{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T04:27:34Z","timestamp":1793939254401,"version":"4.8.0"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of the Mechanical Behavior of Biomedical Materials"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.jmbbm.2026.107648","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:15:14Z","timestamp":1790147714000},"page":"107648","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Gradient orientation governs mechanical and regenerative outcomes in functionally graded bone scaffolds: a coupled finite element\u2013agent-based modelling study"],"prefix":"10.1016","volume":"184","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0504-8364","authenticated-orcid":false,"given":"Ali","family":"Entezari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Badali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg N.","family":"Duda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Checa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.jmbbm.2026.107648_bib1","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1073\/pnas.91.6.2095","article-title":"Molecular analysis of cell surface beta-1, 4-galactosyltransferase function during cell migration","volume":"91","author":"Appeddu","year":"1994","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.jmbbm.2026.107648_bib2","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiomed.2023.107381","article-title":"In silico assessment of the bone regeneration potential of complex porous scaffolds","volume":"165","author":"Asbai-Ghoudan","year":"2023","journal-title":"Comput. Biol. Med."},{"key":"10.1016\/j.jmbbm.2026.107648_bib3","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2023.1261108","article-title":"Computational design and evaluation of the mechanical and electrical behavior of a piezoelectric scaffold: a preclinical study","volume":"11","author":"Badali","year":"2024","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.jmbbm.2026.107648_bib4","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.matpr.2023.05.057","article-title":"Finite element analysis based design of biomimetic functionally graded Ti-6Al-4V alloy scaffolds for human cortical bone applications","volume":"90","author":"Bora","year":"2023","journal-title":"Mater. Today Proc."},{"issue":"10","key":"10.1016\/j.jmbbm.2026.107648_bib5","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.tibtech.2012.07.005","article-title":"Recent advances in bone tissue engineering scaffolds","volume":"30","author":"Bose","year":"2012","journal-title":"Trends Biotechnol."},{"issue":"11","key":"10.1016\/j.jmbbm.2026.107648_bib6","doi-asserted-by":"crossref","DOI":"10.3390\/biomimetics9110690","article-title":"Advances in bioceramics for bone regeneration: a narrative review","volume":"9","author":"Brochu","year":"2024","journal-title":"Biomimetics"},{"issue":"22","key":"10.1016\/j.jmbbm.2026.107648_bib7","doi-asserted-by":"crossref","first-page":"5003","DOI":"10.1016\/j.biomaterials.2011.03.064","article-title":"Microstructure design of biodegradable scaffold and its effect on tissue regeneration","volume":"32","author":"Chen","year":"2011","journal-title":"Biomaterials"},{"key":"10.1016\/j.jmbbm.2026.107648_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiomed.2025.110574","article-title":"An in silico study reveals how architectural and mechanical cues jointly regulate angiogenesis and bone regeneration in 3D printed scaffolds","volume":"195","author":"Dazzi","year":"2025","journal-title":"Comput. Biol. Med."},{"issue":"4","key":"10.1016\/j.jmbbm.2026.107648_bib9","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1093\/rb\/rby013","article-title":"Bone tissue engineering via growth factor delivery: from scaffolds to complex matrices","volume":"5","author":"De Witte","year":"2018","journal-title":"Regen. Biomater."},{"key":"10.1016\/j.jmbbm.2026.107648_bib10","article-title":"Osseointegration of functionally graded Ti6Al4V porous implants: histology of the pore network","volume":"155","author":"Deering","year":"2023","journal-title":"Biomater. Adv."},{"issue":"1","key":"10.1016\/j.jmbbm.2026.107648_bib11","doi-asserted-by":"crossref","DOI":"10.1038\/srep22898","article-title":"Gradients in pore size enhance the osteogenic differentiation of human mesenchymal stromal cells in three-dimensional scaffolds","volume":"6","author":"Di Luca","year":"2016","journal-title":"Sci. Rep."},{"issue":"3","key":"10.1016\/j.jmbbm.2026.107648_bib12","first-page":"62","article-title":"Mechanical design of a novel functionally graded lattice structure for long bone scaffolds","volume":"9","author":"Distefano","year":"2025","journal-title":"Design"},{"issue":"3","key":"10.1016\/j.jmbbm.2026.107648_bib13","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1021\/acsbiomaterials.1c01416","article-title":"Promises of functionally graded material in bone regeneration: current trends, properties, and challenges","volume":"8","author":"Dubey","year":"2022","journal-title":"ACS Biomater. Sci. Eng."},{"issue":"3","key":"10.1016\/j.jmbbm.2026.107648_bib14","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0021-9290(97)00127-9","article-title":"Analysis of inter-fragmentary movement as a function of musculoskeletal loading conditions in sheep","volume":"31","author":"Duda","year":"1997","journal-title":"J. Biomech."},{"key":"10.1016\/j.jmbbm.2026.107648_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.jmbbm.2022.105580","article-title":"Nondeterministic multiobjective optimization of 3D printed ceramic tissue scaffolds","volume":"138","author":"Entezari","year":"2023","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"10.1016\/j.jmbbm.2026.107648_bib16","article-title":"On design for additive manufacturing (DAM) parameter and its effects on biomechanical properties of 3D printed ceramic scaffolds","volume":"23","author":"Entezari","year":"2020","journal-title":"Mater. Today Commun."