Surface modification strategies to reinforce the soft tissue seal at transmucosal region of dental implants

Abstract

Soft tissue seal around the transmucosal region of dental implants is crucial for shielding oral bacterial invasion and guaranteeing the long-term functioning of implants. Compared with the robust periodontal tissue barrier around a natural tooth, the peri-implant mucosa presents a lower bonding efficiency to the transmucosal region of dental implants, due to physiological structural differences. As such, the weaker soft tissue seal around the transmucosal region can be easily broken by oral pathogens, which may stimulate serious inflammatory responses and lead to the development of peri-implant mucositis. Without timely treatment, the curable peri-implant mucositis would evolve into irreversible peri-implantitis, finally causing the failure of implantation. Herein, this review has summarized current surface modification strategies for the transmucosal region of dental implants with improved soft tissue bonding capacities (e.g., improving surface wettability, fabricating micro/nano topographies, altering the surface chemical composition and constructing bioactive coatings). Furthermore, the surfaces with advanced soft tissue bonding abilities can be incorporated with antibacterial properties to prevent infections, and/or with immunomodulatory designs to facilitate the establishment of soft tissue seal. Finally, we proposed future research orientations for developing multifunctional surfaces, thus establishing a firm soft tissue seal at the transmucosal region and achieving the long-term predictability of dental implants.

Keywords: Antibacterial; Dental implant transmucosal region; Immunomodulation; Soft tissue seal; Surface modifications.

Graphical abstract

Fig. 1

Illustration showing the biological width around a natural toot and the soft tissue seal around a dental implant. (a) The attaching structures of periodontal biological width, which exhibits good defensive ability against bacterial invasion. (b) The attaching structures of peri-implant soft tissue seal, which exhibits inferior defensive ability against bacterial invasion.

Fig. 2

Illustration showing the structures of hemidesmosome and focal adhesion. (a) A transmission electron microscope image of a hemidesmosome. (b) A schematic drawing of the hemidesmosome. Adapted with permission from Ref. [35]. Copyright 2006 Elsevier Ltd. (c) The organization of green fluorescent protein (GFP)-paxillin-labeled focal adhesions (green) and phalloidin-labeled filamentous actin (red), on rigid (upper panel) or soft (lower panel) surfaces. Adapted with permission from Ref. [39]. Copyright 1969 Springer Nature Limited. (d) A schematic representation of the formation of focal adhesion. Adapted with permission from Ref. [36]. Copyright 2021 Elsevier B.V.

Fig. 3

The temporal sequence involved in the wound healing of peri-implant mucosa. The biological events occur after the implantation include bleeding, clotting, inflammation, cell proliferation, collagen deposition, and final tissue maturation. ECM extracellular matrix.

Fig. 4

Illustration showing the surface modification strategies to reinforce the soft tissue seal at transmucosal region of dental implants based on the three rationales: promoting soft tissue attachment, eliminating bacterial colonization, and regulating immune microenvironment. ECM extracellular matrix, PAR4-AP protease activated receptor 4-activating peptide, CLA conjugated linoleic acid, modSLA modified sandblasted, large-grit, acid-etched technique, IL-23 interleukin 23, CeO₂ ceria, PDGF-B platelet-derived growth factor subunit B.

Fig. 5

Illustration showing the surface modification strategies to promote soft tissue attachment, which mainly include improving surface wettability, manipulating surface topography, altering surface chemical composition, and constructing biomimetic coatings. UV ultraviolet, Li lithium, Mg magnesium, Zn zinc, Ta tantalum, Ca calcium, ECM extracellular matrix.

Fig. 6

Illustration showing that NTP treatment could drastically increase surface wettability, leading to improved epithelial sealing and connective tissue attachment. (a) Photographs of Ti disk (Control) and non-thermal plasma-treated Ti disk (NTP). (b) Scanning electron microscopy images of the surfaces. (c) Water contact angles of the surfaces. (d) H&E staining of peri-implant mucosa. Black arrowheads indicated the lowest point of the epithelium. (e) Picrosirius Red staining of collagen in peri-implant connective tissue. (f) Immunohistochemistry of integrin α5 (indicating fibronectin-fibroblast interaction) during wound healing of peri-implant connective tissue. Adapted with permission from Ref. [72]. Copyright 2024 Atsuro Harada et al.

