{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T21:00:16Z","timestamp":1765486816661,"version":"3.41.2"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"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><jats:bold>Objective:<\/jats:bold> To evaluate the biological function of cervical subtotal discectomy prosthesis (CSDP) implantation in a non-human primate model.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A CSDP was tested for cytocompatibility and osseointegration capacity before implantation in non-human primates. Subsequently, the CSDP was improved based on three-dimensional CT measurements of the non-human primate cervical spine. Eight cynomolgus monkeys were selected for removal of the intervertebral disc and lower endplate of the C5\/6 segment to complete the model construction for CSDP implantation. In 18-month follow-up, physiological indices, radiology, and kinematics were assessed to estimate the biological function of the CSDP in non-human primates, including biosafety, osseointegration, and biomechanics.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Co-cultured with the CSDP constituent titanium alloy (Ti6Al4V-AO), the mouse embryo osteoblast precursor cell MC3T3-E1 obtained extended adhesion, remarkable viability status, and cell proliferation. After implantation in the mouse femur for 28\u00a0days, the surface of Ti6Al4V-AO was covered by a large amount of new cancellous bone, which formed further connections with the femur cortical bone, and no toxicity was detected by blood physiology indices or histopathology. After completing implantation in primate models, no infection or osteolysis was observed, nor was any subsidence or displacement of the CSDP observed in CT scans in the 18-month follow-up. In particular, the interior of the cervical vertebra fixation structure was gradually filled with new trabecular bone, and the CSDP had achieved fixation and bony fusion in the vertebral body at 1\u00a0year post-operation. Meanwhile, no signs of inflammation, spinal cord compression, adjacent segment degeneration, or force line changes were observed in subsequent MRI observations. Moreover, there were no pathological changes of the joint trajectory, joint motion range, stride length, or the stance phase ratio revealed in the kinematics analysis at 3, 6, 12, or 18\u00a0months after CSDP implantation.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> We successfully designed a new cervical subtotal discectomy prosthesis and constructed an excellent non-human primate implantation model for the evaluation of subtotal disc replacement arthroplasty. Furthermore, we demonstrated that CSDP had outstanding safety, osseointegration capacity, and biomechanical stability in a non-human primate model, which might be a new choice in the treatment of cervical disc diseases and potentially change future outcomes of degenerative cervical diseases.<\/jats:p>","DOI":"10.3389\/fbioe.2022.997877","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T06:54:16Z","timestamp":1665644056000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cervical subtotal discectomy prosthesis validated in non-human primate model: A novel artificial cervical disc replacement concept?"],"prefix":"10.3389","volume":"10","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Wo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoran","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhonghai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinpei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengjin","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guodong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhizhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1186\/1556-276X-6-332","article-title":"Fabrication of complete titania nanoporous structures via electrochemical anodization of ti","volume":"6","author":"Ali","year":"2011","journal-title":"Nanoscale Res. Lett."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2779","DOI":"10.1097\/01.brs.0000146460.11591.8a","article-title":"Intervertebral disc arthroplasty","volume":"29","author":"Anderson","year":"2004","journal-title":"Spine (Phila Pa 1976)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1007\/s00586-014-3638-7","article-title":"Radiofrequency sacroplasty (rfs) for the treatment of osteoporotic insufficiency fractures","volume":"24","author":"Andresen","year":"2015","journal-title":"Eur. Spine J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"E332","DOI":"10.1097\/BRS.0000000000001789","article-title":"Biomechanical effects of the geometry of ball-and-socket artificial disc on lumbar spine: a finite element study","volume":"42","author":"Choi","year":"2017","journal-title":"Spine (Phila Pa 1976)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1016\/j.spinee.2021.04.018","article-title":"Metal-on-metal versus metal-on-plastic artificial discs in two-level anterior cervical disc replacement: a meta-analysis with follow-up of 5 years or more","volume":"21","author":"Coban","year":"2021","journal-title":"Spine J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.trsl.2017.06.004","article-title":"The traumatic bone: Trauma-induced heterotopic ossification","volume":"186","author":"Dey","year":"2017","journal-title":"Transl. