{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:07:39Z","timestamp":1776769659710,"version":"3.51.2"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2016,12,7]],"date-time":"2016-12-07T00:00:00Z","timestamp":1481068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Scaffolds are physical substrates for cell attachment, proliferation, and differentiation, ultimately leading to the regeneration of tissues. They must be designed according to specific biomechanical requirements, i.e., certain standards in terms of mechanical properties, surface characteristics, porosity, degradability, and biocompatibility. The optimal design of a scaffold for a specific tissue strongly depends on both materials and manufacturing processes, as well as surface treatment. Polymeric scaffolds reinforced with electro-active particles could play a key role in tissue engineering by modulating cell proliferation and differentiation. This paper investigates the use of an extrusion-based additive manufacturing system to produce poly(\u03b5-caprolactone) (PCL)\/pristine graphene scaffolds for bone tissue applications and the influence of chemical surface modification on their biological behaviour. Scaffolds with the same architecture but different concentrations of pristine graphene were evaluated from surface property and biological points of view. Results show that the addition of pristine graphene had a positive impact on cell viability and proliferation, and that surface modification leads to improved cell response.<\/jats:p>","DOI":"10.3390\/ma9120992","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T10:39:01Z","timestamp":1481193541000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":289,"title":["Enhancing the Hydrophilicity and Cell Attachment of 3D Printed PCL\/Graphene Scaffolds for Bone Tissue Engineering"],"prefix":"10.3390","volume":"9","author":[{"given":"Weiguang","family":"Wang","sequence":"first","affiliation":[{"name":"Manchester Institute of Biotechnology, School of Mechanical, Aerospace and Civil Engineering, University of Manchester, Manchester M13 9PL, UK"}]},{"given":"Guilherme","family":"Caetano","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, School of Mechanical, Aerospace and Civil Engineering, University of Manchester, Manchester M13 9PL, UK"},{"name":"Department of Internal Medicine, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto, SP 14049-900, Brazil"}]},{"given":"William","family":"Ambler","sequence":"additional","affiliation":[{"name":"Bio\/Active Materials Group, School of Materials, The University of Manchester, Manchester M13 9PL, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1112-8619","authenticated-orcid":false,"given":"Jonny","family":"Blaker","sequence":"additional","affiliation":[{"name":"Bio\/Active Materials Group, School of Materials, The University of Manchester, Manchester M13 9PL, UK"}]},{"given":"Marco","family":"Frade","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto, SP 14049-900, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4051-110X","authenticated-orcid":false,"given":"Parthasarathi","family":"Mandal","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, School of Mechanical, Aerospace and Civil Engineering, University of Manchester, Manchester M13 9PL, UK"}]},{"given":"Carl","family":"Diver","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, School of Mechanical, Aerospace and Civil Engineering, University of Manchester, Manchester M13 9PL, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3683-726X","authenticated-orcid":false,"given":"Paulo","family":"B\u00e1rtolo","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, School of Mechanical, Aerospace and Civil Engineering, University of Manchester, Manchester M13 9PL, UK"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/17452750903476288","article-title":"Biomanufacturing for tissue engineering: Present and future trends","volume":"4","author":"Bartolo","year":"2009","journal-title":"Virtual Phys. Prototyp."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cirp.2012.05.005","article-title":"Biomedical production of implants by additive electro-chemical and physical processes","volume":"61","author":"Bartolo","year":"2012","journal-title":"CIRP Ann. Manuf. Technol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1080\/17452759.2015.1097053","article-title":"Extrusion-based additive manufacturing of PEEK for biomedical applications","volume":"10","author":"Vaezi","year":"2015","journal-title":"Virtual Phys. Prototyp."