{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T12:18:56Z","timestamp":1772540336283,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Diamond is a promising material for the biomedical field, mainly due to its set of characteristics such as biocompatibility, strength, and electrical conductivity. Diamond can be synthesised in the laboratory by different methods, is available in the form of plates or films deposited on foreign substrates, and its morphology varies from microcrystalline diamond to ultrananocrystalline diamond. In this review, we summarise some of the most relevant studies regarding the adhesion of cells onto diamond surfaces, the consequent cell growth, and, in some very interesting cases, the differentiation of cells into neurons and oligodendrocytes. We discuss how different morphologies can affect cell adhesion and how surface termination can influence the surface hydrophilicity and consequent attachment of adherent proteins. At the end of the review, we present a brief perspective on how the results from cell adhesion and biocompatibility can make way for the use of diamond as biointerface.<\/jats:p>","DOI":"10.3390\/molecules28041626","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T03:57:16Z","timestamp":1675828636000},"page":"1626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Gemstone Cyborg: How Diamond Films Are Creating New Platforms for Cell Regeneration and Biointerfacing"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4560-6172","authenticated-orcid":false,"given":"N\u00e1dia E.","family":"Santos","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Instituto de Telecomunica\u00e7\u00f5es and University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9271-207X","authenticated-orcid":false,"given":"Joana C.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Instituto de Telecomunica\u00e7\u00f5es and University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4460-970X","authenticated-orcid":false,"given":"Susana Santos","family":"Braga","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20170382","DOI":"10.1098\/rsif.2017.0382","article-title":"Diamond thin films: Giving biomedical applications a new shine","volume":"14","author":"Nistor","year":"2017","journal-title":"J. R. Soc. Interface"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10134","DOI":"10.1039\/C9TC03381E","article-title":"Diamond surface functionalization: From gemstone to photoelectrochemical applications","volume":"7","author":"Raymakers","year":"2019","journal-title":"J. Mater. Chem. C"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0167-5729(97)80002-7","article-title":"Hydrogen-terminated diamond surfaces and interfaces","volume":"26","author":"Kawarada","year":"1996","journal-title":"Surf. Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Santos, N.E., Figueira, F., Neto, M., Paz, F.A.A., Braga, S.S., and Mendes, J.C. (2022). Diamonds for life: Developments in sensors for biomolecules. Appl. Sci., 12.","DOI":"10.3390\/app12063000"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.1016\/j.biomaterials.2009.03.058","article-title":"The effect of ultra-nanocrystalline diamond films on the proliferation and differentiation of neural stem cells","volume":"30","author":"Chen","year":"2009","journal-title":"Biomaterials"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5575","DOI":"10.1016\/j.biomaterials.2010.03.061","article-title":"Induction and regulation of differentiation in neural stem cells on ultra-nanocrystalline diamond films","volume":"31","author":"Chen","year":"2010","journal-title":"Biomaterials"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"R713","DOI":"10.1016\/j.cub.2017.05.064","article-title":"Animal communication: When I\u2019m calling you, will you answer too?","volume":"27","author":"Vickers","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.diamond.2012.01.023","article-title":"Spatially controlling neuronal adhesion on CVD diamond","volume":"23","author":"May","year":"2012","journal-title":"Diam. Relat. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.1016\/j.biomaterials.2003.11.006","article-title":"Ordered growth of neurons on diamond","volume":"25","author":"Specht","year":"2004","journal-title":"Biomaterials"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1140\/epje\/i2009-10520-9","article-title":"On diamond surface properties and interactions with neurons","volume":"30","author":"Ariano","year":"2009","journal-title":"Eur. Phys. J. E"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"588","DOI":"10.3390\/jfb3030588","article-title":"Cell growth on different types of ultrananocrystalline diamond thin films","volume":"3","author":"Shi","year":"2012","journal-title":"J. Funct. Biomater."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5615","DOI":"10.1021\/la070037y","article-title":"Cell adhesion properties on photochemically functionalized diamond","volume":"23","author":"Chong","year":"2007","journal-title":"Langmuir"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.msec.2015.12.041","article-title":"The influence of sterilization on nitrogen-included ultrananocrystalline diamond for biomedical applications","volume":"61","author":"Tong","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.actbio.2008.08.015","article-title":"Cytotoxicity evaluation of nanocrystalline diamond coatings by fibroblast cell cultures","volume":"5","author":"Amaral","year":"2009","journal-title":"Acta Biomater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.3390\/s90503549","article-title":"Micro-pattern guided adhesion of osteoblasts on diamond surfaces","volume":"9","author":"Rezek","year":"2009","journal-title":"Sensors"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Grausova, L., Kromka, A., Burdikova, Z., Eckhardt, A., Rezek, B., Vacik, J., Haenen, K., Lisa, V., and Bacakova, L. (2011). Enhanced growth and osteogenic differentiation of human osteoblast-like cells on boron-doped nanocrystalline diamond thin films. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020943"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/jbm.a.31742","article-title":"Nanocrystalline diamond: In vitro biocompatibility assessment by MG63 and human bone marrow cells cultures","volume":"87A","author":"Amaral","year":"2008","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.1016\/j.biomaterials.2008.07.023","article-title":"The surface properties of nanocrystalline diamond and nanoparticulate diamond powder and their suitability as cell growth support surfaces","volume":"29","author":"Lechleitner","year":"2008","journal-title":"Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.cobme.2019.03.002","article-title":"Biocompatibility and functionalization of diamond for neural applications","volume":"10","author":"Yang","year":"2019","journal-title":"Curr. Opin. Biomed. Eng."},{"key":"ref_20","first-page":"267","article-title":"Evolutionary selection, a principle governing growth orientation in vapour-deposited layers","volume":"22","year":"1967","journal-title":"Philips Res. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"374017","DOI":"10.1088\/0022-3727\/43\/37\/374017","article-title":"Diamond growth by chemical vapour deposition","volume":"43","author":"Gracio","year":"2010","journal-title":"J. Phys. D Appl. Phys."},{"key":"ref_22","first-page":"211","article-title":"Nanocrystalline diamond films","volume":"29","author":"Gruen","year":"1999","journal-title":"Annu. Rev. Mater. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.diamond.2005.12.009","article-title":"Comparison of the growth and properties of ultrananocrystalline diamond and nanocrystalline diamond","volume":"15","author":"Williams","year":"2006","journal-title":"Diam. Relat. Mater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"235429","DOI":"10.1103\/PhysRevB.76.235429","article-title":"Surface chemistry and bonding configuration of ultrananocrystalline diamond surfaces and their effects on nanotribological properties","volume":"76","author":"Sumant","year":"2007","journal-title":"Phys. Rev. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1177\/096368970000900202","article-title":"Neural stem cells: From cell biology to cell replacement","volume":"9","author":"Armstrong","year":"2000","journal-title":"Cell Transplant."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1042\/CS20040276","article-title":"Neural stem cells and cell replacement therapy: Making the right cells","volume":"108","author":"Bithell","year":"2004","journal-title":"Clin. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1091\/mbc.12.7.1937","article-title":"Modulation of cell-substrate adhesion by arachidonic acid: Lipoxygenase regulates cell spreading and ERK1\/2-inducible cyclooxygenase regulates cell migration in NIH-3T3 fibroblasts","volume":"12","author":"Stockton","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5813","DOI":"10.1016\/j.biomaterials.2006.07.031","article-title":"Real-time analysis of cell\u2013surface adhesive interactions using thickness shear mode resonator","volume":"27","author":"Hong","year":"2006","journal-title":"Biomaterials"},{"key":"ref_29","unstructured":"Hoffman, R., Benz, E.J., Silberstein, L.E., Heslop, H.E., Weitz, J.I., Anastasi, J., Salama, M.E., and Abutalib, S.A. (2018). Hematology, Elsevier. [7th ed.]. Chapter 12."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/cvde.200700037","article-title":"The CVD of Nanodiamond Materials","volume":"14","author":"Butler","year":"2008","journal-title":"Chem. Vap. Depos."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/0142-9612(96)81418-9","article-title":"Benign response to particles of diamond and SiC: Bone chamber studies of new joint replacement coating materials in rabbits","volume":"17","author":"Aspenberg","year":"1996","journal-title":"Biomaterials"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.tsf.2005.07.163","article-title":"Nanocrystalline diamond\/amorphous carbon composite films for applications in tribology, optics and biomedicine","volume":"494","author":"Popov","year":"2006","journal-title":"Thin Solid Films"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4547","DOI":"10.1016\/j.biomaterials.2006.04.036","article-title":"Strong binding of bioactive BMP-2 to nanocrystalline diamond by physisorption","volume":"27","author":"Kloss","year":"2006","journal-title":"Biomaterials"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/dvdy.21753","article-title":"Brain-specific 1B promoter of FGF1 gene facilitates the isolation of neural stem\/progenitor cells with self-renewal and multipotent capacities","volume":"238","author":"Hsu","year":"2009","journal-title":"Dev. Dyn."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nmeth758","article-title":"Neural stem cells and neurospheres\u2014Re-evaluating the relationship","volume":"2","author":"Reynolds","year":"2005","journal-title":"Nat. Methods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"056022","DOI":"10.1088\/1741-2560\/10\/5\/056022","article-title":"Patterned neuronal networks using nanodiamonds and the effect of varying nanodiamond properties on neuronal adhesion and outgrowth","volume":"10","author":"Edgington","year":"2013","journal-title":"J. Neural Eng."