nucleus pulposus with discitis","volume":"24","author":"Zhang","year":"2014","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1001\/jama.2017.4571","article-title":"NSAIDs for Chronic Low Back Pain","volume":"317","author":"Enthoven","year":"2017","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1007\/s00296-011-2263-6","article-title":"A turbulent decade for NSAIDs: Update on current concepts of classification, epidemiology, comparative efficacy, and toxicity","volume":"32","author":"Conaghan","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"114147","DOI":"10.1016\/j.bcp.2020.114147","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective","volume":"180","author":"Bindu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.addr.2020.10.012","article-title":"\u201cOld Drugs, New Tricks\u201d\u2014Local controlled drug release systems for treatment of degenerative joint disease","volume":"160","author":"Tryfonidou","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/(SICI)1099-0518(19990215)37:4<391::AID-POLA3>3.0.CO;2-E","article-title":"Amino Acid-Based Bioanalogous Polymers. Synthesis, and Study of Regular Poly(ester amide)s Based on Bis(\u03b1-amino acid) \u03b1,\u03c9-Alkylene Diesters, and Aliphatic Dicarboxylic Acids","volume":"37","author":"Katsarava","year":"1999","journal-title":"J. Polym. Sci. A Polym. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1021\/bm200043u","article-title":"\u03b1-Amino Acid Containing Degradable Polymers as Functional Biomaterials: Rational Design, Synthetic Pathway, and Biomedical Applications","volume":"12","author":"Sun","year":"2011","journal-title":"Biomacromolecules"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3390\/polym3010065","article-title":"Degradable Poly(ester amide)s for Biomedical Applications","volume":"3","author":"Franco","year":"2010","journal-title":"Polymers"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.preteyeres.2014.04.002","article-title":"The potential of using biodegradable microspheres in retinal diseases and other intraocular pathologies","volume":"42","year":"2014","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jconrel.2016.11.003","article-title":"Celecoxib-loaded PEA microspheres as an auto regulatory drug-delivery system after intra-articular injection","volume":"244","author":"Janssen","year":"2016","journal-title":"J. Control Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/jbm.b.33579","article-title":"Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration","volume":"105","author":"Willems","year":"2017","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.spinee.2018.10.014","article-title":"Safety of intradiscal delivery of triamcinolone acetonide by a poly(esteramide) microsphere platform in a large animal model of intervertebral disc degeneration","volume":"19","author":"Tellegen","year":"2019","journal-title":"Spine J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.jconrel.2018.08.019","article-title":"Intradiscal delivery of celecoxib-loaded microspheres restores intervertebral disc integrity in a preclinical canine model","volume":"286","author":"Tellegen","year":"2018","journal-title":"J. Control Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1002\/term.2483","article-title":"Intradiscal application of a PCLA\u2013PEG\u2013PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What\u2019s in it for humans?","volume":"12","author":"Tellegen","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_28","first-page":"169","article-title":"Canine Degenerative Lumbosacral Stenosis: Prevalence, Impact And Management Strategies","volume":"10","author":"Worth","year":"2019","journal-title":"Vet. Med. Res. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1097\/BRS.0b013e31821e5665","article-title":"The Dog as an Animal Model for Intervertebral Disc Degeneration?","volume":"37","author":"Bergknut","year":"2012","journal-title":"Spine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1109","DOI":"10.1002\/jsp2.1109","article-title":"Canine models of spine disorders","volume":"3","author":"Lee","year":"2020","journal-title":"JOR Spine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.cvsm.2010.05.006","article-title":"Degenerative Lumbosacral Stenosis in Dogs","volume":"40","author":"Meij","year":"2010","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1111\/jvim.12127","article-title":"Systematic Review of Nonsteroidal Anti-Inflammatory Drug-Induced Adverse Effects in Dogs","volume":"27","author":"Steagall","year":"2013","journal-title":"J. Vet. Int. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1023\/B:JMSM.0000011821.46166.1e","article-title":"In vitro enzymatic biodegradation of amino acid based poly(ester amide)s biomaterials","volume":"15","author":"Tsitlanadze","year":"2004","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tellegen, A., Beukers, M., and Rudnik-Jansen, I. (2021). Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13030372"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"893","DOI":"10.2460\/ajvr.72.7.893","article-title":"Evaluation of intervertebral disk degeneration in chondrodystrophic and nonchondrodystrophic dogs by use of Pfirrmann grading of images obtained with low-field magnetic resonance imaging","volume":"72","author":"Bergknut","year":"2011","journal-title":"Am. J. Vet. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lee, N.N., Salzer, E., Bach, F.C., Bonilla, A.F., Cook, J.L., Gazit, Z., Grad, S., Ito, K., Smith, L.J., and Vernengo, A. (2021). A comprehensive tool box for large animal studies of intervertebral disc degeneration. JOR Spine, e1162.","DOI":"10.1002\/jsp2.1162"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1148\/radiology.168.1.3289089","article-title":"Imaging of degenerative disk disease","volume":"168","author":"Modic","year":"1988","journal-title":"Radiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1148\/radiology.166.1.3336678","article-title":"Degenerative disk disease: Assessment of changes in vertebral body marrow with MR imaging","volume":"166","author":"Modic","year":"1988","journal-title":"Radiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1532-950X.2007.00288.x","article-title":"Assessment of Decompressive Surgery in Dogs with Degenerative Lumbosacral Stenosis Using Force Plate Analysis and Questionnaires","volume":"36","author":"Suwankong","year":"2007","journal-title":"Vet. