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. 2025 May-Jun;39(3):1786-1798.
doi: 10.21873/invivo.13980.

Controlling Cellular Behavior by Surface Design of Titanium-based Biomaterials

Tonya Andreeva  1 , Osman Akbas  2 , Anne Jahn  3 , Andreas Greuling  2 , Andreas Winkel  2 , Meike Stiesch  2 , Rumen Krastev  4
Affiliations

Controlling Cellular Behavior by Surface Design of Titanium-based Biomaterials

Tonya Andreeva et al. In Vivo. 2025 May-Jun.

Abstract

Background/aim: Titanium alloys, especially Ti6Al4V, are widely used in orthopedic and dental implants. Additive manufacturing has emerged as an innovative fabrication technique for titanium implants, gradually replacing traditional machining methods. A notable feature of additively manufactured medical devices is their considerable surface heterogeneity and roughness. Coating these materials to achieve physical and chemical uniformity is essential for enhancing biocompatibility. This study evaluates the combined effect of surface roughness (ranging from sub-micrometer to micrometer scale) and three nanometer-thick polyelectrolyte multilayer coatings on protein adsorption, as well as the adhesion and proliferation of normal human osteoblasts.

Materials and methods: The adhesion of human osteoblasts to various substrates (either uncoated or coated) was quantified using a lactate dehydrogenase assay and scanning electron microscopy. The surface density of adsorbed human serum albumin was analyzed by the Bradford assay.

Results: Application of polyelectrolyte multilayer coatings significantly increased the hydrophilicity of titanium substrates without altering their sub-micrometer and micrometer roughness or topography. The coatings rich in reactive amino groups were found to enhance the adsorption of human serum albumin and promote the adhesion of osteoblasts.

Conclusion: The chemical composition of the surface, particularly the presence of free primary amino groups, significantly affects cellular behavior in machined, sand-blasted, and additively manufactured titanium materials, while the impact of surface roughness appears secondary. No correlation was observed between surface hydrophilicity and protein adsorption or cell attachment.

Keywords: Titanium alloys; additive manufacturing; biomaterials; human osteoblasts adhesion and proliferation; implant surface roughness; polyelectrolyte multilayer coatings; surface modification.

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Conflict of interest statement

All Authors of the manuscript declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Scanning electron micrographs of (A) machined titanium (MTi), (B) sand-blasted titanium (SBTi), and (C) additively manufactured titanium (AMTi) disks with roughness profiles (D) obtained with an optical profilometer.
Figure 2
Figure 2
Proportion of attached human osteoblasts after 24 h of cultivation, reflecting the extent of cell adhesion, and after 72 h of cultivation, reflecting the extent of cell proliferation, examined on machined (MTi), sand‐blasted (SBTi), and additively manufactured (AMTi) titanium disks, uncoated (A) and coated with polystyrene sulfonate (PSS)/polyallylamine hydrochloride (PAH) (B), polyacrylic acid (PAA)/PAH (C), and hyaluronic acid (HA)/chitosan (Ch) (D). *Significantly different at p<0.05, **p<0.01 from the control uncoated Ti6Al4V of the same type. The data presented are averages obtained from eight samples.
Figure 3
Figure 3
Scanning electron micrographs representing the morphology of human osteoblasts attached to machined (MTi), sand‐blasted (SBTi), and additively manufactured (AMTi) titanium disks uncoated and coated with polystyrene sulfonate (PSS)/polyallylamine hydrochloride (PAH), polyacrylic acid (PAA)/PAH, and hyaluronic acid (HA)/chitosan (Ch) after 24 h of cultivation. Magnification 1,200×, the white bar corresponds to 20 μm.
See this image and copyright information in PMC

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