Mussel-Inspired Polydopamine-Based Multilayered Coatings for Enhanced Bone Formation

Abstract

Repairing bone defects remains a challenge in clinical practice and the application of artificial scaffolds can enhance local bone formation, but the function of unmodified scaffolds is limited. Considering different application scenarios, the scaffolds should be multifunctionalized to meet specific demands. Inspired by the superior adhesive property of mussels, polydopamine (PDA) has attracted extensive attention due to its universal capacity to assemble on all biomaterials and promote further adsorption of multiple external components to form PDA-based multilayered coatings with multifunctional property, which can induce synergistic enhancement of new bone formation, such as immunomodulation, angiogenesis, antibiosis and antitumor property. This review will summarize mussel-inspired PDA-based multilayered coatings for enhanced bone formation, including formation mechanism and biofunction of PDA coating, as well as different functional components. The synergistic enhancement of multiple functions for better bone formation will also be discussed. This review will inspire the design and fabrication of PDA-based multilayered coatings for different application scenarios and promote deeper understanding of their effect on bone formation, but more efforts should be made to achieve clinical translation. On this basis, we present a critical conclusion, and forecast the prospects of PDA-based multilayered coatings for bone regeneration.

Keywords: bone regeneration; immunomodulation; multifunction; multilayered coating; osteogenesis; polydopamine.

FIGURE 1

The formation of PDA coatings onto plenty of materials’ surfaces. (A) Photograph of a mussel attached to PTFE. (B,C) Interfacial location of Mefp-5, as well as the representation of catechol and amine groups. (D) The sequence of amino acid in Mefp-5. (E) DA contains same functional catechol and amine groups. (F) A schematic illustration of PDA deposition. (G) Thickness of PDA coating. (H) XPS evaluation of PDA-coated surfaces (Lee et al., 2007). Copyright 2007, The American Association for the Advancement of Science.

FIGURE 2

Graphical diagram for fabrication of PDA-based multilayered coatings to achieve multi-functionalization and enhanced bone formation. (Created with BioRender.com).

FIGURE 3

Schematic illustration for synthesis of PDA via two pathways: (A) covalent oxidative polymerization and (B) physical self-assembly pathways (Hong et al., 2012). Copyright 2012, Wiley-VCH.

FIGURE 4

Changes of surface physiochemical property after PDA modification on different biomaterials. Changes of surface morphology observed by (A) SEM and (D) AFM images; (B) Changes of surface wettability; Changes of chemical conponents detected by (C) Raman spectra and (E) XPS analysis, the characteristic peaks of PDA can be observed (Wang H. et al., 2019). Copyright 2019, American Chemical Society.

FIGURE 5

After PDA modification and Ag decoration, changes of chemical components on HA substrates are detected by (A) FTIR, and the characteristic peaks are identified. The characteristic peaks of PDA (1602 cm^-1 and 1515 cm^-1) can be observed. Changes of crystalline structures are detected by (B) XRD analysis, and the crystalline structures stay unchanged after PDA modification, where the quadrangles represent peaks of Ag and the pentagrams represent peaks of HA. (Zhang et al., 2021). Copyright 2021, Elsevier.

FIGURE 6

The osteogenic activity and mechanism of PDA-coated Ti, PEEK and HA substrates. (A) The enhancement of cell proliferation and osteogenic differentiation of BMSCs on PDA-coated substrates. (B) The enhanced osseointegration of PDA-modified PEEK implants via histomorphometry analysis. (C) Western blot experiments and quantitative analysis of the expression of FAK, p-FAK, and MAPK signaling pathways proteins of BMSCs after culturing for 48 h. (D) Schematic diagram for the mechanism of enhanced osteogenic differentiation and osseointegration of PDA coating. (*p < 0.05) (Wang H. et al., 2019). Copyright 2019, American Chemical Society.

FIGURE 7

Recruitment of BMSCs induced by E7-loaded PDA-modified silk membrane. (A) Schematic illustration of the PDA-modified silk fibroin and PDA-mediated E7 peptide; (B) CD44 immunofluorescent staining of the in vitro recruited BMSCs after 3 days; (C) CD44 immunofluorescent staining of the in vivo recruited BMSCs after 7 days. Blue arrow: the BMSCs grew into the scaffolds (Wu et al., 2019). Copyright 2019, American Chemical Society.

FIGURE 8

Schematic illustration for the effect of immunomodulation on osteogenesis via the PDA-based peptide-loaded coating. The peptide binds steadily to the Ti implant with the assistance of PDA. Under the LPS-induced inflammatory conditions, the biomimetic osteogenic peptide coating exhibited antiinflammatory property and changed the macrophages to the M2 phenotype, which in turn enhanced new bone formation (Bai et al., 2020). Copyright 2020, Elsevier.

FIGURE 9

Blood vessel formation of different PEEK samples. (A) Pictures of HUVECs angiogenesis assay and vivo CAM assay; the number of intersections of the neovessel network: (B) HUVECs and (C) CAM; *p < 0.05, **p < 0.01, and ***p < 0.001 (Xiao et al., 2021). Copyright 2021, American Chemical Society.

FIGURE 10

PDA-based PP-pDA-Ag-COL scaffold for antibacterial and osteogenic activity. (A) Schematic illustration of the preparation procedure. (B) DAPI immunofluorescent staining of bacterial attachment. (C) 3D reconstruction and H&E staining of the regenerated periodontal tissues in periodontitis mouse model 6 weeks after implantation (Qian et al., 2019). Copyright 2019, American Chemical Society.

FIGURE 11

The PDA-based multilayered coating with multiple functions for tumor suppression and osteogenesis. (A) Schematic illustration of the coating fabrication. (B) Photothermal heating curves of different samples. (C) Live/Dead fluorescent staining of tumor cells. (D) In vivo evaluation of osteogenic activity. **p < 0.05 and **p < 0.01 (Yin et al., 2020). Copyright 2020, American chemical society.