},{"key":"ref_4","unstructured":"B\u00e1rtolo, P.J., Almeida, H.A., Rezende, R.A., Laoui, T., and Bidanda, B. (2008). Virtual Prototyping & Bio Manufacturing in Medical Applications, Springer."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1504\/IJCAT.2009.026664","article-title":"Rapid prototyping and manufacturing for tissue engineering scaffolds","volume":"36","author":"Almeida","year":"2009","journal-title":"Int. J. Comput. Appl. Technol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/17452759.2013.873337","article-title":"Multiple initiators and dyes for continuous Digital Light Processing (cDLP) additive manufacture of resorbable bone tissue engineering scaffolds: A new method and new material to fabricate resorbable scaffold for bone tissue engineering via continuous Digital Light Processing","volume":"9","author":"Dean","year":"2014","journal-title":"Virtual Phys. Prototyp."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, S., Lee, J.M., and Yeong, W.Y. (2015). Smart hydrogels for 3D bioprinting. Int. J. Bioprint., 1.","DOI":"10.18063\/IJB.2015.01.005"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, M., He, J., Liu, Y., Li, M., Li, D., and Jin, Z. (2015). The trend towards in vivo bioprinting. Int. J. Bioprint., 1.","DOI":"10.18063\/IJB.2015.01.001"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/17452759.2014.979557","article-title":"A preliminary model of time-pressure dispensing system for bioprinting based on printing and material parameters: This paper reports a method to predict and control the width of hydrogel filament for bioprinting applications","volume":"10","author":"Lee","year":"2015","journal-title":"Virtual Phys. Prototyp."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/17452759.2015.1097054","article-title":"3D printing of smart materials: A review on recent progresses in 4D printing","volume":"10","author":"Khoo","year":"2015","journal-title":"Virtual Phys. Prototyp."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.matlet.2016.05.152","article-title":"Cellularized versus decellularized scaffolds for bone regeneration","volume":"182","author":"Caetano","year":"2016","journal-title":"Mater. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.actbio.2015.11.012","article-title":"In vitro and in vivo bone formation potential of surface calcium phosphate-coated polycaprolactone and polycaprolactone\/bioactive glass composite scaffolds","volume":"30","author":"Poh","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5997","DOI":"10.1016\/j.actbio.2012.12.031","article-title":"Improved osteoblast cell affinity on plasma-modified 3-D extruded PCL scaffolds","volume":"9","author":"Domingos","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.matlet.2014.06.132","article-title":"Collagen surface modified poly (\u03b5-caprolactone) scaffolds with improved hydrophilicity and cell adhesion properties","volume":"134","author":"Sousa","year":"2014","journal-title":"Mater. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.progpolymsci.2010.07.005","article-title":"Recent advances in graphene based polymer composites","volume":"35","author":"Kuilla","year":"2010","journal-title":"Prog. Polym. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.biomaterials.2004.03.010","article-title":"Laser surface modification of poly (\u03b5-caprolactone) (PCL) membrane for tissue engineering applications","volume":"26","author":"Tiaw","year":"2005","journal-title":"Biomaterials"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1002\/jbm.a.32633","article-title":"Surface modification of PCL-TCP scaffolds in rabbit calvaria defects: Evaluation of scaffold degradation profile, biomechanical properties and bone healing patterns","volume":"93","author":"Yeo","year":"2010","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.msec.2006.03.010","article-title":"Effect of stiffness of polycaprolactone (PCL) membrane on cell proliferation","volume":"27","author":"Tan","year":"2007","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1063\/1.2774096","article-title":"Graphene: Exploring carbon flatland","volume":"60","author":"Geim","year":"2007","journal-title":"Phys. Today"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1021\/nl080604h","article-title":"Synthesis of water soluble graphene","volume":"8","author":"Si","year":"2008","journal-title":"Nano Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cplett.2007.07.059","article-title":"Soluble graphene derived from graphite fluoride","volume":"445","author":"Worsley","year":"2007","journal-title":"Chem. Phys. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7720","DOI":"10.1021\/ja060680r","article-title":"Solution properties of graphite and graphene","volume":"128","author":"Niyogi","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1021\/am200428v","article-title":"Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblasts","volume":"3","author":"Liao","year":"2011","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_24","first-page":"1","article-title":"Biocompatibility of graphene oxide","volume":"6","author":"Wang","year":"2011","journal-title":"Nanoscale Res. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.1021\/nn1007176","article-title":"Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells","volume":"4","author":"Zhang","year":"2010","journal-title":"Acs Nano"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Park, S.Y., Park, J., Sim, S.H., Sung, M.G., Kim, K.S., Hong, B.H., and Hong, S. (2011). Enhanced differentiation of human neural stem cells into neurons on graphene. Adv. Mater., 23.","DOI":"10.1002\/adma.201101503"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9374","DOI":"10.1016\/j.biomaterials.2011.08.065","article-title":"The promotion of neurite sprouting and outgrowth of mouse hippocampal cells in culture by graphene substrates","volume":"32","author":"Li","year":"2011","journal-title":"Biomaterials"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, W., Caetano, G.F., Chiang, W.H., Braz, A.L., Blaker, J.J., Frade, M.A., and Bartolo, P.J. (2016). Morphological, mechanical and biological assessment of PCL\/pristine graphene scaffolds for bone regeneration. Int. J. Bioprint., 2.","DOI":"10.18063\/IJB.2016.02.009"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.msec.2015.01.100","article-title":"Polybiguanide (PHMB) loaded in PLA scaffolds displaying high hydrophobic, biocompatibility and antibacterial properties","volume":"50","author":"Llorens","year":"2015","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8401","DOI":"10.1021\/acsnano.5b03220","article-title":"Thickness-dependent hydrophobicity of epitaxial graphene","volume":"9","author":"Munz","year":"2015","journal-title":"ACS Nano"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7334","DOI":"10.1021\/nn202190c","article-title":"Origin of enhanced stem cell growth and differentiation on graphene and graphene oxide","volume":"5","author":"Lee","year":"2011","journal-title":"ACS Nano"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8674","DOI":"10.3390\/ma8125481","article-title":"Graphene-based materials for stem cell aaplications","volume":"8","author":"Kim","year":"2015","journal-title":"Materials"},{"key":"ref_33","unstructured":"Chua, C.K., Lau, G.K., Moon, S.K., Zhang, Y.L., Zhou, K., and Zhou, Y.F. (2016). Design, Fabrication and Evaluation of PCL\/Graphene Scaffolds for Bone Regeneration, Proceedings of the 2nd International Conference on Progress in Additive Manufacturing, Singapore, 16\u201319 May 2016, Research Publishing."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.proeng.2015.07.010","article-title":"Osteogenic differentiation of adipose-derived mesenchymal stem cells into Polycaprolactone (PCL) scaffold","volume":"110","author":"Caetano","year":"2015","journal-title":"Procedia Eng."},{"key":"ref_35","first-page":"385","article-title":"Assay of mitochondrial functions by resazurin in vitro","volume":"25","author":"Zhang","year":"2004","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_36","first-page":"e4","article-title":"An Overview of Colorimetric Assay Methods Used to Assess Survival or Proliferation of Mammalian Cells","volume":"54","author":"Pugsley","year":"2011","journal-title":"Proc. West Pharmacol. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1046\/j.1440-1711.1999.00877.x","article-title":"Fluorescent dyes for lymphocyte migration and proliferation studies","volume":"77","author":"Parish","year":"1999","journal-title":"Immunol. Cell Boil."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1046\/j.1365-2818.2001.00854.x","article-title":"Segmentation of nuclei and cells using membrane related protein markers","volume":"201","author":"Malladi","year":"2001","journal-title":"J. Microsc."}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/9\/12\/992\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:28:09Z","timestamp":1760210889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/9\/12\/992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,7]]},"references-count":38,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["ma9120992"],"URL":"https:\/\/doi.org\/10.3390\/ma9120992","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,7]]}}}