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1007\/s00586-015-4258-6","article-title":"Cervical spine alignment in disc arthroplasty: should we change our perspective?","volume":"24","author":"Di Martino","year":"2015","journal-title":"Eur. Spine J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neubiorev.2018.12.027","article-title":"Kinematic and kinetic gait analysis to evaluate functional recovery in thoracic spinal cord injured rats","volume":"98","author":"Diogo","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"545708","DOI":"10.3389\/fvets.2021.545708","article-title":"A comparison of two-dimensional and three-dimensional techniques for kinematic analysis of the sagittal motion of sheep hindlimbs during walking on a treadmill","volume":"8","author":"Diogo","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"929935","DOI":"10.1097\/00007632-200205010-00008","article-title":"Artificial intervertebral disc replacement using bioactive three-dimensional fabric: design, development, and preliminary animal study","volume":"27","author":"Kotani","year":"2002","journal-title":"Spine (Phila Pa 1976)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1097\/BRS.0b013e3181f5cb87","article-title":"Comparison of cervical spine biomechanics after fixed- and mobile-core artificial disc replacement: a finite element analysis","volume":"36","author":"Lee","year":"2011","journal-title":"Spine (Phila Pa 1976)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.spinee.2020.10.013","article-title":"Comparison of adverse events between cervical disc arthroplasty and anterior cervical discectomy and fusion: a 10-year follow-up","volume":"21","author":"Loidolt","year":"2021","journal-title":"Spine J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.msec.2017.02.070","article-title":"Advances in ultra high molecular weight polyethylene\/hydroxyapatite composites for biomedical applications: a brief review","volume":"76","author":"Macuvele","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/j.media.2012.09.007","article-title":"Spine detection in ct and mr using iterated marginal space learning","volume":"17","author":"Michael","year":"2013","journal-title":"Med. Image Anal."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.3174\/ajnr.A1152","article-title":"Fracture detection in the cervical spine with multidetector ct: 1-mm versus 3-mm axial images","volume":"29","author":"Phal","year":"2008","journal-title":"AJNR. Am. J. Neuroradiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.jmbbm.2017.11.041","article-title":"Porous architected biomaterial for a tibial-knee implant with minimum bone resorption and bone-implant interface micromotion","volume":"78","author":"Rahimizadeh","year":"2018","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"B18","doi-asserted-by":"publisher","first-page":"E5595","DOI":"10.1073\/pnas.1804735115","article-title":"Nt3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury","volume":"115","author":"Rao","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B19","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.actbio.2019.06.015","article-title":"Tribocorrosion of a cocrmo alloy sliding against articular cartilage and the impact of metal ion release on chondrocytes","volume":"94","author":"Stojanovic","year":"2019","journal-title":"Acta Biomater."},{"key":"B20","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1007\/s00586-012-2594-3","article-title":"Footprint mismatch in total cervical disc arthroplasty","volume":"22","author":"Thaler","year":"2013","journal-title":"Eur. Spine J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1039\/c3cs60150a","article-title":"Electrochemical engineering of hollow nanoarchitectures: pulse\/step anodization (si, al, ti) and their applications","volume":"43","author":"Wang","year":"2014","journal-title":"Chem. Soc. Rev."},{"key":"B22","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/s41467-018-02988-5","article-title":"Inhibition of overactive tgf-beta attenuates progression of heterotopic ossification in mice","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1111\/jmp.12235","article-title":"Influence of walking speed on gait parameters of bipedal locomotion in rhesus monkeys","volume":"45","author":"Wei","year":"2016","journal-title":"J. Med. Primatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"680769","DOI":"10.3389\/fbioe.2021.680769","article-title":"Biomechanical analysis of cervical artificial disc replacement using cervical subtotal discectomy prosthesis","volume":"9","author":"Wo","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/2343404","article-title":"Preclinical evaluation of a novel 3d-printed movable lumbar vertebral complex for replacement: in vivo and biomechanical evaluation of goat model","volume":"2021","author":"Zhang","year":"2021","journal-title":"Biomed. Res. Int."},{"key":"B26","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1111\/jmp.12276","article-title":"Combination of kinematic analyses and diffusion tensor tractrography to evaluate the residual motor functions in spinal cord-hemisected monkeys","volume":"46","author":"Zhao","year":"2017","journal-title":"J. Med. Primatol."}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2022.997877\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T06:54:19Z","timestamp":1665644059000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2022.997877\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,13]]},"references-count":25,"alternative-id":["10.3389\/fbioe.2022.997877"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2022.997877","relation":{},"ISSN":["2296-4185"],"issn-type":[{"type":"electronic","value":"2296-4185"}],"subject":[],"published":{"date-parts":[[2022,10,13]]},"article-number":"997877"}}