},{"issue":"1","key":"10.1016\/j.jmbbm.2026.107648_bib17","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.201801353","article-title":"Architectural design of 3D printed scaffolds controls the volume and functionality of newly formed bone","volume":"8","author":"Entezari","year":"2019","journal-title":"Adv. Healthcare Mater."},{"key":"10.1016\/j.jmbbm.2026.107648_bib18","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.actbio.2020.10.012","article-title":"A modular design strategy to integrate mechanotransduction concepts in scaffold-based bone tissue engineering","volume":"118","author":"Entezari","year":"2020","journal-title":"Acta Biomater."},{"key":"10.1016\/j.jmbbm.2026.107648_bib19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.actbio.2024.04.020","article-title":"Unraveling the influence of channel size and shape in 3D printed ceramic scaffolds on osteogenesis","volume":"180","author":"Entezari","year":"2024","journal-title":"Acta Biomater."},{"issue":"1 Suppl. A","key":"10.1016\/j.jmbbm.2026.107648_bib20","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1302\/0301-620X.98B.36350","article-title":"Bone grafts and their substitutes","volume":"98-b","author":"Fillingham","year":"2016","journal-title":"Bone Jt. J."},{"key":"10.1016\/j.jmbbm.2026.107648_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.jmbbm.2022.105275","article-title":"Finite element analysis of the influence of porosity and pore geometry on mechanical properties of orthopaedic scaffolds","volume":"132","author":"Gryko","year":"2022","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"10.1016\/j.jmbbm.2026.107648_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2025.123709","article-title":"Emerging technologies for personalised oro-maxillofacial bone regeneration: design strategies and fabrication techniques","volume":"326","author":"Guo","year":"2026","journal-title":"Biomaterials"},{"key":"10.1016\/j.jmbbm.2026.107648_bib23","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.biomaterials.2018.07.017","article-title":"Bone regeneration strategies: engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives","volume":"180","author":"Ho-Shui-Ling","year":"2018","journal-title":"Biomaterials"},{"issue":"7","key":"10.1016\/j.jmbbm.2026.107648_bib24","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nmat1421","article-title":"Porous scaffold design for tissue engineering","volume":"4","author":"Hollister","year":"2005","journal-title":"Nat. Mater."},{"issue":"12","key":"10.1016\/j.jmbbm.2026.107648_bib25","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1023\/A:1018520914512","article-title":"A biomechanical regulatory model for periprosthetic fibrous-tissue differentiation","volume":"8","author":"Huiskes","year":"1997","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"10.1016\/j.jmbbm.2026.107648_bib26","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.3389\/fbioe.2021.753715","article-title":"A critical review on the design, manufacturing and assessment of the bone scaffold for large bone defects","volume":"9","author":"Huo","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.jmbbm.2026.107648_bib27","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2022.995266","article-title":"PCL strut-like scaffolds appear superior to gyroid in terms of bone regeneration within a long bone large defect: an in silico study","volume":"10","author":"Jaber","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.jmbbm.2026.107648_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiomed.2023.107369","article-title":"Design and manufacturing of biomimetic scaffolds for bone repair inspired by bone trabeculae","volume":"165","author":"Kong","year":"2023","journal-title":"Comput. Biol. Med."},{"issue":"9","key":"10.1016\/j.jmbbm.2026.107648_bib29","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S0021-9290(02)00086-6","article-title":"A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading","volume":"35","author":"Lacroix","year":"2002","journal-title":"J. Biomech."},{"issue":"9","key":"10.1016\/j.jmbbm.2026.107648_bib30","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1016\/j.matt.2022.06.003","article-title":"Scaffolds for bone-tissue engineering","volume":"5","author":"Lee","year":"2022","journal-title":"Matter"},{"key":"10.1016\/j.jmbbm.2026.107648_bib31","first-page":"333","article-title":"Gradient scaffolds in bone-soft tissue interface engineering: structural characteristics, fabrication techniques, and emerging trends","volume":"50","author":"Liu","year":"2025","journal-title":"J. Orthop. Transl."},{"key":"10.1016\/j.jmbbm.2026.107648_bib32","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2024.1444986","article-title":"Optimizing scaffold pore size for tissue engineering: insights across various tissue types","volume":"12","author":"Mukasheva","year":"2024","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.jmbbm.2026.107648_bib33","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.actbio.2022.04.008","article-title":"An in silico model predicts the impact of scaffold design in large bone defect regeneration","volume":"145","author":"Perier-Metz","year":"2022","journal-title":"Acta Biomater."