{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T04:09:32Z","timestamp":1783829372098,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Titanium alloy (Ti6Al4V) is one of the most prominent biomaterials for bone contact because of its ability to bear mechanical loading and resist corrosion. The success of Ti6Al4V implants depends on bone formation on the implant surface. Hence, implant coatings which promote adhesion, proliferation and differentiation of bone-forming cells are desirable. One coating strategy is by adsorption of biomacromolecules. In this study, Ti6Al4V substrates produced by additive manufacturing (AM) were coated with whey protein isolate (WPI) fibrils, obtained at pH 2, and heparin or tinzaparin (a low molecular weight heparin LMWH) in order to improve the proliferation and differentiation of bone-forming cells. WPI fibrils proved to be an excellent support for the growth of human bone marrow stromal cells (hBMSC). Indeed, WPI fibrils were resistant to sterilization and were stable during storage. This WPI-heparin-enriched coating, especially the LMWH, enhanced the differentiation of hBMSC by increasing tissue non-specific alkaline phosphatase (TNAP) activity. Finally, the coating increased the hydrophilicity of the material. The results confirmed that WPI fibrils are an excellent biomaterial which can be used for biomedical coatings, as they are easily modifiable and resistant to heat treatments. Indeed, the already known positive effect on osteogenic integration of WPI-only coated substrates has been further enhanced by a simple adsorption procedure.<\/jats:p>","DOI":"10.3390\/ijms23010139","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T10:16:18Z","timestamp":1640254578000},"page":"139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Heparin Enriched-WPI Coating on Ti6Al4V Increases Hydrophilicity and Improves Proliferation and Differentiation of Human Bone Marrow Stromal Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8290-289X","authenticated-orcid":false,"given":"Davide","family":"Facchetti","sequence":"first","affiliation":[{"name":"Engineering Department, Lancaster University, Lancaster LA1 4YW, UK"},{"name":"Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London W12 0BZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Hempel","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7579-965X","authenticated-orcid":false,"given":"Laurine","family":"Martocq","sequence":"additional","affiliation":[{"name":"Engineering Department, Lancaster University, Lancaster LA1 4YW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2791-3208","authenticated-orcid":false,"given":"Alan M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2964-9500","authenticated-orcid":false,"given":"Andrey","family":"Koptyug","sequence":"additional","affiliation":[{"name":"Department of Quality Technology, Mechanical Engineering & Mathematics, Mid Sweden University, 831 25 Ostersund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8061-3047","authenticated-orcid":false,"given":"Roman A.","family":"Surmenev","sequence":"additional","affiliation":[{"name":"Physical Materials Science and Composite Materials Centre, Research School of Chemistry & Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634050 Tomsk, Russia"},{"name":"Piezo- and Magnetoelectric Materials Research & Development Centre, Research School of Chemistry & Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Surmeneva","sequence":"additional","affiliation":[{"name":"Physical Materials Science and Composite Materials Centre, Research School of Chemistry & Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634050 Tomsk, Russia"},{"name":"Piezo- and Magnetoelectric Materials Research & Development Centre, Research School of Chemistry & Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E. L.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Engineering Department, Lancaster University, Lancaster LA1 4YW, UK"},{"name":"Materials Science Institute (MSI), Lancaster University, Lancaster, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8168","DOI":"10.3390\/ma7128168","article-title":"Biocompatibility of Advanced Manufactured Titanium Implants\u2014A Review","volume":"7","author":"Sidambe","year":"2014","journal-title":"Materials"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1021\/bm0609644","article-title":"Interactions of collagen types I and II with chondroitin sulfates A-C and their effect on osteoblast adhesion","volume":"8","author":"Douglas","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/jbm.a.31501","article-title":"Influence of collagen-fibril-based coatings containing decorin and biglycan on osteoblast behavior","volume":"84","author":"Douglas","year":"2008","journal-title":"J. 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