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Amini, S., and White, M.K. (2021). Neuronal Cell Culture: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-0716-1437-2"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.diamond.2004.11.021","article-title":"Cellular adhesion and neuronal excitability on functionalised diamond surfaces","volume":"14","author":"Ariano","year":"2005","journal-title":"Diam. Relat. Mater."},{"key":"ref_39","first-page":"e60168","article-title":"Primary culture of neurons isolated from embryonic mouse cerebellum","volume":"152","author":"Shabanipour","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.biomaterials.2015.04.050","article-title":"Long-term culture of pluripotent stem-cell-derived human neurons on diamond\u2014A substrate for neurodegeneration research and therapy","volume":"61","author":"Nistor","year":"2015","journal-title":"Biomaterials"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fneng.2014.00017","article-title":"Nanocrystalline diamond surfaces for adhesion and growth of primary neurons, conflicting results and rational explanation","volume":"7","author":"Ojovan","year":"2014","journal-title":"Front. Neuroeng."},{"key":"ref_42","unstructured":"Majchrowicz, D., Ficek, M., Baran, T., W\u0105sowicz, M., Struk, P., and J\u0119drzejewska-Szczerska, M. (September, January 30). Diamond-based protective layer for optical biosensors. Proceedings of the Nanostructured Thin Films IX, San Diego, CA, USA."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6443","DOI":"10.1088\/0022-3727\/40\/20\/S21","article-title":"Diamond for bio-sensor applications","volume":"40","author":"Nebel","year":"2007","journal-title":"J. Phys. D Appl. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1557\/mrc.2017.62","article-title":"Diamond microelectrode arrays for in vitro neuronal recordings","volume":"7","author":"McDonald","year":"2017","journal-title":"MRS Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.msec.2014.10.018","article-title":"Microfabrication, characterization and in vivo MRI compatibility of diamond microelectrodes array for neural interfacing","volume":"46","author":"Warnking","year":"2015","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.biomaterials.2015.02.021","article-title":"3D-nanostructured boron-doped diamond for microelectrode array neural interfacing","volume":"53","author":"Piret","year":"2015","journal-title":"Biomaterials"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1039\/C6RA20207A","article-title":"Interfacing neurons on carbon nanotubes covered with diamond","volume":"7","author":"Seyock","year":"2017","journal-title":"RSC Adv."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5812","DOI":"10.1016\/j.biomaterials.2012.04.063","article-title":"Electrical stimulation of retinal ganglion cells with diamond and the development of an all diamond retinal prosthesis","volume":"33","author":"Hadjinicolaou","year":"2012","journal-title":"Biomaterials"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bendali, A., Agn\u00e8s, C., Meffert, S., Forster, V., Bongrain, A., Arnault, J.-C., Sahel, J.-A., Offenh\u00e4usser, A., Bergonzo, P., and Picaud, S. (2014). Distinctive glial and neuronal interfacing on nanocrystalline diamond. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092562"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Rousseau, L., Scorsone, E., Bendali, A., Djilas, M., Girard, H., Cottance, M., Joucla, S., Dubus, E., Degardin, J., and Yvert, B. (2013, January 16\u201320). Soft 3D retinal implants with diamond electrode a way for focal stimulation. Proceedings of the 2013 Transducers & Eurosensors XXVII: The 17th International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers & Eurosensors XXVII), Barcelona, Spain.","DOI":"10.1109\/Transducers.2013.6626996"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.biomaterials.2013.10.040","article-title":"An all-diamond, hermetic electrical feedthrough array for a retinal prosthesis","volume":"35","author":"Ganesan","year":"2014","journal-title":"Biomaterials"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s10544-015-9952-y","article-title":"Ultrananocrystalline diamond-CMOS device integration route for high acuity retinal prostheses","volume":"17","author":"Ahnood","year":"2015","journal-title":"Biomed. Microdevices"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1600003","DOI":"10.1002\/adbi.201600003","article-title":"Diamond devices for high acuity prosthetic vision","volume":"1","author":"Ahnood","year":"2017","journal-title":"Adv. Biosyst."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2000055","DOI":"10.1002\/adbi.202000055","article-title":"Laser driven miniature diamond implant for wireless retinal prostheses","volume":"4","author":"Ahnood","year":"2020","journal-title":"Adv. Biosyst."},{"key":"ref_55","unstructured":"Longitudinal Study of a Bionic Eye (2023, January 18). US National Institute of Health Clinical Trial, Registry NCT05158049, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05158049."},{"key":"ref_56","unstructured":"(2023, January 18). iBionics Clinical Timeline. Available online: http:\/\/ibionics.ca\/timeline\/."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1626\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:27:53Z","timestamp":1760120873000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1626"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,8]]},"references-count":56,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28041626"],"URL":"https:\/\/doi.org\/10.3390\/molecules28041626","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,8]]}}}