{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T09:31:43Z","timestamp":1794043903534,"version":"4.8.0"},"reference-count":63,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["Grant ECCS-2025064"],"award-info":[{"award-number":["Grant ECCS-2025064"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Department of Energy, Office of Science, Office of Basic Energy Sciences","doi-asserted-by":"publisher","award":["DE-SC0021173"],"award-info":[{"award-number":["DE-SC0021173"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bone pathologies are becoming increasingly prevalent with an aging population, often necessitating bone grafting procedures. The current gold standard for grafting uses autologous tissue; however, this approach carries limitations such as donor site morbidity. Consequently, there is a growing interest in alternative biomaterials. Polyetheretherketone (PEEK), a thermoplastic with bone-like mechanical properties, has shown promise, although its limited bioactivity remains a critical constraint. Various functionalization strategies have been employed to enhance the biological performance of otherwise inert materials. This study aims to develop a functionalized porous PEEK scaffold to improve bioactivity of the material, thereby promoting human osteoblast (HOB) adhesion, proliferation, and differentiation. PEEK scaffolds were fabricated using fused deposition modeling (FDM) (Apium P155), with a rectilinear pattern alternating at +45\u00b0 and \u221245\u00b0 angles between layers. This configuration generated an interconnected pore network with sizes ranging from \u223c100 to 400 \u03bcm. The scaffolds were further coated with titanium oxide as an additional intervention to enhance bioactivity. Mechanical properties of both porous and solid constructs were evaluated according to ISO 178, a flexural testing standard for plastics. Results indicated that both porous scaffolds exhibited a 10-fold decrease in flexural modulus and were 10 times more flexible compared to the solid counterpart (p &amp;lt; 0.001). The mechanical properties of both porous scaffolds were consistent with values reported for trabecular bone, while the solid construct demonstrated a flexural modulus comparable to cortical bone. These findings suggest that the porous PEEK scaffold, both neat and titanium oxide-coated, possesses mechanical properties similar to bone in vivo, indicating its potential as a mechanically suitable biomaterial for bone grafting applications.<\/jats:p>","DOI":"10.1021\/acsbiomaterials.5c01032","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T01:07:06Z","timestamp":1758676026000},"page":"5838-5849","source":"Crossref","is-referenced-by-count":6,"title":["Fabrication\nand Characterization of a Porous TiO2\u2011Modified PEEK\nScaffold with Enhanced Flexural Compliance\nfor Bone Tissue Engineering"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7969-1201","authenticated-orcid":true,"given":"Martina","family":"Galea Mifsud","sequence":"first","affiliation":[{"name":"King\u2019s College London , , ,","place":["London, U.K., SE1 9RT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Sachan","sequence":"additional","affiliation":[{"name":"University of North Carolina and Carolina State University , , , ,","place":["Raleigh, North Carolina, United\nStates, 27695-7115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J.","family":"Narayan","sequence":"additional","affiliation":[{"name":"University of North Carolina and Carolina State University , , , ,","place":["Raleigh, North Carolina, United\nStates, 27695-7115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Di-Silvio","sequence":"additional","affiliation":[{"name":"King\u2019s College London , , ,","place":["London, U.K., SE1 9RT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Coward","sequence":"additional","affiliation":[{"name":"King\u2019s College London , , ,","place":["London, U.K., SE1 9RT"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"issue":"3","key":"2026081810480624500_cit1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s00590-017-2063-0","article-title":"Treatment\nof Critical-Sized Bone Defects: Clinical and Tissue Engineering Perspectives","volume":"28","author":"Roddy","year":"2018","journal-title":"Eur. 