{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:18:26Z","timestamp":1793139506613,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>The goal of the present investigation was to find a solution to crucial engineering aspects related to the elaboration of multi-layered tissue-biomimicking composites. 3D printing technology was used to manufacture single-layered and gradient multi-layered 3D porous scaffolds made of poly-lactic acid (PLA). The scaffolds manufacturing process was optimized after adjusting key printing parameters. The scaffolds with 60 \u03bcm side length (square-shaped pores) showed increased stiffness values comparing to the other specimens. A silicone adhesive has been further used to join biomedical titanium plates, and the PLA scaffolds; in addition, titania nanotubes (TNTs were produced on the titanium for improved adhesion. The titanium-PLA scaffold single lap joints were evaluated in micro-tensile testing. The electrochemical processing of the titanium surface resulted in a 248% increase of the ultimate strength in the overlap area for dry specimens and 40% increase for specimens immersed in simulated body fluid. Finally, the biocompatibility of the produced scaffolds was evaluated with primary cell populations obtained after isolation from bone residual tissue. The manufactured scaffolds present promising features for applications in orthopedic implantology and are worth further.<\/jats:p>","DOI":"10.3390\/polym13050682","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T02:36:13Z","timestamp":1614220573000},"page":"682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Gradient 3D Printed PLA Scaffolds on Biomedical Titanium: Mechanical Evaluation and Biocompatibility"],"prefix":"10.3390","volume":"13","author":[{"given":"Diana V.","family":"Portan","sequence":"first","affiliation":[{"name":"Department of Mechanical and Aeronautics Engineering, Laboratory of Biomechanics and Biomedical Engineering, University of Patras, 265 04 Patras, Greece"},{"name":"Department of Mechanical Engineering and Aeronautics, Applied Mechanics &amp; Vibrations Laboratory, University of Patras, 265 04 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Ntoulias","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Aeronautics, Applied Mechanics &amp; Vibrations Laboratory, University of Patras, 265 04 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Mantzouranis","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Aeronautics, Applied Mechanics &amp; Vibrations Laboratory, University of Patras, 265 04 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanassios P.","family":"Fortis","sequence":"additional","affiliation":[{"name":"Panarcadian General Hospital, B\u2019 Orthopedics, 22100 Tripoli, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina D.","family":"Deligianni","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aeronautics Engineering, Laboratory of Biomechanics and Biomedical Engineering, University of Patras, 265 04 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demosthenes","family":"Polyzos","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Aeronautics, Applied Mechanics &amp; Vibrations Laboratory, University of Patras, 265 04 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilis","family":"Kostopoulos","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Aeronautics, Applied Mechanics &amp; Vibrations Laboratory, University of Patras, 265 04 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102977","DOI":"10.1016\/j.arabjc.2020.102977","article-title":"PEEK (Polyether-ether-ketone) and its composite materials in orthopedic implantation","volume":"14","author":"Ma","year":"2021","journal-title":"Arab. J. Chem."},{"key":"ref_2","unstructured":"Kumta, P.N., Yu, G., and Roy, A. (2021). Biomimetic Plywood Motifs for Bone Tissue Engineering. (2021\/0000602 A1), U.S. Patent."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6228","DOI":"10.1016\/j.biomaterials.2009.07.057","article-title":"Development and analysis of multi-layer scaffolds for tissue engineering","volume":"30","author":"Papenburg","year":"2009","journal-title":"Biomaterials"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"117079","DOI":"10.1016\/j.carbpol.2020.117079","article-title":"Tanfloc\/heparin polyelectrolyte multilayers improve osteogenic differentiation of adipose-derived stem cells on titania nanotube surfaces","volume":"251","author":"Sabino","year":"2021","journal-title":"Carbohydrate Polymers"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Taherian, M.H., Rezazadeh, M., and Taji, A. (2021). Optimum Surface Roughness for Titanium Coated PEEK Produced by Electron Beam PVD for Orthopedic Applications. Mater. Technol., 1\u201314.","DOI":"10.1080\/10667857.2020.1868209"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/j.actbio.2011.01.011","article-title":"Gradient biomaterials for soft-to-hard interface tissue engineering","volume":"7","author":"Seidi","year":"2011","journal-title":"Acta Biomater."