{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:22:39Z","timestamp":1784132559531,"version":"3.55.0"},"reference-count":147,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Spinal health depends on the dynamic interplay between mechanical forces, biochemical signaling, and cellular behavior. This review explores how key molecular pathways, including integrin, yeas-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), Piezo, and Wingless\/Integrated (Wnt) with \u03b2-catenin, actively shape the structural and functional integrity of spinal tissues. These signaling mechanisms respond to physical cues and interact with inflammatory mediators such as interleukin-1 beta (IL-1\u03b2), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-\u03b1), driving changes that lead to disc degeneration, vertebral fractures, spinal cord injury, and ligament failure. New research is emerging that shows scaffold designs that can directly harness these pathways. Further, new stem cell-based therapies have been shown to promote disc regeneration through targeted differentiation and paracrine signaling. Interestingly, many novel bone and ligament scaffolds are modulating anti-inflammatory signals to enhance tissue repair and integration, as well as prevent scaffold degradation. Neural scaffolds are also arising. These mimic spinal biomechanics and activate Piezo signaling to guide axonal growth and restore motor function. Scientists have begun combining these biological platforms with brain\u2013computer interface technology to restore movement and sensory feedback in patients with severe spinal damage. Although this technology is not fully clinically ready, this field is advancing rapidly. As implantable technology can now mimic physiological processes, molecular signaling, biomechanical design, and neurotechnology opens new possibilities for restoring spinal function and improving the quality of life for individuals with spinal disorders.<\/jats:p>","DOI":"10.3390\/bioengineering12080886","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T08:40:48Z","timestamp":1755765648000},"page":"886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Current Mechanobiological Pathways and Therapies Driving Spinal Health"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-2895","authenticated-orcid":false,"given":"Rahul","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5707-9009","authenticated-orcid":false,"given":"Kyle","family":"Sporn","sequence":"additional","affiliation":[{"name":"Department of Medicine, Norton College of Medicine, 785 E Adams St., Syracuse, NY 13202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3595-5646","authenticated-orcid":false,"given":"Harlene","family":"Kaur","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Massachusetts T.H. Chan School of Medicine, 55 N Lake Avenue, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4384-2693","authenticated-orcid":false,"given":"Akshay","family":"Khanna","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Medical College, Thomas Jefferson University, 1025 Walnut Street #100, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phani","family":"Paladugu","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Medical College, Thomas Jefferson University, 1025 Walnut Street #100, Philadelphia, PA 19107, USA"},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0120-0939","authenticated-orcid":false,"given":"Nasif","family":"Zaman","sequence":"additional","affiliation":[{"name":"Human-Machine Perception Laboratory, Department of Computer Science, University of Nevada Reno, Reno, 1664 N Virginia St., Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-1269","authenticated-orcid":false,"given":"Alireza","family":"Tavakkoli","sequence":"additional","affiliation":[{"name":"Human-Machine Perception Laboratory, Department of Computer Science, University of Nevada Reno, Reno, 1664 N Virginia St., Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nrm2597","article-title":"Mechanotransduction gone awry","volume":"10","author":"Jaalouk","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1231","DOI":"10.1002\/jsp2.1231","article-title":"Intervertebral disc degeneration and how it leads to low back pain","volume":"6","author":"Diwan","year":"2022","journal-title":"JOR Spine"},{"key":"ref_3","unstructured":"Waxenbaum, J.A., Reddy, V., and Futterman, B. (2025, June 05). Anatomy, Back, Intervertebral Discs, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470583\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1083\/jcb.201609037","article-title":"Integrin-mediated mechanotransduction","volume":"215","author":"Sun","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/nmat5023","article-title":"Fibronectin-bound \u03b15\u03b21 integrins sense load and signal to reinforce adhesion in less than a second","volume":"16","author":"Strohmeyer","year":"2017","journal-title":"Nat. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1476-4598-4-37","article-title":"Activation of focal adhesion kinase enhances the adhesion and invasion of pancreatic cancer cells via extracellular signal-regulated kinase-1\/2 signaling pathway activation","volume":"4","author":"Sawai","year":"2005","journal-title":"Mol. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hayes, A.J., and Melrose, J. (2020). Aggrecan, the Primary Weight-Bearing Cartilage Proteoglycan, Has Context-Dependent, Cell-Directive Properties in Embryonic Development and Neurogenesis: Aggrecan Glycan Side Chain Modifications Convey Interactive Biodiversity. Biomolecules, 10.","DOI":"10.3390\/biom10091244"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S333","DOI":"10.1007\/s00586-013-2855-9","article-title":"Mechanical loading of the intervertebral disc: From the macroscopic to the cellular level","volume":"23","author":"Galbusera","year":"2014","journal-title":"Eur. Spine J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5081","DOI":"10.1074\/jbc.273.9.5081","article-title":"Mechanical stressing of integrin receptors induces enhanced tyrosine phosphorylation of cytoskeletally anchored proteins","volume":"273","author":"Schmidt","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Katoh, K. (2025). Integrin and Its Associated Proteins as a Mediator for Mechano-Signal Transduction. Biomolecules, 15.","DOI":"10.3390\/biom15020166"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.actbio.2017.09.007","article-title":"Three-dimensional nano-architected scaffolds with tunable stiffness for efficient bone tissue growth","volume":"63","author":"Maggi","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s00586-008-0745-3","article-title":"Scaffolding in tissue engineering: General approaches and tissue-specific considerations","volume":"17","author":"Chan","year":"2008","journal-title":"Eur. Spine J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41413-022-00190-4","article-title":"Mechanical regulation of bone remodeling","volume":"10","author":"Wang","year":"2022","journal-title":"Bone Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Park, E.J., Myint, P.K., Ito, A., Appiah, M.G., Darkwah, S., Kawamoto, E., and Shimaoka, M. (2020). Integrin-Ligand Interactions in Inflammation, Cancer, and Metabolic Disease: Insights into the Multifaceted Roles of an Emerging Ligand Irisin. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.588066"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1186\/s12974-021-02364-z","article-title":"Circulating extracellular vesicles activate the pyroptosis pathway in the brain following ventilation-induced lung injury","volume":"18","author":"Chavez","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Raman, N., Imran, S.A.M., Ahmad Amin Noordin, K.B., Zaman, W.S.W.K., and Nordin, F. (2022). Mechanotransduction in Mesenchymal Stem Cells (MSCs) Differentiation: A Review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094580"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"952","DOI":"10.4252\/wjsc.v12.i9.952","article-title":"Mechanotransduction of stem cells for tendon repair","volume":"12","author":"Wang","year":"2020","journal-title":"World J. Stem Cells"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Pattnaik, A., Sanket, A.S., Pradhan, S., Sahoo, R., Das, S., Pany, S., Douglas, T.E.L., Dandela, R., Liu, Q., and Rajadas, J. (2023). Designing of gradient scaffolds and their applications in tissue regeneration. Biomaterials, 296.","DOI":"10.1016\/j.biomaterials.2023.122078"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wu, X.M., Han, W.M., Hou, L.Y., Lin, D.D., Li, J.Y., Lin, S.T., Yang, J.P., Liao, L., and Zeng, X.A. (2024). Glutenin-chitosan 3D porous scaffolds with tunable stiffness and systematized microstructure for cultured meat model. Int. J. Biol. Macromol., 267.","DOI":"10.1016\/j.ijbiomac.2024.131438"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1007\/s11914-020-00605-3","article-title":"Gone Caving: Roles of the Transcriptional Regulators YAP and TAZ in Skeletal Development","volume":"18","author":"Kegelman","year":"2020","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s00018-020-03579-8","article-title":"An overview of signaling pathways regulating YAP\/TAZ activity","volume":"78","author":"Heng","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1007\/s11033-023-08329-0","article-title":"Non-hippo kinases: Indispensable roles in YAP\/TAZ signaling and implications in cancer therapy","volume":"50","author":"Zhu","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/s13287-024-04011-9","article-title":"Emerging role and function of Hippo-YAP\/TAZ signaling pathway in musculoskeletal disorders","volume":"15","author":"Han","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.gene.2006.08.027","article-title":"EP4 receptor regulates collagen type-I, MMP-1, and MMP-3 gene expression in human tendon fibroblasts in response to IL-1 beta treatment","volume":"386","author":"Thampatty","year":"2007","journal-title":"Gene"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/jbmr.3876","article-title":"YAP and TAZ Mediate Osteocyte Perilacunar\/Canalicular Remodeling","volume":"35","author":"Kegelman","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1097\/j.pain.0000000000002356","article-title":"Piezo2 mechanosensitive ion channel is located to sensory neurons and nonneuronal cells in rat peripheral sensory pathway: Implications in pain","volume":"162","author":"Shin","year":"2021","journal-title":"Pain"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1038\/nn.4162","article-title":"Piezo2 is the principal mechanotransduction channel for proprioception","volume":"18","author":"Woo","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Liu, H., Hu, J., Zheng, Q., Feng, X., Zhan, F., Wang, X., Xu, G., and Hua, F. (2022). Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.816149"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111786","DOI":"10.1016\/j.cellsig.2025.111786","article-title":"Mechanical stress overload promotes NF-\u03baB\/NLRP3-mediated osteoarthritis synovitis and fibrosis through Piezo1","volume":"132","author":"Yu","year":"2025","journal-title":"Cell. Signal."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Aragona, M., Mhalhel, K., Pansera, L., Montalbano, G., Guerrera, M.C., Levanti, M., Laur\u00e0, R., Abbate, F., Vega, J.A., and German\u00e0, A. (2024). Localization of Piezo 1 and Piezo 2 in Lateral Line System and Inner Ear of Zebrafish (Danio rerio). Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179204"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jiang, D., Zhao, J., Zheng, J., Zhao, Y., Le, M., Qin, D., Huang, Q., Huang, J., Zhao, Q., and Wang, L. (2024). LOX-mediated ECM mechanical stress induces Piezo1 activation in hypoxic-ischemic brain damage and identification of novel inhibitor of LOX. Redox Biol., 76.","DOI":"10.1016\/j.redox.2024.103346"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Garcia-Castorena, J.M., Riester, R., Gamino-Ornelas, M., Ada, N., Guilak, F., and Danalache, M. (2025). PIEZO1-mediated calcium influx transiently alters nuclear mechanical properties via actin remodeling in chondrocytes. Biochem. Biophys. Res. Commun., 742.","DOI":"10.1016\/j.bbrc.2024.151135"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1038\/ncomms2673","article-title":"A role for Piezo2 in EPAC1-dependent mechanical allodynia","volume":"4","author":"Eijkelkamp","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1038\/s41467-023-38241-x","article-title":"Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis","volume":"14","author":"Obeidat","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kumar, R., Sporn, K., Borole, A., Khanna, A., Gowda, C., Paladugu, P., Ngo, A., Jagadeesan, R., Zaman, N., and Tavakkoli, A. (2025). Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease. Diagnostics, 15.","DOI":"10.20944\/preprints202505.0358.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.neuron.2022.11.015","article-title":"Piezo2 channels expressed by colon-innervating TRPV1-lineage neurons mediate visceral mechanical hypersensitivity","volume":"111","author":"Xie","year":"2023","journal-title":"Neuron"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"eaat9897","DOI":"10.1126\/scitranslmed.aat9897","article-title":"The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice","volume":"10","author":"Murthy","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.2147\/JPR.S490459","article-title":"The Role of Mechanosensitive Piezo Channels in Chronic Pain","volume":"17","author":"Wan","year":"2024","journal-title":"J. Pain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.devcel.2009.06.016","article-title":"Wnt\/beta-catenin signaling: Components, mechanisms, and diseases","volume":"17","author":"MacDonald","year":"2009","journal-title":"Dev. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Devos, H., Zoidakis, J., Roubelakis, M.G., Latosinska, A., and Vlahou, A. (2023). Reviewing the Regulators of COL1A1. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210004"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.spinee.2024.12.003","article-title":"Incidence and risk factors for complications following cervical epidural steroid injections","volume":"25","author":"Wadhwa","year":"2025","journal-title":"Spine J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1002\/art.27599","article-title":"Enhancement of intervertebral disc cell senescence by WNT\/\u03b2-catenin signaling-induced matrix metalloproteinase expression","volume":"62","author":"Hiyama","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41413-024-00342-8","article-title":"Wnt\/\u03b2-catenin signaling components and mechanisms in bone formation, homeostasis, and disease","volume":"12","author":"Hu","year":"2024","journal-title":"Bone Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"592","DOI":"10.2319\/090310-519.1","article-title":"Mechanical loading activates \u03b2-catenin signaling in periodontal ligament cells","volume":"81","author":"Premaraj","year":"2011","journal-title":"Angle Orthod."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tigchelaar, S.S., Wadhwa, H., Mathur, M.B., He, Z., and Tharin, S. (2023). Spinal cord injury: A systematic review and meta-analysis of microRNA alterations. BioRxiv.","DOI":"10.1101\/2023.08.05.551159"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1096\/fj.15-275941","article-title":"Inhibition of Wnt\/\u03b2-catenin pathway promotes regenerative repair of cutaneous and cartilage injury","volume":"29","author":"Bastakoty","year":"2015","journal-title":"FASEB J."},{"key":"ref_48","first-page":"2676","article-title":"Astrocytes in rare neurological conditions: Morphological and functional considerations","volume":"529","author":"Ravi","year":"2021","journal-title":"J. Comp. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mahajan, A., Nengroo, M.A., Datta, D., and Katti, D.S. (2023). Converse modulation of Wnt\/\u03b2-catenin signaling during expansion and differentiation phases of Infrapatellar fat pad-derived MSCs for improved engineering of hyaline cartilage. Biomaterials, 302.","DOI":"10.1016\/j.biomaterials.2023.122296"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41413-022-00226-9","article-title":"Current understanding of osteoarthritis pathogenesis and relevant new approaches","volume":"10","author":"Tong","year":"2022","journal-title":"Bone Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Suryawanshi, A., Tadagavadi, R.K., Swafford, D., and Manicassamy, S. (2016). Modulation of Inflammatory Responses by Wnt\/\u03b2-Catenin Signaling in Dendritic Cells: A Novel Immunotherapy Target for Autoimmunity and Cancer. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00460"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.5966\/sctm.2015-0215","article-title":"Stepwise Differentiation of Mesenchymal Stem Cells Augments Tendon-Like Tissue Formation and Defect Repair In Vivo","volume":"5","author":"Yin","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.2174\/13816128113199990350","article-title":"Stem cell-based tissue engineering approaches for musculoskeletal regeneration","volume":"19","author":"Brown","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sakai, T., and Kumagai, K. (2025). Molecular dissection of tendon development and healing: Insights into tenogenic phenotypes and functions. J. Biol. Chem., 301.","DOI":"10.1016\/j.jbc.2025.108353"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"374676","DOI":"10.1155\/2012\/374676","article-title":"Tissue engineering strategies in ligament regeneration","volume":"2012","author":"Yilgor","year":"2012","journal-title":"Stem Cells Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e70192","DOI":"10.1002\/mco2.70192","article-title":"Tissue Engineering and Regenerative Medicine: Perspectives and Challenges","volume":"6","author":"Hoang","year":"2025","journal-title":"MedComm"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ajalik, R.E., Alenchery, R.G., Cognetti, J.S., Zhang, V.Z., McGrath, J.L., Miller, B.L., and Awad, H.A. (2022). Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.846230"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kishimoto, Y., Ohkawara, B., Sakai, T., Ito, M., Masuda, A., Ishiguro, N., Shukunami, C., Docheva, D., and Ohno, K. (2017). Wnt\/\u03b2-catenin signaling suppresses expressions of Scx, Mkx, and Tnmd in tendon-derived cells. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182051"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ciardulli, M.C., Marino, L., Lovecchio, J., Giordano, E., Forsyth, N.R., Selleri, C., Maffulli, N., and Porta, G.D. (2020). Tendon and Cytokine Marker Expression by Human Bone Marrow Mesenchymal Stem Cells in a Hyaluronate\/Poly-Lactic-Co-Glycolic Acid (PLGA)\/Fibrin Three-Dimensional (3D) Scaffold. Cells, 9.","DOI":"10.3390\/cells9051268"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1093\/rheumatology\/keaa248","article-title":"A roadmap to target interleukin-6 in osteoarthritis","volume":"59","author":"Wiegertjes","year":"2020","journal-title":"Rheumatology"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Tateiwa, D., Yoshikawa, H., and Kaito, T. (2019). Cartilage and Bone Destruction in Arthritis: Pathogenesis and Treatment Strategy: A Literature Review. Cells, 8.","DOI":"10.3390\/cells8080818"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"16975","DOI":"10.1073\/pnas.1315862110","article-title":"STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor","volume":"110","author":"Wang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1759720X241283340","DOI":"10.1177\/1759720X241283340","article-title":"What have we learnt from the inhibition of IL-6 in RA and what are the clinical opportunities for patient outcomes?","volume":"16","author":"Taylor","year":"2024","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1523\/JNEUROSCI.2695-17.2017","article-title":"CD44 Signaling Mediates High Molecular Weight Hyaluronan-Induced Antihyperalgesia","volume":"38","author":"Ferrari","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Choi, H., Yeo, M., Kang, Y., Kim, H.J., Park, S.G., Jang, E., Park, S.H., Kim, E., and Kang, S. (2023). Lactate oxidase\/catalase-displaying nanoparticles efficiently consume lactate in the tumor microenvironment to effectively suppress tumor growth. J. Nanobiotechnol., 21.","DOI":"10.1186\/s12951-022-01762-6"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13045-025-01692-4","article-title":"Nanomaterials-driven in situ vaccination: A novel frontier in tumor immunotherapy","volume":"18","author":"Liu","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Feng, Y., Tang, Q., Wang, B., Yang, Q., Zhang, Y., Lei, L., and Li, S. (2024). Targeting the tumor microenvironment with biomaterials for enhanced immunotherapeutic efficacy. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-03005-2"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ymthe.2024.01.005","article-title":"The landscape of nanoparticle-based siRNA delivery and therapeutic development","volume":"32","author":"Moazzam","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"104","DOI":"10.22203\/eCM.v030a08","article-title":"Disc in flames: Roles of TNF-\u03b1 and IL-1\u03b2 in intervertebral disc degeneration","volume":"30","author":"Johnson","year":"2015","journal-title":"Eur. Cells Mater."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Choi, M.C., Jo, J., Park, J., Kang, H.K., and Park, Y. (2019). NF-\u03baB Signaling Pathways in Osteoarthritic Cartilage Destruction. Cells, 8.","DOI":"10.3390\/cells8070734"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-024-01757-9","article-title":"NF-\u03baB in biology and targeted therapy: New insights and translational implications","volume":"9","author":"Guo","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1093\/rheumatology\/kes363","article-title":"Delphinidin inhibits IL-1\u03b2-induced activation of NF-\u03baB by modulating the phosphorylation of IRAK-1(Ser376) in human articular chondrocytes","volume":"52","author":"Haseeb","year":"2013","journal-title":"Rheumatology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"17","DOI":"10.12998\/wjcc.v11.i1.17","article-title":"Endplate role in the degenerative disc disease: A brief review","volume":"11","author":"Velnar","year":"2023","journal-title":"World J. Clin. Cases"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1136\/ard.2007.072447","article-title":"The efficacy of anti-TNF in rheumatoid arthritis, a comparison between randomised controlled trials and clinical practice","volume":"66","author":"Kievit","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4365","DOI":"10.1172\/JCI126809","article-title":"Potential role of iron in repair of inflammatory demyelinating lesions","volume":"129","author":"Lee","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e73786","DOI":"10.7554\/eLife.73786","article-title":"In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis","volume":"12","author":"Donadieu","year":"2023","journal-title":"eLife"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/978-981-13-0947-2_23","article-title":"Naturally-Derived Biomaterials for Tissue Engineering Applications","volume":"1077","author":"Brovold","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1007\/s11999-011-1857-3","article-title":"The role of growth factors in cartilage repair","volume":"469","author":"Fortier","year":"2011","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Wang, M., Wang, J., Xu, X., Li, E., and Xu, P. (2024). Engineering gene-activated bioprinted scaffolds for enhancing articular cartilage repair. Mater. Today Bio, 29.","DOI":"10.1016\/j.mtbio.2024.101351"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"129917","DOI":"10.52965\/001c.129917","article-title":"Molecular Aspects of Cartilage Microfracturation: Rehabilitation Insights","volume":"17","author":"Kacprzak","year":"2025","journal-title":"Orthop. Rev."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"McClurg, O., Tinson, R., and Troeberg, L. (2021). Targeting Cartilage Degradation in Osteoarthritis. Pharmaceuticals, 14.","DOI":"10.3390\/ph14020126"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Tolstova, T., Dotsenko, E., Luzgina, N., and Rusanov, A. (2024). Preconditioning of Mesenchymal Stem Cells Enhances the Neuroprotective Effects of Their Conditioned Medium in an Alzheimer\u2019s Disease In Vitro Model. Biomedicines, 12.","DOI":"10.3390\/biomedicines12102243"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"623","DOI":"10.4252\/wjsc.v16.i6.623","article-title":"Priming mesenchymal stem cells to develop \u201csuper stem cells\u201d","volume":"16","author":"Haider","year":"2024","journal-title":"World J. Stem Cells"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Yang, H., Yang, H., Wang, Q., Ji, H., Qian, T., Qiao, Y., Shi, J., and Cong, M. (2025). Mesenchymal stem cells and their extracellular vesicles: New therapies for cartilage repair. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1591400"},{"key":"ref_85","first-page":"187","article-title":"Leveraging lower body negative pressure for enhanced outcomes in orthopedic arthroplasty\u2014Insights from NASA\u2019s bone health research","volume":"46","author":"Paladugu","year":"2025","journal-title":"Life Sci. Space Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6482","DOI":"10.1523\/JNEUROSCI.5712-03.2004","article-title":"Cell type-specific interleukin-1beta signaling in the CNS","volume":"24","author":"Srinivasan","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12974-020-1728-5","article-title":"A novel role of NLRP3-generated IL-1\u03b2 in the acute-chronic transition of peripheral lipopolysaccharide-elicited neuroinflammation: Implications for sepsis-associated neurodegeneration","volume":"17","author":"Zhao","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.redox.2015.08.009","article-title":"The dual role of iNOS in cancer","volume":"6","author":"Vannini","year":"2015","journal-title":"Redox Biol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Cota Quintero, J.L., Ramos-Pay\u00e1n, R., Romero-Quintana, J.G., Ayala-Ham, A., Berm\u00fadez, M., and Aguilar-Medina, E.M. (2025). Hydrogel-Based Scaffolds: Advancing Bone Regeneration Through Tissue Engineering. Gels, 11.","DOI":"10.3390\/gels11030175"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.reth.2023.09.007","article-title":"Emerging advances in hydrogel-based therapeutic strategies for tissue regeneration","volume":"24","author":"Li","year":"2023","journal-title":"Regen. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"101019","DOI":"10.1016\/j.gendis.2023.04.039","article-title":"Advances in the application of hydrogel-based scaffolds for tendon repair","volume":"11","author":"Chen","year":"2023","journal-title":"Genes Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e2301358","DOI":"10.1002\/advs.202301358","article-title":"Mesoporous Silica Nanoparticles Mediate SiRNA Delivery for Long-Term Multi-Gene Silencing in Intact Plants","volume":"11","author":"Cai","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2217\/nnm-2022-0023","article-title":"Recent advances in mesoporous silica nanoparticle-based targeted drug-delivery systems for cancer therapy","volume":"17","author":"Li","year":"2022","journal-title":"Nanomedicine"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Khaliq, N.U., Lee, J., Kim, J., Kim, Y., Yu, S., Kim, J., Kim, S., Sung, D., and Kim, H. (2023). Mesoporous Silica Nanoparticles as a Gene Delivery Platform for Cancer Therapy. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15051432"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3924858","DOI":"10.1155\/2016\/3924858","article-title":"Preconditioning of Human Mesenchymal Stem Cells to Enhance Their Regulation of the Immune Response","volume":"2016","author":"Saparov","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s11916-023-01188-1","article-title":"Roles of Chemokines in Intervertebral Disk Degeneration","volume":"28","author":"Xue","year":"2024","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1152\/japplphysiol.01545.2011","article-title":"Mechanical strain applied to human fibroblasts differentially regulates skeletal myoblast differentiation","volume":"113","author":"Hicks","year":"2012","journal-title":"J. Appl. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nri3070","article-title":"Monocyte recruitment during infection and inflammation","volume":"11","author":"Shi","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Bess, S.N., Greening, G.J., Rajaram, N., and Muldoon, T.J. (2022). Macrophage-targeted anti-CCL2 immunotherapy enhances tumor sensitivity to 5-fluorouracil in a Balb\/c-CT26 murine colon carcinoma model measured using diffuse reflectance spectroscopy. BMC Immunol., 23.","DOI":"10.1186\/s12865-022-00493-5"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/scrt492","article-title":"TNF\u03b1 and IL-1\u03b2 influence the differentiation and migration of murine MSCs independently of the NF-\u03baB pathway","volume":"5","author":"Sullivan","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13287-015-0080-7","article-title":"Regulation of the inflammatory profile of stromal cells in human breast cancer: Prominent roles for TNF-\u03b1 and the NF-\u03baB pathway","volume":"6","author":"Katanov","year":"2015","journal-title":"Stem Cell Res Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1186\/s13287-023-03602-2","article-title":"Mesenchymal stem cells overexpressing interleukin-10 prevent allergic airway inflammation","volume":"14","author":"Kuang","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.3727\/096368912X653264","article-title":"Intra-articular delivery of purified mesenchymal stem cells from C57BL\/6 or MRL\/MpJ superhealer mice prevents posttraumatic arthritis","volume":"22","author":"Diekman","year":"2013","journal-title":"Cell Transplant."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3762\/bjnano.16.10","article-title":"Nanocarriers and macrophage interaction: From a potential hurdle to an alternative therapeutic strategy","volume":"16","author":"Sukubo","year":"2025","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1038\/jid.2011.212","article-title":"Pushing back: Wound mechanotransduction in repair and regeneration","volume":"131","author":"Wong","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Wang, L., Zhang, J., Qiu, S., Huang, R., Wang, Y., Wang, Y., Li, M., Ye, Q., Zhang, S., and Qi, Z. (2025). IL-33\/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8. Commun. Biol., 8.","DOI":"10.1038\/s42003-025-08119-3"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Kumar, R., Sporn, K., Paladugu, P., Khanna, A., Gowda, C., Ngo, A., Waisberg, E., Ong, J., Jagadeesan, R., and Tavakkoli, A. (2025). Emerging Diagnostic Approaches for Musculoskeletal Disorders: Advances in Imaging, Biomarkers, and Clinical Assessment. Diagnostics, 15.","DOI":"10.20944\/preprints202505.1597.v1"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Li, Q., Yang, Z., Wang, K., Chen, Z., and Shen, H. (2023). Suppression of microglial Ccl2 reduces neuropathic pain associated with chronic spinal compression. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1191188"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Kumar, R., Sporn, K., Gowda, C., Khanna, A., Prabhakar, P., Paladugu, P., Jagadeesan, R., Clarkson, L., Chandrahasegowda, S., and Kumar, T. (2025). Advancing Spine Connectomics and Neural Integration through Machine Learning and Neuroengineering. Preprints, 2025060518.","DOI":"10.20944\/preprints202506.0518.v1"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrm2125","article-title":"Matrix metalloproteinases and the regulation of tissue remodelling","volume":"8","author":"Ewald","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5353","DOI":"10.1093\/emboj\/16.17.5353","article-title":"TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4","volume":"16","author":"Nakao","year":"1997","journal-title":"EMBO J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1046\/j.1523-1747.2002.01641.x","article-title":"Transforming growth factor-beta signaling through the Smad pathway: Role in extracellular matrix gene expression and regulation","volume":"118","author":"Verrecchia","year":"2002","journal-title":"J. Investig. Dermatol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.tips.2020.06.009","article-title":"Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential","volume":"41","author":"Song","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.jcyt.2017.06.008","article-title":"Establishment of NF-\u03baB sensing and interleukin-4 secreting mesenchymal stromal cells as an \u201con-demand\u201d drug delivery system to modulate inflammation","volume":"19","author":"Lin","year":"2017","journal-title":"Cytotherapy"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00441-016-2563-y","article-title":"Effect of inhibiting MMP13 and ADAMTS5 by intra-articular injection of small interfering RNA in a surgically induced osteoarthritis model of mice","volume":"368","author":"Hoshi","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1089\/ten.teb.2014.0014","article-title":"Anti-inflammatory strategies in cartilage repair","volume":"20","author":"Zhang","year":"2014","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Xie, X., Yue, T., Gu, W., Cheng, W., He, L., Ren, W., Li, F., and Piao, J.G. (2023). Recent Advances in Mesoporous Silica Nanoparticles Delivering siRNA for Cancer Treatment. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15102483"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"7891","DOI":"10.2147\/IJN.S328135","article-title":"Drug Delivery of Natural Products Through Nanocarriers for Effective Breast Cancer Therapy: A Comprehensive Review of Literature","volume":"16","author":"Yap","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jconrel.2013.04.021","article-title":"Topical delivery of anti-TNF\u03b1 siRNA and capsaicin via novel lipid-polymer hybrid nanoparticles efficiently inhibits skin inflammation in vivo","volume":"170","author":"Desai","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1074\/jbc.M116.756601","article-title":"Cytokine-induced MMP13 Expression in Human Chondrocytes Is Dependent on Activating Transcription Factor 3 (ATF3) Regulation","volume":"292","author":"Chan","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Hu, Q., and Ecker, M. (2021). Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041742"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1016\/j.ajpath.2013.02.037","article-title":"Inflammatory cytokines associated with degenerative disc disease control aggrecanase-1 (ADAMTS-4) expression in nucleus pulposus cells through MAPK and NF-\u03baB","volume":"182","author":"Tian","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.2147\/JIR.S415527","article-title":"Amygdalin Delays Cartilage Endplate Degeneration and Improves Intervertebral Disc Degeneration by Inhibiting NF-\u03baB Signaling Pathway and Inflammatory Response","volume":"16","author":"Zeng","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Tabeian, H., Betti, B.F., Dos Santos Cirqueira, C., de Vries, T.J., Lobbezoo, F., Ter Linde, A.V., Zandieh-Doulabi, B., Koenders, M.I., Everts, V., and Bakker, A.D. (2019). IL-1\u03b2 Damages Fibrocartilage and Upregulates MMP-13 Expression in Fibrochondrocytes in the Condyle of the Temporomandibular Joint. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092260"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1089\/ten.teb.2009.0451","article-title":"New challenges for intervertebral disc treatment using regenerative medicine","volume":"16","author":"Masuda","year":"2010","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e063925","DOI":"10.1136\/bmjopen-2022-063925","article-title":"Autologous cultured adipose derived mesenchymal stem cells combined with hyaluronic acid hydrogel in the treatment of discogenic low back pain: A study protocol for a phase II randomised controlled trial","volume":"12","author":"Zhang","year":"2022","journal-title":"BMJ Open"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"R67","DOI":"10.1186\/ar4505","article-title":"Growth differentiation factor 6 and transforming growth factor-beta differentially mediate mesenchymal stem cell differentiation, composition, and micromechanical properties of nucleus pulposus constructs","volume":"16","author":"Clarke","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_128","first-page":"71","article-title":"Mesenchymal stem cells: Potential application in intervertebral disc regeneration","volume":"3","author":"Wei","year":"2014","journal-title":"Transl. Pediatr."