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Orthop Trauma"},{"key":"2026081810480624500_cit4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/9781118886410","volume-title":"Introduction to Tissue Engineering: Applications and Challenges","author":"Birla","year":"2014"},{"issue":"14","key":"2026081810480624500_cit5","doi-asserted-by":"publisher","first-page":"7746","DOI":"10.3390\/ijms25147746","article-title":"Developments\nin Alloplastic Bone Grafts and Barrier Membrane Biomaterials for Periodontal\nGuided Tissue and Bone Regeneration Therapy","volume":"25","author":"Ashfaq","year":"2024","journal-title":"International Journal of Molecular Sciences 2024, Vol. 25, Page 7746"},{"key":"2026081810480624500_cit6","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.biomaterials.2018.09.009","article-title":"Porous\nPEEK Improves\nthe Bone-Implant Interface Compared to Plasma-Sprayed Titanium Coating\non PEEK","volume":"185","author":"Torstrick","year":"2018","journal-title":"Biomaterials"},{"issue":"4","key":"2026081810480624500_cit7","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1002\/jbm.a.31822","article-title":"Effects of Bioactive\nGlass and \u03b2-TCP Containing Three-Dimensional Laser Sintered\nPolyetheretherketone Composites on Osteoblasts in Vitro","volume":"87A","author":"von\nWilmowsky","year":"2008","journal-title":"J. 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Sci."},{"issue":"14","key":"2026081810480624500_cit21","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.3390\/polym13142344","article-title":"Research on\nthe Fused Deposition Modeling of Polyether Ether Ketone","volume":"13","author":"Gao","year":"2021","journal-title":"Polymers 2021, Vol. 13, Page 2344"},{"issue":"8","key":"2026081810480624500_cit22","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.3390\/polym12081665","article-title":"Fused Filament\nFabrication of PEEK: A Review of Process-Structure-Property Relationships","volume":"12","author":"Zanjanijam","year":"2020","journal-title":"Polymers 2020, Vol. 12, Page 1665"},{"issue":"7","key":"2026081810480624500_cit23","doi-asserted-by":"publisher","DOI":"10.1002\/mame.202200668","article-title":"Controlling\nCrystallization: A Key\nFactor during 3D Printing with the Advanced Semicrystalline Polymeric\nMaterials PEEK, PEKK 6002, and PEKK 7002","volume":"308","author":"Rodzen\u0301","year":"2023","journal-title":"Macromol.\nMater. 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Biomater"},{"issue":"1","key":"2026081810480624500_cit30","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1067\/mse.2003.22","article-title":"Stress shielding and bone resorption\nin shoulder arthroplasty","volume":"12","author":"Nagels","year":"2003","journal-title":"Journal of Shoulder\nand Elbow Surgery"},{"issue":"4","key":"2026081810480624500_cit31","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.spinee.2023.10.005","article-title":"An Investigational\nTime Course Study of Titanium Plasma Spray on Osseointegration of\nPEEK and Titanium Implants: An in Vivo Ovine Model","volume":"24","author":"Cunningham","year":"2024","journal-title":"Spine Journal"},{"key":"2026081810480624500_cit32","doi-asserted-by":"publisher","first-page":"e471","DOI":"10.1016\/j.wneu.2022.10.006","article-title":"A Comparison\nof Polyetheretherketone and Titanium-Coated Polyetheretherketone in\nMinimally Invasive Transforaminal Lumbar Interbody Fusion: A Randomized\nClinical Trial","volume":"168","author":"Singhatanadgige","year":"2022","journal-title":"World Neurosurg"},{"key":"2026081810480624500_cit33","doi-asserted-by":"publisher","first-page":"391","DOI":"10.2147\/MDER.S180482","article-title":"Porous Titanium-Coated\nPolyetheretherketone Implants\nExhibit an Improved Bone\u2013Implant Interface: An in Vitro and\nin Vivo Biochemical, Biomechanical, and Histological Study","volume":"11","author":"Cheng","year":"2018","journal-title":"Med. Devices (Auckl"},{"issue":"5","key":"2026081810480624500_cit34","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/j.spinee.2014.12.018","article-title":"Plasma-Sprayed Titanium Coating to Polyetheretherketone\nImproves the Bone-Implant Interface","volume":"15","author":"Walsh","year":"2015","journal-title":"Spine