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Successful dental implant therapy not only relies on osseointegration but also on the health and stability of the surrounding soft tissues. Soft tissue concerns are critical to the long-term success of dental implants, influencing both function and appearance. This review looks at soft tissue integration with dental implants from both microscopic and macroscopic viewpoints. It investigates the biological mechanisms, therapeutic management, and factors that influence soft tissue health around implants. By exploring these issues, the review hopes to provide a full understanding of the importance of soft tissue considerations in dental implantology.

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Soft tissue integration around titanium (Ti) implants is weaker than that around natural teeth, compromising long-term success of Ti implants. Carbon monoxide (CO) possesses distinctive therapeutic properties, rendering it as a highly promising candidate for enhancing STI. However, achieving controlled CO generation at the STI interface remains challenging. Herein, a controlled CO-releasing dual-function coating was constructed on Ti surfaces. Under near-infrared (NIR) irradiation, the designed surface could actively accelerate CO generation for antibiosis against both aerobic and anaerobic bacteria. More importantly, in the absence of NIR, the slow release of CO induces macrophage polarization from pro-inflammatory phenotype towards pro-regenerative phenotype. In a rat implantation model with induced infection, the designed surface effectively controlled the bacterial infection, alleviates accompanying inflammation and modulated immune microenvironment, leading to enhanced STI. Single-cell sequencing revealed that the coating alters the cytokine profile within the soft tissue, thereby influencing cellular functions. Differentially expressed genes in macrophages are highly enriched in the PIK3-Akt pathway. Furthermore, the cellular communication between fibroblasts and macrophages was significantly enhanced through the CXCL12/CXCL14/CXCR4 and CSF1-CSF1R ligand-receptor pair. These findings indicate that our coating showed an appealing prospect for enhancing STI around Ti implants, which would ultimately contribute to the improved long-term success of Ti implants.

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AIMS: To test whether titanium surface roughness disparity might be used to specifically guide the behavior of gingiva fibroblasts and keratinocytes, thereby improving the quality of soft tissue (ST) integration around abutments. METHODS: Titanium discs resembling the roughness of enamel (M) or cementum (MA) were created with normal or increased hydrophilicity and used as substrates for human fibroblasts and keratinocytes. Adhesion and proliferation assays were performed to assess cell-type specific responses upon encountering the different surfaces. Additionally, immunofluorescence and qPCR analyses were performed to study more in depth the behavior of fibroblasts and keratinocytes on MA and M surfaces, respectively. RESULTS: While enamel-like M surfaces supported adhesion, growth and a normal differentiation potential of keratinocytes, cementum-emulating MA surfaces specifically impaired the growth of keratinocytes. Vice versa, MA surfaces sustained regular adhesion and proliferation of fibroblasts. Yet, a more intimate adhesion between fibroblasts and titanium was achieved by an increased hydrophilicity of MA surfaces, which was associated with an increased expression of elastin. CONCLUSION: The optimal titanium implant abutment might be achieved by a bimodal roughness design, mimicking the roughness of enamel (M) and cementum with increased hydrophilicity (hMA), respectively. These surfaces can selectively elicit cell responses favoring proper ST barrier by impairing epithelial downgrowth and promoting firm adhesion of fibroblasts.

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Achieving robust soft tissue integration around dental implants is crucial for long-term clinical success, as it forms a protective biological seal against bacterial invasion. However, the soft tissue attachment to implants is relatively deficient compared to natural teeth, particularly in the connective tissue region lacking sufficient gingival fibroblasts and collagen fiber alignment. This study proposed an innovative strategy to enhance peri­implant soft tissue integration by modulating gingival fibroblast behavior via photothermal conversion. Zirconia surfaces were coated with polydopamine (PDA), a melanin-like polymer exhibiting near-infrared (NIR) absorption for photothermal conversion. Under NIR irradiation, the PDA coating enabled mild hyperthermia (42-43 °C) on the zirconia surface. Remarkably, this mild photothermal stimulation significantly promoted human gingival fibroblast proliferation, adhesion, and collagen production compared to unmodified zirconia in vitro. By utilizing the photothermal properties of PDA coatings to modulate cellular behaviors beneficial for connective tissue formation, this approach provides a promising avenue to achieve improved soft tissue integration and long-term stability of dental implants. The findings highlight the innovative potential of combining biomaterial surface engineering with photothermal therapy for applications in implant dentistry.

