{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:05:05Z","timestamp":1789736705459,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572940"],"award-info":[{"award-number":["82572940"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82604137"],"award-info":[{"award-number":["82604137"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372572"],"award-info":[{"award-number":["82372572"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82502585"],"award-info":[{"award-number":["82502585"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Loss of electrophysiological guidance from endogenous fibrous\u2010channeled electrical conduction critically impairs repair of the injured tendon\u2013bone interface (TBI). Clinical analysis indicates that the inconsistent efficacy of conventional electrostimulation (ES) therapy arises from the limited penetration depth and insufficient focusing capacity of electrical currents in biological tissues. In this study, we developed a tendon\u2013bone comb, termed the gradient microneedle (GMN), to improve spatial precision of electrical\u2010signal delivery through multiple independent channel units and thereby promote targeted TBI regeneration. Ultrasonic acoustic radiation force was used to guide the graded distribution of piezoelectric nanoparticles within the GMN. In vitro, under ultrasonic stimulation (1\u00a0W), the GMN generated a gradient electric field that closely matched the optimal intensity required to direct the biphasic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo studies demonstrated that the GMN increased host bone integration by 101% compared with control systems and promoted functional recovery in rat and porcine TBI injury models. Additionally, GMN\u2010mediated acoustic\u2010electrical stimulation promoted graded regeneration of the complex by triggering Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    influx and subsequently regulating the FoxO and JAK1\u2010STAT3 signaling pathways. Overall, this study presents a GMN that reconstructs physiological bioelectrical gradients and enhances osteointegration, offering a novel gradient ES strategy for regenerating interfacial tissues.\n                  <\/jats:p>","DOI":"10.1002\/adma.75049","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:16:34Z","timestamp":1789733794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasound\u2010Triggered Tendon\u2013Bone Comb With Axially\u00a0Graded Electrical Gradients for Tendon\u2013Bone Interface Integration"],"prefix":"10.1002","author":[{"given":"Xu","family":"He","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University  Chongqing P. R. China"},{"name":"State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University  Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6296-402X","authenticated-orcid":false,"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Key Laboratory For Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University  Chongqing P. R. China"},{"name":"State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University  Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University  Chongqing P. R. China"},{"name":"State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University  Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University  Chongqing P. R. China"},{"name":"State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University  Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University  Chongqing P. R. China"},{"name":"State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University  Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University  Chongqing P. R. China"},{"name":"State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University  Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jindong","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University  Chongqing P. R. China"},{"name":"State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University  Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Key Laboratory For Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6727-4634","authenticated-orcid":false,"given":"Dingqun","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University  Chongqing P. R. China"},{"name":"State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University  Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University  Chongqing P. R. China"},{"name":"State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University  Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.12.043"},{"issue":"12","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1016\/j.stem.2022.11.007","article-title":"A Mineralizing Pool of Gli1\u2010Expressing Progenitors Builds the Tendon Enthesis and Demonstrates Therapeutic Potential","volume":"29","author":"Fang F.","year":"2022","journal-title":"Cell Stem Cell"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4863"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.4c00468"},{"issue":"40","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202501306","article-title":"Piezoelectric Injectable Anti\u2010Adhesive Hydrogel to Promote Endogenous Healing of Tendon Injuries","volume":"37","author":"Luo R.","year":"2025","journal-title":"Advanced Materials"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010025\u201002031\u2010x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201067193\u20107"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.6c04759"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adi1563"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201008292\u20101"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010025\u201001390\u2010z"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42114\u2010026\u201001617\u2010w"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563\u2010025\u201002214\u2010w"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563\u2010018\u20100268\u20101"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010025\u201001477\u20107"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.bioactmat.2024.06.014","article-title":"Exosomes Derived From Tendon Stem\/Progenitor Cells Enhance Tendon\u2010Bone Interface Healing After Rotator Cuff