},{"key":"10.1016\/j.jmbbm.2026.107648_bib34","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2020.585799","article-title":"Mechano-biological computer model of scaffold-supported bone regeneration: effect of bone graft and scaffold structure on large bone defect tissue patterning","volume":"8","author":"Perier-Metz","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.jmbbm.2026.107648_bib35","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2022.980727","article-title":"A mechanobiological computer optimization framework to design scaffolds to enhance bone regeneration","volume":"10","author":"Perier-Metz","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"issue":"423","key":"10.1016\/j.jmbbm.2026.107648_bib36","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aam8828","article-title":"Mechanobiologically optimized 3D titanium-mesh scaffolds enhance bone regeneration in critical segmental defects in sheep","volume":"10","author":"Pobloth","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.jmbbm.2026.107648_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.jmbbm.2023.106232","article-title":"Optimal mechanical properties of Hydroxyapatite gradient Voronoi porous scaffolds for bone applications \u2014 a numerical study","volume":"148","author":"Rezapourian","year":"2023","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"10.1016\/j.jmbbm.2026.107648_bib38","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.msec.2017.05.017","article-title":"Scaffolds for Bone Tissue Engineering: state of the art and new perspectives","volume":"78","author":"Roseti","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"issue":"2","key":"10.1016\/j.jmbbm.2026.107648_bib39","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines11020325","article-title":"Scaffold guided bone regeneration for the treatment of large segmental defects in long bones","volume":"11","author":"Schulze","year":"2023","journal-title":"Biomedicines"},{"key":"10.1016\/j.jmbbm.2026.107648_bib40","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/729076","article-title":"Design, materials, and mechanobiology of biodegradable scaffolds for bone tissue engineering","volume":"2015","author":"Velasco","year":"2015","journal-title":"Biomed Res. Int."},{"key":"10.1016\/j.jmbbm.2026.107648_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbiomech.2021.110233","article-title":"A time-dependent mechanobiology-based topology optimization to enhance bone growth in tissue scaffolds","volume":"117","author":"Wu","year":"2021","journal-title":"J. Biomech."},{"key":"10.1016\/j.jmbbm.2026.107648_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijmecsci.2023.108828","article-title":"Machine learning-based design for additive manufacturing in biomedical engineering","volume":"266","author":"Wu","year":"2024","journal-title":"Int. J. Mech. Sci."},{"key":"10.1016\/j.jmbbm.2026.107648_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.cma.2024.116911","article-title":"Dynamic optimisation for graded tissue scaffolds using machine learning techniques","volume":"425","author":"Wu","year":"2024","journal-title":"Comput. Methods Appl. Mech. Eng."},{"key":"10.1016\/j.jmbbm.2026.107648_bib44","article-title":"Design and in vitro evaluation of gradient Schwarz Primitive scaffolds with thin-board integration for bone implants","volume":"177","author":"Xiao","year":"2025","journal-title":"Biomater. Adv."},{"key":"10.1016\/j.jmbbm.2026.107648_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.jmbbm.2020.103673","article-title":"Rationally designed functionally graded porous Ti6Al4V scaffolds with high strength and toughness built via selective laser melting for load-bearing orthopedic applications","volume":"104","author":"Xiong","year":"2020","journal-title":"J. Mech. Behav. Biomed. Mater."},{"issue":"2","key":"10.1016\/j.jmbbm.2026.107648_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.cclet.2023.109197","article-title":"Bone tissue engineering scaffold materials: fundamentals, advances, and challenges","volume":"35","author":"Xu","year":"2024","journal-title":"Chin. Chem. Lett."},{"key":"10.1016\/j.jmbbm.2026.107648_bib47","doi-asserted-by":"crossref","DOI":"10.1016\/j.compstruct.2024.118021","article-title":"Additively-manufactured gradient porous bio-scaffolds: permeability, cytocompatibility and mechanical properties","volume":"336","author":"Xu","year":"2024","journal-title":"Compos. Struct."},{"key":"10.1016\/j.jmbbm.2026.107648_bib48","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2022.1029416","article-title":"An experimental and numerical study of the microstructural and biomechanical properties of human peripheral nerve endoneurium for the design of tissue scaffolds","volume":"10","author":"Yan","year":"2022","journal-title":"Frontiers in Bioengineering and Biotechnology"}],"container-title":["Journal of the Mechanical Behavior of Biomedical Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1751616126003176?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1751616126003176?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T04:07:06Z","timestamp":1793938026000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1751616126003176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":48,"alternative-id":["S1751616126003176"],"URL":"https:\/\/doi.org\/10.1016\/j.jmbbm.2026.107648","relation":{},"ISSN":["1751-6161"],"issn-type":[{"value":"1751-6161","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Gradient orientation governs mechanical and regenerative outcomes in functionally graded bone scaffolds: a coupled finite element\u2013agent-based modelling study","name":"articletitle","label":"Article Title"},{"value":"Journal of the Mechanical Behavior of Biomedical Materials","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jmbbm.2026.107648","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"107648"}}