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Dental implants have been clinically used for almost five decades with high success rates. In vitro research models used in implant dentistry are limited to two-dimensional experiments, which are reproducible and well adapted to evaluate a single parameter but do not reproduce the complexity of clinical settings. On the contrary, the in vivo research models using animals offer similar histological and anatomical features to humans, and tissue healing can be close to a clinical situation, but those models are usually accompanied with ethical concerns, and their outcomes could not be extrapolated to humans because of interspecies variabilities. This makes the development of novel in vitro models that recapitulate physiological events occurring during dental implant placement of particular interest for current research in dentistry. Also, such models could be challenged by setting a pathological environment (peri-implantitis) to better understand the disease and eventually serve as a platform to evaluate novel treatment modalities. The aim of this systematic literature review was to cover all the in vitro three-dimensional (3D) complex models available for research in implant dentistry. To accomplish this, a comprehensive search of the literature present on Scopus and PubMed databases was done using specific keywords, as well as inclusion/exclusion criteria. Out of 1334 articles found, we have finally included 27 articles in this review with publication dates between 2001 and 2022. In those articles, the 3D models were designed to study tissue-implant interface behavior in bone or gingival tissue. The articles focused on simulating implant integration, evaluating the effect of different conditions on implant integration, or developing an infection model for the implant integration process. The methods used involved implant material and cells organized in a specific 3D structure. The 3D models developed were able to simulate the process of dental implant osseo- and soft tissue integration and lead to results comparable with conventional in vitro and in vivo models. A relatively limited number of articles were obtained, which indicates that this is an emerging field, highly dependent on progresses made in biotechnologies and tissue engineering, and that further investigation is needed to enhance these 3D in vitro models.

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A holistic biointegration of percutaneous bone-anchored metallic prostheses with both hard and soft tissues dictates their longevity in the human body. While titanium (Ti) has nearly solved osseointegration, soft tissue integration of percutaneous metallic prostheses is a perennial problem. Unlike the firm soft tissue sealing in biological percutaneous structures (fingernails and teeth), foreign body response of the skin to titanium (Ti) leads to inflammation, epidermal downgrowth and inferior peri-implant soft tissue sealing. This review discusses various implant surface treatments/texturing and coatings for osseointegration, soft tissue integration, and against bacterial attachment. While surface microroughness by SLA (sandblasting with large grit and acid etched) and porous calcium phosphate (CaP) coatings improve Ti osseointegration, smooth and textured titania nanopores, nanotubes, microgrooves, and biomolecular coatings encourage soft tissue attachment. However, the inferior peri-implant soft tissue sealing compared to natural teeth can lead to peri-implantitis. Toward this end, the application of smart multifunctional bioadhesives with strong adhesion to soft tissues, mechanical resilience, durability, antibacterial, and immunomodulatory properties for soft tissue attachment to metallic prostheses is proposed.