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Tellegen, A.R., Willems, N., Tryfonidou, M.A., and Meij, B.P. (2015). Pedicle screw-rod fixation: A feasible treatment for dogs with severe degenerative lumbosacral stenosis. BMC Vet. Res., 11.","DOI":"10.1186\/s12917-015-0614-3"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/j.1532-950X.2005.00068.x","article-title":"Force Plate Analysis Before and After Dorsal Decompression for Treatment of Degenerative Lumbosacral Stenosis in Dogs","volume":"34","author":"Klaveren","year":"2005","journal-title":"Vet. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"291","DOI":"10.7326\/0003-4819-154-4-201102150-00017","article-title":"CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomized Trials","volume":"154","author":"Schulz","year":"2010","journal-title":"Ann. Int. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.2460\/ajvr.74.12.1467","article-title":"Power of treatment success definitions when the Canine Brief Pain Inventory is used to evaluate carprofen treatment for the control of pain and inflammation in dogs with Osteoarthritis","volume":"74","author":"Brown","year":"2013","journal-title":"Am. J. Vet. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/jvim.12004","article-title":"Comparison of Force Plate Gait Analysis and Owner Assessment of Pain Using the Canine Brief Pain Inventory in Dogs with Osteoarthritis","volume":"27","author":"Brown","year":"2013","journal-title":"J. Vet. Intern. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.2165\/11208240-000000000-00000","article-title":"Celecoxib: A Review of its Use for Symptomatic Relief in the Treatment of Osteoarthritis, Rheumatoid Arthritis and Ankylosing Spondylitis","volume":"71","author":"McCormack","year":"2011","journal-title":"Drugs"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.2460\/ajvr.68.10.1089","article-title":"Accuracy of asymmetry indices of ground reaction forces for diagnosis of hind limb lameness in dogs","volume":"68","author":"Fanchon","year":"2007","journal-title":"Am. J. Vet. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s00256-011-1144-0","article-title":"Correlation between T2 relaxation time and intervertebral disk degeneration","volume":"41","author":"Takashima","year":"2012","journal-title":"Skelet. Radiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1532-950X.2014.12112.x","article-title":"Learning Confounds Algometric Assessment of Mechanical Thresholds in Normal Dogs: Learning Affects Algometry in Normal Dogs","volume":"43","author":"Coleman","year":"2014","journal-title":"Vet. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.vaa.2016.09.004","article-title":"Development and initial validation of a sensory threshold examination protocol (STEP) for phenotyping canine pain syndromes","volume":"44","author":"Chang","year":"2017","journal-title":"Vet. Anaesth. Analg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.jpain.2008.12.001","article-title":"Sex, Gender, and Pain: A Review of Recent Clinical and Experimental Findings","volume":"10","author":"Fillingim","year":"2009","journal-title":"J. Pain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e1888","DOI":"10.1002\/pri.1888","article-title":"The effect of age and gender on acute postoperative pain and function following lumbar spine surgeries","volume":"26","author":"Kanaan","year":"2021","journal-title":"Physiother. Res. Int."},{"key":"ref_52","first-page":"184","article-title":"Gender differences in pain and its relief","volume":"52","author":"Pieretti","year":"2016","journal-title":"Ann. Dell\u2019ist. Sup. Sanita"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1007\/s00586-012-2309-9","article-title":"Is the development of Modic changes associated with clinical symptoms? A 14-month cohort study with MRI","volume":"21","author":"Jensen","year":"2012","journal-title":"Eur. Spine J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1097\/01.brs.0000231436.30262.dd","article-title":"A Gold Standard Evaluation of the \u201cDiscogenic Pain\u201d Diagnosis as Determined by Provocative Discography","volume":"31","author":"Carragee","year":"2006","journal-title":"Spine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.spinee.2012.12.002","article-title":"Role of biomechanics in intervertebral disc degeneration and regenerative therapies: What needs repairing in the disc and what are promising biomaterials for its repair?","volume":"13","author":"Iatridis","year":"2013","journal-title":"Spine J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.spinee.2015.06.051","article-title":"Does provocative discography cause clinically important injury to the lumbar intervertebral disc? A 10-year matched cohort study","volume":"16","author":"Cuellar","year":"2016","journal-title":"Spine J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1097\/BRS.0b013e318166e0a2","article-title":"The Effect of Relative Needle Diameter in Puncture and Sham Injection Animal Models of Degeneration","volume":"33","author":"Elliott","year":"2008","journal-title":"Spine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1097\/BRS.0b013e3182027d42","article-title":"The Effect of Injection Volume on Disc Degeneration in a Rat Tail Model","volume":"36","author":"Mao","year":"2011","journal-title":"Spine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1089\/scd.2015.0158","article-title":"Stem Cell Approaches to Intervertebral Disc Regeneration: Obstacles from the Disc Microenvironment","volume":"24","author":"Wang","year":"2015","journal-title":"Stem Cells Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1177\/0300985817726834","article-title":"The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs","volume":"54","author":"Hansen","year":"2017","journal-title":"Vet. Pathol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/8\/1178\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:37:28Z","timestamp":1760164648000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/8\/1178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,30]]},"references-count":60,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["pharmaceutics13081178"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13081178","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,30]]}}}