Mussel-inspired surface chemistry for multifunctional coatings

Amine-(thiol-) terminated methoxy-poly(ethylene glycol) (mPEG-SH/mPEG-NH2) with a polydopamine coating layer can improve cell adhesion behavior, although this biosubstitute material inhibits growth of NIH 3T3 cells.

“The amine-(thiol-) terminated methoxy-poly(ethylene glycol) (mPEG-SH/mPEG-NH2) with PDA coating layer can improve the cell adhesion behavior although this biosubstitute material exhibits an adverse effect of inhibiting the growth of NIH 3T3 cells [29].”

In oxidative self-polymerization, dopamine monomers undergo deprotonation and oxidation by dissolved oxygen, followed by intramolecular cyclization and subsequent polymerization.

“Under these conditions, dopamine monomers undergo deprotonation and oxidation by dissolved oxygen, followed by intramolecular cyclization and subsequent polymerization.”

Liquid-phase oxidative self-polymerization remains the most classical and widely adopted method for PDA fabrication.

“Among the available approaches, liquid-phase oxidative self-polymerization remains the most classical and widely adopted method for PDA fabrication.”

PDA's antibacterial and antibiofilm effects are associated with its catechol-rich chemical structure generating reactive oxygen species during oxidative processes, causing oxidative damage to bacterial cell membranes and genetic material, leading to bacterial inactivation.

“These effects are believed to be closely associated with its catechol-rich chemical structure, which can generate reactive oxygen species (ROS) during oxidative processes, leading to oxidative damage to bacterial cell membranes and genetic material, ultimately resulting in bacterial inactivation.1”

PDA has consistently been reported to exhibit biological inertness toward primary oral-derived cells.

“From a cytotoxicity standpoint, PDA has consistently been reported to exhibit biological inertness toward primary oral-derived cells.”

The bioadhesive application of DA has been documented, which highlights PDA for the same adhesive purpose because PDA is derived from DA and it has characteristics similar to DA.

“The bioadhesive application of DA has been documented, which highlights PDA for the same adhesive purpose because PDA is derived from DA and it has characteristics similar to DA [29].”

PDA-assisted surface modification is strongly subjected to the formation of PDA coating on the biomaterial interface caused by the oxidation reaction of dopamine (DA) in weak alkaline solution.

“PDA-assisted surface modification is strongly subjected to the formation of PDA coating on the biomaterial interface caused by the oxidation reaction of dopamine (DA) in weak alkaline solution.”

Nucleophilic agents containing amino, thiol, imidazole, or mercapto groups can attack catechol or diketone groups exposed on the polydopamine layer via Schiff-base and Michael addition reactions, thereby providing improved surface properties to biosubstitutes.

“Nucleophilic agents containing functional groups such as amino, thiol, imidazole, and mercapto can readily attack the catechol or diketone groups exposed on the PDA layer via Shiff-base and Michael addition reactions so that to provide improved surface properties to the biosubstitutes [29, 55, 56].”

Several mechanisms of the PDA coating layer have been developed and they all consist essentially of two steps, including the autooxidation and intramolecular rearrangement of DA monomers and polymerization of DA monomers.

“Several mechanisms of the PDA coating layer have been developed and they all consist essentially of two steps as shown in Figure 1, including the autooxidation and intramolecular rearrangement of DA monomers and polymerization of DA monomers [29, 31, 38].”

The first model exhibits a "covalent bonding" polymerization fashion where DA is polymerized via 5,6-dihydroxyindole monomers following further oxidization and subsequent intermolecular cross-linking of PDA.

“The first model exhibits a “covalent bonding” polymerization fashion where DA is polymerized via 5,6-dihydroxyindole monomers following further oxidization and subsequent intermolecular cross-linking of PDA [29, 40–44].”

On organic material surfaces, oxidation of catechol groups exposed on the polydopamine coating layer forms quinone/semiquinone, leading to irreversible covalent bonding between biomolecules and the organic material surface via Michael addition and Schiff formation reactions, and further triggering intermolecular cross-linking among polydopamine polymers.

“For the surface of organic material, the oxidation of catechol group exposed on the PDA coating layer results in the formation of quinone/semiquinone to form irreversible covalent bonding [19] between biomolecules and the surface of organic material via similar Michael addition and Schiff formation reactions [29] and thereby further trigger the intermolecular cross-linking reactions among PDA”

Marine mussels secrete proteinaceous glues to tightly adhere to wet rock surfaces.

“In nature, marine mussels secrete proteinaceous glues to tightly adhere to wet rock surfaces [1].”

Upon oxidative polymerization of dopamine, a polydopamine coating layer can form on various substrate interfaces, including noble metals, oxides, ceramics, polymers, and semiconductors.

“Upon the occurrence of oxidative polymerization of DA, PDA coating layer can be perfectly formed on various interfaces of substrates including noble metals, oxides, ceramics, polymers, and semiconductors [29].”

Polydopamine exhibits inherent antibacterial and antibiofilm activities.

“Polydopamine exhibits inherent antibacterial and antibiofilm activities.”

In ISO 10993-5 extract testing, co-culture of human gingival fibroblasts with PDA nanoparticles at 0.5 mg mL−1 for 72 h resulted in cell viabilities exceeding 92% by MTT assays.

“According to standard ISO 10993–5 extract testing, co-culture of human gingival fibroblasts with PDA nanoparticles at a concentration of 0.5 mg mL−1 for 72 h resulted in cell viabilities exceeding 92% as determined by MTT assays.”

Immunohistochemical analysis showed that the expression of inflammatory markers CD68 and CD3 peaked at approximately 2 weeks and subsequently declined, while the macrophage M1/M2 ratio decreased from 2.1 to 0.6.

“Immunohistochemical analysis showed that the expression of inflammatory markers CD68 and CD3 peaked at approximately 2 weeks and subsequently declined, while the macrophage M1/M2 ratio decreased from 2.1 to 0.6.”

Data from a New Zealand rabbit tibial implantation model demonstrated favorable host responses to PDA-modified titanium alloy screws.

“With respect to in vivo tissue compatibility, data from a New Zealand rabbit tibial implantation model demonstrated favorable host responses to PDA-modified titanium alloy screws.”

Live/Dead fluorescence confocal imaging revealed intact cell membranes and normal nuclear morphology, with no evidence of membrane disruption or nuclear condensation.

“Live/Dead fluorescence confocal imaging further revealed intact cell membranes and normal nuclear morphology, with no evidence of membrane disruption or nuclear condensation.”

Histological analysis at 4, 12, and 26 weeks post-implantation revealed only mild, localized mononuclear cell infiltration on hematoxylin and eosin staining, without the formation of thick fibrous capsules (<50 μm).

“Histological analysis at 4, 12, and 26 weeks post-implantation revealed only mild, localized mononuclear cell infiltration on hematoxylin and eosin staining, without the formation of thick fibrous capsules (<50 µm).”

The proportion of cells positive for the early apoptosis marker Annexin V remained below 3%, with no statistically significant difference relative to the negative control.

“In parallel, the proportion of cells positive for the early apoptosis marker Annexin V remained below 3%, with no statistically significant difference relative to the negative control.”

In periodontal ligament stem cells, PDA surface coatings were associated with a 1.8-fold increase in focal adhesion kinase phosphorylation.

“Notably, in periodontal ligament stem cells, PDA surface coatings were associated with a 1.8-fold increase in focal adhesion kinase phosphorylation, suggesting that PDA is not only non-cytotoxic but may actively promote cell adhesion and spreading.”