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The design of implantable biomaterials involves precise tuning of surface features because the early cellular fate on such engineered surfaces is highly influenced by many physicochemical factors [roughness, hydrophilicity, reactive oxygen species (ROS) responsiveness, etc.]. Herein, to enhance soft tissue integration for successful implantation, Ti substrates decorated with uniform layers of nanoceria (Ce), called Ti@Ce, were optimally developed by a simple and cost-effective in situ immersion coating technique. The characterization of Ti@Ce shows a uniform Ce distribution with enhanced roughness (∼3-fold increase) and hydrophilicity (∼4-fold increase) and adopted ROS-scavenging capacity by nanoceria coating. When human gingival fibroblasts were seeded on Ti@Ce under oxidative stress conditions, Ti@Ce supported cellular adhesion, spreading, and survivability by its cellular ROS-scavenging capacity. Mechanistically, the unique nanocoating resulted in higher expression of amphiphysin (a nanotopology sensor), paxillin (a focal adhesion protein), and cell adhesive proteins (collagen-1 and fibronectin). Ti@Ce also led to global chromatin condensation by decreasing histone 3 acetylation as an early differentiation feature. Transcriptome analysis by RNA sequencing confirmed the chromatin remodeling, antiapoptosis, antioxidant, cell adhesion, and TGF-ß signaling-related gene signatures in Ti@Ce. As key fibroblast transcription (co)factors, Ti@Ce promotes serum response factor and MRTF-α nucleus localization. Considering all of this, it is proposed that the surface engineering approach using Ce could improve the biological properties of Ti implants, supporting their functioning at soft tissue interfaces and utilization as a bioactive implant for clinical conditions such as peri-implantitis.

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OBJECTIVES: Surface characteristics of implant reconstructions determine the gingival fibroblast (GF) response and thus soft tissue integration (STI). However, for monolithic implant reconstructions it is unknown whether the (hybrid) ceramic biomaterial type and its surface treatment affect GF response. Therefore, this investigation examined the influence of the implant reconstruction biomaterials hybrid ceramic (HC), lithium disilicate ceramic (LS), 4 and 5 mol% yttria partially stabilized zirconiumdioxide ceramics (4/5Y-PSZ) and their surface treatment - machining, polishing or glazing - on surface characteristics and GF response. METHODS: After characterization of surface topography and wettability by scanning electron microscopy, interferometry and contact angle measurement, the adhesion, morphology, metabolic activity and proliferation of GFs from six donors was investigated by fluorescent staining and a resazurin-based assay at days 1, 3 and 7. Titanium (Ti) served as control. RESULTS: Biomaterial type and surface treatment affected the GF response in a topography-dependent manner. Smooth polished and glazed surfaces demonstrated enhanced GF adhesion and earlier proliferation onset compared to rough machined surfaces. Due to minor differences in surface topography of polished and glazed surfaces, however, the GF response was similar for polished and glazed HC, LS, 4- and 5Y-PSZ as well as Ti. SIGNIFICANCE: Within the limits of the present investigation, polishing and glazing of machined HC, LS and 4/5Y-PSZ can be recommended to support STI-relevant cell functions in GF. Since the GF response on polished and glazed HC, LS, 4- and 5Y-PSZ surfaces and the Ti control was comparable, this investigation proofed equal cytocompatibility of these surfaces in vitro.

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To date, it is unknown whether 3D printed fixed oral implant-supported prostheses can achieve comparable soft tissue integration (STI) to clinically established subtractively manufactured counterparts. STI is mediated among others by gingival fibroblasts (GFs) and is modulated by biomaterial surface characteristics. Therefore, the aim of the present work was to investigate the GF response of a 3D printed methacrylate photopolymer and a hybrid ceramic-filled methacrylate photopolymer for fixed implant-supported prostheses in the sense of supporting an STI. Subtractively manufactured samples made from methacrylate polymer and hybrid ceramic were evaluated for comparison and samples from yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP), comprising well documented biocompatibility, served as control. Surface topography was analyzed by scanning electron microscopy and interferometry, elemental composition by energy-dispersive x-ray spectroscopy, and wettability by contact angle measurement. The response of GFs obtained from five donors was examined in terms of membrane integrity, adhesion, morphogenesis, metabolic activity, and proliferation behavior by a lactate-dehydrogenase assay, fluorescent staining, a resazurin-based assay, and DNA quantification. The results revealed all surfaces were smooth and hydrophilic. GF adhesion, metabolic activity and proliferation were impaired by 3D printed biomaterials compared to subtractively manufactured comparison surfaces and the 3Y-TZP control, whereas membrane integrity was comparable. Within the limits of the present investigation, it was concluded that subtractively manufactured surfaces are superior compared to 3D printed surfaces to support STI. For the development of biologically optimized 3D printable biomaterials, consecutive studies will focus on the improvement of cytocompatibility and the synthesis of STI-relevant extracellular matrix constituents.