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1089\/ten.teb.2021.0145","article-title":"Hypoxia-Conditioned Mesenchymal Stem Cells in Tissue Regeneration Application","volume":"28","author":"Yang","year":"2022","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Nakamura, N., Shi, X., Darabi, R., and Li, Y. (2021). Hypoxia in Cell Reprogramming and the Epigenetic Regulations. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.609984"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Camuzi, D., de Amorim, \u00cd.S.S., Ribeiro Pinto, L.F., Oliveira Trivilin, L., Mencalha, A.L., and Soares Lima, S.C. (2019). Regulation Is in the Air: The Relationship between Hypoxia and Epigenetics in Cancer. Cells, 8.","DOI":"10.3390\/cells8040300"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s41392-024-01852-x","article-title":"Harnessing the potential of hydrogels for advanced therapeutic applications: Current achievements and future directions","volume":"9","author":"Lu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Yang, C., Cai, W., Xiang, P., Liu, Y., Xu, H., Zhang, W., Han, F., Luo, Z., and Liang, T. (2024). Viscoelastic hydrogel combined with dynamic compression promotes osteogenic differentiation of bone marrow mesenchymal stem cells and bone repair in rats. Regen. Biomater., 12.","DOI":"10.1093\/rb\/rbae136"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"25867","DOI":"10.1074\/jbc.M114.566554","article-title":"Proteomic analysis reveals age-related changes in tendon matrix composition, with age- and injury-specific matrix fragmentation","volume":"289","author":"Peffers","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Hade, M.D., Suire, C.N., and Suo, Z. (2021). Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine. Cells, 10.","DOI":"10.3390\/cells10081959"},{"key":"ref_136","first-page":"224","article-title":"Bone grafts and biomaterials substitutes for bone defect repair: A review","volume":"2","author":"Wang","year":"2017","journal-title":"Bioact. Mater."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e2411717","DOI":"10.1001\/jamanetworkopen.2024.11717","article-title":"Implementation Strategies to Promote Short-Course Radiation for Bone Metastases","volume":"7","author":"Gillespie","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/jbmr.4166","article-title":"YAP and TAZ Promote Periosteal Osteoblast Precursor Expansion and Differentiation for Fracture Repair","volume":"36","author":"Kegelman","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.gendis.2014.07.005","article-title":"Bone Morphogenetic Protein (BMP) signaling in development and human diseases","volume":"1","author":"Wang","year":"2014","journal-title":"Genes Dis."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Binaymotlagh, R., Chronopoulou, L., and Palocci, C. (2023). Peptide-Based Hydrogels: Template Materials for Tissue Engineering. J. Funct. Biomater., 14.","DOI":"10.3390\/jfb14040233"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"5196","DOI":"10.1039\/C7TB00744B","article-title":"BBP-Functionalized Biomimetic Nanofibrous Scaffold Can Capture BMP2 and Promote Osteogenic Differentiation","volume":"5","author":"Yao","year":"2017","journal-title":"J. Mater. Chem. B"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Barakat, H., Aljutaily, T., Almujaydil, M.S., Algheshairy, R.M., Alhomaid, R.M., Almutairi, A.S., Alshimali, S.I., and Abdellatif, A.A.H. (2022). Amygdalin: A Review on Its Characteristics, Antioxidant Potential, Gastrointestinal Microbiota Intervention, Anticancer Therapeutic and Mechanisms, Toxicity, and Encapsulation. Biomolecules, 12.","DOI":"10.3390\/biom12101514"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41420-021-00472-6","article-title":"Histone modifications centric-regulation in osteogenic differentiation","volume":"7","author":"Li","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1080\/17434440.2025.2498457","article-title":"The potential power of Neuralink-how brain-machine interfaces can revolutionize medicine","volume":"22","author":"Kumar","year":"2025","journal-title":"Expert Rev. Med. Devices"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e16194","DOI":"10.2196\/16194","article-title":"An Integrated Brain-Machine Interface Platform with Thousands of Channels","volume":"21","author":"Musk","year":"2019","journal-title":"J. Med. Internet Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"110471","DOI":"10.1016\/j.jneumeth.2025.110471","article-title":"Advances in endovascular brain computer interface: Systematic review and future implications","volume":"420","author":"Ognard","year":"2025","journal-title":"J. Neurosci. Methods"},{"key":"ref_147","unstructured":"Neuralink (2025, June 04). Neuralink Raises $650 Million Series E. Available online: https:\/\/neuralink.com\/updates\/neuralink-raises-650m-series-e\/."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/12\/8\/886\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:31:51Z","timestamp":1760034711000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/12\/8\/886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":147,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["bioengineering12080886"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering12080886","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]}}}