Repair in a Rat Model","volume":"40","author":"He Y.","year":"2024","journal-title":"Bioactive Materials"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201041594\u2010y"},{"issue":"45","key":"e_1_2_10_19_1","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202409400","article-title":"Biodegradable Piezoelectric\u2010Conductive Integrated Hydrogel Scaffold for Repair of Osteochondral Defects","volume":"36","author":"Liu D.","year":"2024","journal-title":"Advanced Materials"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arthro.2022.12.027"},{"issue":"26","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.202300927","article-title":"Integrated Piezoelectric\/Conductive Composite Cryogel Creates Electroactive Microenvironment for Enhanced Bone Regeneration","volume":"12","author":"Zheng T.","year":"2023","journal-title":"Advanced Healthcare Materials"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.4c11890"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2021.07.015"},{"issue":"29","key":"e_1_2_10_24_1","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202001976","article-title":"Piezocatalytic Tumor Therapy by Ultrasound\u2010Triggered and BaTiO3\u2010Mediated Piezoelectricity","volume":"32","author":"Zhu P.","year":"2020","journal-title":"Advanced Materials"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03353732"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312522"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.1c00622"},{"issue":"1","key":"e_1_2_10_28_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2023.e23318","article-title":"Roles of Mechanosensitive Ion Channels in Immune Cells","volume":"10","author":"Xia K.","year":"2024","journal-title":"Heliyon"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u201000279\u2010w"},{"issue":"16","key":"e_1_2_10_30_1","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202413930","article-title":"LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate Osteoarthritis","volume":"12","author":"Guan M.","year":"2025","journal-title":"Advanced Science"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg7380"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0268\u20100033(00)00089\u20109"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042199\u20101"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c08281"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1155"},{"issue":"32","key":"e_1_2_10_36_1","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202500650","article-title":"In Situ Magnetoelectric Generation of miRNA Sponges and Wireless Electric Stimulus by Conductive Granular Scaffolds for Nerve Regeneration","volume":"37","author":"Pan W.\u2010C.","year":"2025","journal-title":"Advanced Materials"},{"key":"e_1_2_10_37_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.biochi.2019.08.005","article-title":"LIPUS Promotes FOXO1 Accumulation by Downregulating miR\u2010182 to Enhance Osteogenic Differentiation in hPDLCs","volume":"165","author":"Chen D.","year":"2019","journal-title":"Biochimie"},{"key":"e_1_2_10_38_1","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1111\/odi.70019","article-title":"LIPUS Protects PDLSCs from Oxidative Damage and Promotes Alveolar Bone Regeneration via FOXO1","volume":"31","author":"Tang L.","year":"2025","journal-title":"Oral Diseases"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1109\/tuffc.2023.3340721"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi6799"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202407358"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adl1102"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.85873"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.10.010"},{"issue":"2","key":"e_1_2_10_45_1","doi-asserted-by":"crossref","DOI":"10.1002\/adfm.202210275","article-title":"Regulation and Reconstruction of Cell Phenotype Gradients Along the Tendon\u2010Bone Interface","volume":"33","author":"Dang G.\u2010P.","year":"2023","journal-title":"Advanced Functional Materials"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adk6610"},{"issue":"1","key":"e_1_2_10_47_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.physio.2015.06.004","article-title":"Efficacy of Transcutaneous Electrical Nerve Stimulation for Rotator Cuff Tendinopathy: A Systematic Review","volume":"102","author":"Desmeules F.","year":"2016","journal-title":"Physiotherapy"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/03635465251411310"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.02.024"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018\u2010023\u201004496\u20109"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018\u2010022\u201003469\u20108"},{"issue":"3","key":"e_1_2_10_52_1","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.fmre.2024.02.002","article-title":"Apigenin Alleviates Osteoporosis by Orchestrating SIRT1\/HIF1\u03b1 Signaling in Mesenchymal Stem Cells","volume":"5","author":"He X.","year":"2025","journal-title":"Fundamental Research"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201049933\u20103"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201057499\u2010x"},{"issue":"31","key":"e_1_2_10_55_1","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202202542","article-title":"Energy\u2010Supporting Enzyme\u2010Mimic Nanoscaffold Facilitates Tendon Regeneration Based on a Mitochondrial Protection and Microenvironment Remodeling Strategy","volume":"9","author":"Wang S.","year":"2022","journal-title":"Advanced Science"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010026\u201068514\u20100"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.75049","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.75049","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.75049","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:16:36Z","timestamp":1789733796000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.75049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":55,"alternative-id":["10.1002\/adma.75049"],"URL":"https:\/\/doi.org\/10.1002\/adma.75049","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]},"assertion":[{"value":"2026-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e75049"}}