Poly(dopamine)-Assisted Immobilization of Arg-Gly-Asp Peptides, Hydroxyapatite, and Bone Morphogenic Protein-2 on Titanium to Improve the Osteogenesis of Bone Marrow Stem Cells
Abstract
Osteointegration of titanium implants in bone defects is clinically important for long-term performance of orthopaedic implants. In this work, we developed a facile and effective "one-pot" deposition method based on dopamine polymerization for the development of cell-adhesive, osteoconductive, and osteoinductive titanium implants. Arg-Gly-Asp (RGD)-conjugated polymers, hydroxyapatite (HAp) nanoparticles, and bone morphogenic protein-2 (BMP-2) were mixed with an alkaline dopamine solution, and then, titanium substrates were immersed in the mixture for an hour. During poly(dopamine) coating, the three types of bioactive substances were immobilized on the titanium surfaces. Our results indicate that RGD conjugation enhanced the adhesion of human bone marrow stem cell line, while HAp incorporation facilitated cellular osteodifferentiation. The immobilization of BMP-2 induced the osteogenesis of the stem cells, indicated by reverse-transcriptase polymerase chain reaction (RT-PCR) analysis. The mineralization on the deposited substrates was also enhanced greatly. This functionalized layer on titanium substrate promoted mesenchymal stem cell to osteoblast and improved osteogenic differentiation and mineralization. In conclusion, the surface modification method shows a great potential for enhancement of osteointegration of orthopaedic and dental implants.
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PDA's multimodal adhesion mechanism enables it to firmly attach to nearly all classes of material surfaces, irrespective of their chemical composition or surface wettability, including hydrophilic and hydrophobic as well as organic and inorganic substrates.
“This multimodal adhesion mechanism enables PDA to firmly attach to nearly all classes of material surfaces, irrespective of their chemical composition or surface wettability, including both hydrophilic and hydrophobic as well as organic and inorganic substrates.”
From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [4]
Deposition of a nanoscale PDA coating on titanium or zirconia implants markedly enhances their surface bioactivity and overall biological performance.
“Numerous studies have demonstrated that the deposition of a nanoscale PDA coating on titanium or zirconia implants markedly enhances their surface bioactivity and overall biological performance.”
From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [4]
After seven days of culture, the cell number on Ti-DA/RGD/HA was about 4.42 × 104 cells/cm2, higher than on Ti-DA/HA (2.65 × 104 cells/cm2).
“They found that after seven days of culture, the cell number on Ti-DA/RGD/HA was about 4.42 × 104 cells/cm2, higher than the Ti-DA/HA (2.65 × 104 cells/cm2) only.”
From Strategies for Using Polydopamine to Induce Biomineralization of Hydroxyapatite on Implant Materials for Bone Tissue Engineering (2020) · cites this paper as [51]
The improvement of cell adhesion and proliferation was largely due to PDA deposition and RGD incorporation but not HA nanoparticles alone.
“It is worth to mention that the improvement of cell adhesion and proliferation was largely due to PDA deposition and RGD incorporation but not HA nanoparticles alone.”
From Strategies for Using Polydopamine to Induce Biomineralization of Hydroxyapatite on Implant Materials for Bone Tissue Engineering (2020) · cites this paper as [51]
Elevated expression levels of BSP, RunX2, ALP, OPN, and OCN suggest improved osteogenic differentiation.
“Elevated expression levels of BSP (bone sialoprotein), RunX2 (Runt-related transcription factor 2), ALP, OPN (osteopontin), and OCN (osteocalcin) further suggests the improved osteogenic differentiation.”
From Strategies for Using Polydopamine to Induce Biomineralization of Hydroxyapatite on Implant Materials for Bone Tissue Engineering (2020) · cites this paper as [51]
Cell proliferation was not much affected by the incorporation of HA nanoparticles.
“Of note, cell proliferation was not much affected by the incorporation of HA nanoparticles.”
From Strategies for Using Polydopamine to Induce Biomineralization of Hydroxyapatite on Implant Materials for Bone Tissue Engineering (2020) · cites this paper as [51]
A polydopamine-coated surface can enhance attachment of NT3T3 fibroblast cells.
“Additionally, the PDA coated surface can enhance the attachment of NT3T3 fibroblast cell [73, 74].”
From Polydopamine-Assisted Surface Modification for Bone Biosubstitutes (2016) · cites this paper as [73]
Cites
The effect of VEGF functionalization of titanium on endothelial cells in vitro
Poh, C. K., Shi, Z., Lim, T. Y., Neoh, K. G., & Wang, W. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2009.11.042 · Cited by 236 · see citing works
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Polydopamine-Assisted Surface Modification for Bone Biosubstitutes
Huang, S., Liang, N., Hu, Y., Zhou, X., & Abidi, N. (2016) · BioMed Research International · doi:10.1155/2016/2389895 · Cited by 97 · see citing works
“It has been reported that PDA enhances the proliferation and calcium deposition of osteoblast cells and the effect can be further strengthened in the combination of growth factors [71, 72].”
BackgroundKaushik, N., Nhat Nguyen, L., Kim, J. H., Choi, E. H., & Kumar Kaushik, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186544 · Cited by 76 · see citing works
“This cell adhesive surface modification technique presents a great perspective for developing orthopedics and tooth implants, through improving cell adhesion, osteogenic differentiation, and mineralization [51].”
BackgroundYang, Z., Liu, M., Yang, Y., Zheng, M., Yang, Y., Liu, X., & Tan, J. (2020) · RSC Advances · doi:10.1039/c9ra08575k · Cited by 58 · see citing works
Yang, Z., Song, W., Lv, L., Zhai, S., Liu, Y., Cui, H., Li, X., Gao, F., & Chu, S. (2026) · International Journal of Nanomedicine · doi:10.2147/ijn.s611922
“4,6 In the context of oral medicine, such universal adhesion allows PDA to be readily applied for surface functionalization of titanium implants, zirconia ceramics, resin-based composites, polymer membranes, and related materials.”
- Authors
- Chien, C.-Y., & Tsai, W.-B.
- Affiliations
- National Taiwan University (TW)
- Corresponding author
- Tsai, Wei-Bor
- ORCID
- Tsai, Wei-Bor
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-07-24
- Volume
- 5
- Issue
- 15
- Pages
- 6975-6983
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2323258862
- Cited by
- 202
- References
- 1
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 15 · 2021: 16 · 2020: 17 · 2019: 17 · 2018: 20 · 2017: 21 · 2016: 26 · 2015: 22 · 2014: 22 · 2013: 1
- FWCI
- 13.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ottawa Hospital Research Institute
- National Science Council
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Physical Sciences › Engineering › Mechanical Engineering › Surface Treatment and Coatings
- Keywords
- polydopamine, RGD peptide, hydroxyapatite nanoparticles, BMP-2, titanium implants, osseointegration, bone marrow-derived stem cells, osteogenic differentiation, mineralization, surface modification, orthopedic implants, dental implants
- MeSH terms
- Animals, Arginine, Aspartic Acid, Bone Marrow Cells, Cell Adhesion, Cell Differentiation, Glycine, Humans, Hydroxyapatites, Indoles, Oligopeptides, Osteogenesis, Polymers, Surface Properties, Titanium, Osseointegration, Reverse Transcriptase Polymerase Chain Reaction, Mice, Nanoparticles, Bone Morphogenetic Protein 2
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