Fig. 7

Illustration showing the mechanisms of how Ca²⁺, Mg²⁺ and Zn²⁺ aid in the adhesion of soft tissue cells. (a) Schematic diagram showing the hypothesized mechanism of cell adhesion to the surface of Ca²⁺-modified Ti substrate. Adapted with permission from Ref. [114]. Copyright 2012 Hideyuki Okawachi et al. (b) Illustration for the possible action of Mg²⁺-modified surfaces to HGFs. Adapted with permission from Ref. [104]. Copyright 2019 Wiley Periodicals, Inc. (c) Illustration for the possible action of Mg²⁺-modified surfaces to HGFs. (d) Illustration for the possible signal pathways of the effect of Mg²⁺/Zn²⁺ on the behaviors of HGFs. Adapted with permission from Ref. [105]. Copyright 2020 Lanyu Wang et al.

Fig. 8

Illustration showing that ECM protein coatings could facilitate the adhesion of epithelial cells and fibroblasts. ECM extracellualr matrix (a) Surface modification via plasmid-mediated pLAMA3-CM gene transfection promoted the attachment of gingival epithelial cells to Ti and improved soft tissue seal at the transmucosal region. CS chitosan, COL collagen, pLAMA3-CM plasmid encoding a motif of the C-terminal globular domain of laminin α3 chain, S-Ti smooth titanium, SEM scanning electron microscope, HRP horseradish peroxidase, B new bone formation, E epithelial tissue, C connective tissue, BV blood vessel. Adapted with permission from Ref. [119]. Copyright 2019 The Royal Society of Chemistry. (b) Schematic illustration of the silanization-mediated fibronectin modification process, and confocal microscopy images of HGFs 24 h after cultivation on fibronectin modified (left panel) and pure (right panel) surfaces. Immunostaining indicated pFAK-Y397 (red) and phalloidin-staining (green) of HGFs seeded on specimens. White arrows labeled pFAK-Y397 expression at the end of actin filaments. Adapted with permission from Ref. [122]. Copyright 2021 Alena L. Palkowitz et al. (c) PDA-mediated RGD functionalization process and its effect on HGFs and bacterial adhesion for enhanced peri-implant soft tissue seal. (d) Confocal laser scanning microscopy images of HGFs on pristine zirconia (upper panel) and RGD-functionalized zirconia surfaces after 3 h (left column) and 24 h (right column) of culture. Adapted with permission from Ref. [125]. Copyright 2020 The Royal Society of Chemistry.

Fig. 9

Illustration showing the surface modification strategies balancing antibacterial effect and soft tissue attachment, which include applying antimicrobial proteins/peptides, modifying with antibacterial metallic elements, employing intrinsic bacterial agents, and developing stimuli-responsive bactericidal surfaces. Ag silver, Zn zinc, Cu copper, Ta tantalum, Ga gallium, GO graphene oxide, PDT photodynamic therapy, PTT photothermal therapy, EST electrostimulation therapy, SDT sonodynamic therapy.

Fig. 10

Illustration showing the antimicrobial activities of antimicrobial peptide, metallic element, and external stimuli-responsive platform. (a) Schematic of the synthesis of lactoferrin-derived amyloid coating on Ti (LAT). (b) Images of the bacterial colonies formed by S. aureus and P. gingivalis that adhered to the polished titanium control (PT) and LAT. (c) Antibacterial activity against S. aureus and P. gingivalis that were in contact with PT and LAT. Significant differences between PT and LAT were labeled with different letters (p < 0.01, Student's t-test, n = 6) (d) SEM images of S. aureus and P. gingivalis grown on the surfaces of PT and LAT. Adapted with permission from Ref. [131]. Copyright 2023 Wiley-VCH GmbH. (e) The preparation of AgNPs-loaded chitosan-hepatin polyelectrolyte multilayers (PEMs) on Ti substrate. (f) SEM images of P. gingivalis on Ti (left) and PEMs (right) samples. Adapted with permission from Ref. [129]. Copyright 2019 Springer Science Business Media, LLC. (g) Nanoporous Ti implants toward electrical stimulation therapy (EST). Schematic representation: (left to right) anodization of Ti implants to fabricate TiO₂ nanopores (NPs) and magnesiothermic reduction to convert TiO₂-NP to Ti-NP; and EST using nanopores toward soft-tissue integration and antibacterial efficacy. (h) Live/Dead staining of biofilms on Ti and EST-applied Ti-NP surfaces. EST parameters: 1.5 V for 5 min per day. Adapted with permission from Ref. [100]. Copyright 2024 Karan Gulati et al.