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s10934-018-0644-x","article-title":"Preparation and characterization of PCL-coated porous hydroxyapatite scaffolds in the presence of MWCNTs and graphene for orthopedic applications","volume":"26","author":"Atmaca","year":"2019","journal-title":"J. Porous Mater."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18710","DOI":"10.1016\/j.ceramint.2019.06.097","article-title":"Drug loaded electrospun polymer\/ceramic composite nanofibrous coatings on titanium for implant related infections","volume":"45","author":"Kiran","year":"2019","journal-title":"Ceram. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"015307","DOI":"10.1088\/2053-1591\/abd826","article-title":"Electrospun fabrication and direct coating of bio-degradable fibrous composite on orthopedic Titanium implant: Synthesis and Characterizations","volume":"8","year":"2021","journal-title":"Mater. Res. Express"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1002\/jbm.a.36709","article-title":"Impact of crystallinity and crystal size of nanostructured carbonated hydroxyapatite on pre-osteoblast in vitro biocompatibility","volume":"107","author":"Anjos","year":"2019","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s12010-019-03015-z","article-title":"In Vitro Fabrication and Biocompatibility Assay of a Biomimetic Osteoblastic Niche","volume":"189","author":"Song","year":"2019","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.mattod.2013.11.017","article-title":"Bone tissue engineering using 3D printing","volume":"16","author":"Bose","year":"2013","journal-title":"Mater. Today"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1023\/B:ABME.0000017544.36001.8e","article-title":"Polymeric Scaffolds for Bone Tissue Engineering","volume":"32","author":"Liu","year":"2004","journal-title":"Ann. Biomed. Eng."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.matdes.2017.03.051","article-title":"Measurements of the mechanical response of unidirectional 3D-printed PLA","volume":"123","author":"Song","year":"2017","journal-title":"Mater. Des."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.compositesb.2019.03.076","article-title":"Integrated ternary bionanocomposites with superior mechanical performance via the synergistic role of graphene and plasma treated carbon nanotubes","volume":"168","author":"Scaffaro","year":"2019","journal-title":"Compos. B. Eng."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ale\u0161, G., Filov\u00e1, E., Nov\u00e1k, M., Kronek, J., Chlup, H., Buzgo, M., Blahnov\u00e1, V., Luk\u00e1\u0161ov\u00e1, V., Barto\u0161, M., and Ne\u010das, A. (2017). Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary commercial 3D printer. J. Biol. Eng., 11.","DOI":"10.1186\/s13036-017-0074-3"},{"key":"ref_17","first-page":"130","article-title":"Effect of TiO2 Nanotubes Developed on Pure Titanium Substrates on the Mechanical Performance of Titanium-Titanium Single-Lap Adhesive Joints","volume":"28","author":"Papanicolaou","year":"2016","journal-title":"Cienc. Tecnol. Mater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1007\/s10853-012-6338-x","article-title":"A combined statistical and microscopic analysis of TiO2 nanotubes synthesized under different electrochemical anodizing conditions","volume":"47","author":"Portan","year":"2012","journal-title":"J. Mater. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kostopoulos, V., Kotrotsos, A., Fouriki, K., Kalarakis, A., and Portan, D.V. (2020). Fabrication and Characterization of Polyetherimide Electrospun Scaffolds Modified with Graphene Nano-Platelets and Hydroxyapatite Nano-Particles. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020583"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1002\/jbm.a.34188","article-title":"On the biocompatibility between TiO2 nanotubes layer and human osteoblasts","volume":"100A","author":"Portan","year":"2012","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"303","DOI":"10.37358\/MP.18.3.5018","article-title":"A Step Forward Standardization of Biocompatibility Testing on Tissue Culture Polystyrene","volume":"55","author":"Feier","year":"2018","journal-title":"Mater. Plast."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1801353","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. Healthc. Mater."},{"key":"ref_23","unstructured":"Decuir, F., Phelan, K., and Hollins, B.C. (2016, January 11\u201313). 32nd Southern Biomedical Engineering Conference (SBEC). 32nd Southern Biomedical Engineering Conference (SBEC), Shreveport, LA, USA."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1080\/03008207.2018.1499732","article-title":"3D-printed poly(lactic acid) scaffolds for trabecular bone repair and regeneration: Scaffold and native bone characterization","volume":"60","author":"Velioglu","year":"2019","journal-title":"Connect. Tissue Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.matlet.2018.03.205","article-title":"Effect of porous structure and pore size on mechanical strength of 3D-printed comby scaffolds","volume":"223","author":"Zhao","year":"2018","journal-title":"Mater. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1002\/app.22095","article-title":"Water absorption mechanism and some anomalous effects on the mechanical and viscoelastic behavior of an epoxy system","volume":"99","author":"Papanicolaou","year":"2006","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hua, W., Kar, P., Roy, P., Bu, L., Shoute, L.C.T., Kumar, P., and Shankar, K. (2018). Resistance of Superhydrophobic Surface-Functionalized TiO2 Nanotubes to Corrosion and Intense Cavitation. Nanomaterials, 8.","DOI":"10.3390\/nano8100783"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.apsusc.2016.01.010","article-title":"Surface wettability of TiO2 nanotube arrays prepared by electrochemical anodization","volume":"388","author":"Liu","year":"2016","journal-title":"Appl. Surf. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.snb.2018.10.105","article-title":"Electrochemical sensor for alkaline phosphatase as biomarker for clinical and in vitro applications","volume":"281","author":"Sappia","year":"2019","journal-title":"Sens. Actuators B Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s11431-018-9313-3","article-title":"Regulation of osteoblast functions on titanium surfaces with different micro\/nanotopographies and compositions","volume":"62","author":"He","year":"2019","journal-title":"Sci. China Technol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Portan, D.V., Deligianni, D.D., Papanicolaou, G.C., Kostopoulos, V., Psarras, G.C., and Tyllianakis, M. (2019). Combined Optimized Effect of a Highly Self-Organized Nanosubstrate and an Electric Field on Osteoblast Bone Cells Activity. Biomed. Res. Int.","DOI":"10.1155\/2019\/7574635"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1002\/jbm.a.36265","article-title":"Modeling of the interaction between osteoblasts and biocompatible substrates as a function of adhesion strength","volume":"106","author":"Portan","year":"2018","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1002\/jbm.a.31977","article-title":"Resorbable polymeric scaffolds for bone tissue engineering: The influence of their microstructure on the growth of human osteoblast-like MG 63 cells","volume":"89","author":"Pamula","year":"2009","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fujioka-Kobayashi, M., Katagiri, H., Kono, M., Schaller, B., Iizuka, T., and Safi, A.F. (2021). The impact of the size of bone substitute granules on macrophage and osteoblast behaviors in vitro. Clin. Oral Investig.","DOI":"10.1007\/s00784-021-03804-z"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"78","DOI":"10.29252\/ibj.25.2.78","article-title":"Increased Osteogenic Potential of Pre-Osteoblasts on Three-Dimensional Printed Scaffolds Compared to Porous Scaffolds for Bone Regeneration","volume":"25","author":"Zamani","year":"2021","journal-title":"Iran. Biomed. J."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/13\/5\/682\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:27:54Z","timestamp":1760160474000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/13\/5\/682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["polym13050682"],"URL":"https:\/\/doi.org\/10.3390\/polym13050682","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,24]]}}}