Journal"},{"key":"2026081810480624500_cit35","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.jocn.2015.07.017","article-title":"PEEK-Halo Effect\nin Interbody Fusion","volume":"24","author":"Phan","year":"2016","journal-title":"Journal of Clinical Neuroscience"},{"key":"2026081810480624500_cit63","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.5c06631","article-title":"Process-Driven\nOptimization of FDM\nPorous PEEK Structures for Alloplastic Bone Grafts","author":"Mifsud","year":"2025","journal-title":"ACS Omega"},{"issue":"10","key":"2026081810480624500_cit36","doi-asserted-by":"publisher","first-page":"2801","DOI":"10.1089\/ten.2006.12.2801","article-title":"Fabrication\nand Characterization of Poly\u00ad(Propylene\nFumarate) Scaffolds with Controlled Pore Structures Using 3-Dimensional\nPrinting and Injection Molding","volume":"12","author":"Lee","year":"2006","journal-title":"Tissue Eng."},{"key":"2026081810480624500_cit37","doi-asserted-by":"publisher","first-page":"21636","DOI":"10.1039\/c2jm31165h","article-title":"Effects of\nOffset Values of Solid\nFreeform Fabricated PCL-b-TCP Scaffolds on Mechanical Properties and\nCellular Activities in Bone Tissue Regeneration","volume":"22","author":"Yeo","year":"2012","journal-title":"J. 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Sci."},{"issue":"6","key":"2026081810480624500_cit44","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11837-009-0081-z","article-title":"Atomic\nLayer Deposition of TiO2 Films on Nanoporous Alumina: Medical Applications","volume":"61","author":"Narayan","year":"2009","journal-title":"JOM - The Member Journal of The Minerals, Metals & Materials\nSociety"},{"key":"2026081810480624500_cit45","first-page":"25","volume-title":"Handbook of X-Ray Photoelectron Spectroscopy","author":"Chastain","year":"1992"},{"issue":"1","key":"2026081810480624500_cit46","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1680\/jsuin.17.00002","article-title":"Contact Angles and Wettability: Towards Common and\nAccurate Terminology","volume":"5","author":"Marmur","year":"2017","journal-title":"Surf. 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Biomed Nanotechnol"},{"issue":"1","key":"2026081810480624500_cit50","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1002\/(SICI)1097-4636(199707)36:1&lt;99::AID-JBM12&gt;3.0.CO;2-E","article-title":"Correlation\nbetween Substratum Roughness and Wettability,\nCell Adhesion, and Cell Migration","volume":"36","author":"Lampin","year":"1997","journal-title":"J. Biomed\nMater. Res."},{"issue":"6","key":"2026081810480624500_cit51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/rb\/rbab050","article-title":"The Effect of Macropore Size of Hydroxyapatite\nScaffold on the Osteogenic\nDifferentiation of Bone Mesenchymal Stem Cells under Perfusion Culture","volume":"8","author":"Shi","year":"2021","journal-title":"Regen Biomater"},{"issue":"11","key":"2026081810480624500_cit52","doi-asserted-by":"publisher","first-page":"3547","DOI":"10.1089\/ten.tea.2010.0014","article-title":"Fluid Shear Stress\nPromotes an Endothelial-like Phenotype\nduring the Early Differentiation of Embryonic Stem Cells","volume":"16","author":"Ahsan","year":"2010","journal-title":"Tissue Eng. Part A"},{"key":"2026081810480624500_cit53","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.actbio.2022.07.017","article-title":"Manufacturing\nof Scaffolds with Interconnected Internal Open Porosity and Surface\nRoughness","volume":"156","author":"Calore","year":"2023","journal-title":"Acta Biomater"},{"issue":"1","key":"2026081810480624500_cit54","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1002\/pen.21785","article-title":"Influence of Molecular\nWeight on Rheological, Thermal, and Mechanical Properties of PEEK","volume":"51","author":"Yuan","year":"2011","journal-title":"Polym. Eng. Sci."},{"key":"2026081810480624500_cit55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jmatprotec.2017.04.027","article-title":"Influence of Thermal Processing Conditions\nin 3D Printing on the\nCrystallinity and Mechanical Properties of PEEK Material","volume":"248","author":"Yang","year":"2017","journal-title":"J. Mater. 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