Fig. 11

Illustration showing the surface modification strategies based on immunomodulation to facilitate soft tissue seal, which include accelerating blood coagulation, and attenuating inflammation to create a repair-supportive immune microenvironment. PAR4-AP protease activated receptor 4-activating peptide, PDGF-B platelet-derived growth factor subunit B, TNF-α tumor necrosis factor α, IL-1β interleukin 1β, TGF-β transforming growth factor β, IL-10 interleukin 10, modSLA modified sandblasted, large-grit, acid-etched technique, IL-4 interleukin 4, CCN2 cellular communication network factor 2, IL-23 interleukin 23, iNOS inducible nitric oxide synthase, CLA conjugated linoleic acid, CO carbon monoxide, CeO₂ ceria, Fe-NC iron-nitrogen-doped carbon single-atom.

Fig. 12

Illustration showing the immunomodulatory activities of coagulation-related agent, growth factor, and nanozyme. (a) Atomic force microscope (AFM) topography image of an aligned platelet lysate (PL) sample on the border of the cellulose nanocrystals (CNC)-coated titanium surface. The arrow indicated the approximate local radial axis on that part of the surface. (b) Directionality histogram of CNC orientation at both center and border of the aligned surfaces. (c) Proteomic analysis of the PL proteins adsorbed on CNC surface. Proteins organized according to their protein class. Categories with a representation lower than 1 % were grouped in “other,” The percentage (%) corresponds to the fraction of protein hits in a category against the total number of process hits. (d) Macrophages incubated on titanium (Ti), CNC-coated Ti (Ti/CNC) surface, or CNC-coated PL aligned Ti (Ti/CNC/PL) surface were immunostained with anti-CCR7 (M1-like) or anti-CD206 (M2-like), which appeared in green, while nuclei and cytoskeleton appeared in blue and red, respectively. Adapted with permission from Ref. [130]. Copyright 2021 Wiley-VCH GmbH. (e)Schematic diagram of preparing a CCN2 bearing mesoporous silica nanoparticles (MSNs) on micro-arc oxidated (MAO) titanium substrates (CCN2@MSNs-Ti) to enhance peri-implant soft tissue seal. CCN2 cellular communication network factor 2 (f) Comparison of soft tissue around implants in Ti and CCN2@MSNs-Ti groups of rats at 4 w post implantation. (g) SEM images of the interfaces between the soft tissue and implant surface. The shapeless and rough Ti oxide layers formed by MAO treatment were visible on the surfaces of CCN2@MSNs-Ti implants, which were shown by a red dashed curve. (h) Van Gieson staining images of the rat tibias, wherein soft tissue was stained purple and new bone formation was stained red. The yellow dashed curve outlined the extent of epithelial downgrowth. I implant, S soft tissue, B bone. (i) Relative mRNA expression levels of inflammation-related factors (TNF-α and IL-1β). Data were presented as mean ± S.D. (n = 3, *p < 0.05, **p < 0.01, ****p < 0.0001). Adapted with permission from Ref. [221]. Copyright 2023 American Chemical Society. (j) Schematic showing the construction of nanoceria-coated Ti disks (Ti@Ce). (k) Intracellular ROS levels in HGFs as indicated by green signals under 500 μM H₂O₂ exposure. (l ∼ o) Heat map showing DEGs in Ti@Ce_500 μM, Ti_500 μM, Ti_0 μM, and Ti@Ce_0 μM from specific GO terms related to cell adhesion, antioxidant activity, apoptosis process, and cellular response to FGF stimulus. HGFs human gingival fibroblasts, FGF fibroblast growth factor. Adapted with permission from Ref. [239]. Copyright 2024 American Chemical Society.

Fig. 13

Illustration showing the future perspectives for enhancing peri-implant soft tissue seal, where constructing bioinspired surfaces, hybrid surfaces, multifunctional surfaces, and intelligent surfaces could be considered. OEpSCs odontogenic epithelial stem cells, DFCs dental follicle cells, ROS reactive oxygen species.