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The long-term successes of implant restorations rely on both appropriate osseointegration and robust soft tissue integration (STI). Numerous studies have reported that titanium dioxide nanotube (TNT) arrays formed by electrochemical anodization (EA) can promote early osteogenesis, but the mechanical stability of such modifications is often ignored and remains underexplored. In addition, relatively little research has been done on their effects on soft tissues integration. In this study, we developed mechanically robust TNT arrays using an optimized EA system. Subsequently, we immobilized a peptide, specifically D-amino K122-4, onto the anodized TNTs via polydopamine (PDA) films to enhance their mechanical properties. Surface morphology and composition were characterized by scanning electron microscopy (SEM), atomic force microscopy, and X-ray photoelectron spectroscopy. Mechanical properties, including the elastic modulus and hardness of TNTs modified Ti surfaces, were assessed using the nano-indention test. The adhesive strength of TNTs films to the substrate was measured using the nano scratch test. Furthermore, we evaluated the adhesion, spreading, and proliferation of human gingival fibroblasts (HGFs) and periodontal pathogenic bacteria such as Streptococcus mutans (S.m) and F. nucleatum (F.n) on the surface. Results showed that the elastic modulus, hardness, and adhesive strength of anodized TNTs were significantly enhanced by the incorporation of the D-amino K122-4 peptide. Live-dead staining and SEM observation suggested a decreased surface colonization by both bacterial species. The antibacterial rate of S.m and F. n was 81.5% and 71.7%, respectively, evaluated by colony counting method. Additionally, results of CCK8 assay showed that modified TNTs slightly stimulated HGFs attachment and proliferation while producing enhanced fluorescence of integrin ß1 and F-actin, confirmed by laser confocal microscopy observation. Thus, D-amino K122-4 biofunctionalized TNTs present significantly improved mechanical properties, and the mechanically robust structures modulate HGFs proliferation and alignment, resulting in decreased bacteria growth. This novel strategy has the potential to create a surface coating for implants that exhibits superior mechanical robustness and enhanced surface-to-implant interactions.

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Soft tissue integration around the abutment of implants is the basis of long-term retention of implants. Macrophages are an important component involved in the repair of soft tissue due to their crucial role in improving the biological structure of connective tissues by regulating the fiber synthesis, adhesion, and contraction of gingival fibroblasts. Recent studies have illustrated that cerium-doped zeolitic imidazolate framework-8 (Ce@ZIF-8) nanoparticles (NPs) can attenuate periodontitis via both antibacterial and anti-inflammatory effects. However, the effect of Ce@ZIF-8 NPs on soft tissue integration around the abutment is unknown. Herein, we first prepared Ce@ZIF-8 NPs by a one-pot synthesis. Then, we probed the regulatory effect of Ce@ZIF-8 NPs on macrophage polarization, and further experiments were performed to study the changes of fiber synthesis as well as adhesion and contraction of fibroblasts in the M2 macrophage environment stimulated by Ce@ZIF-8 NPs. Strikingly, Ce@ZIF-8 NPs can be internalized by M1 macrophages through macropinocytosis and caveolae-mediated endocytosis in addition to phagocytosis. By catalyzing hydrogen peroxide to produce oxygen, the mitochondrial function was remedied, while hypoxia inducible factor-1α was restrained. Then, macrophages were shifted from the M1 to M2 phenotype via this metabolic reprogramming pathway, provoking soft tissue integration. These results provide innovative insights into facilitating soft tissue integration around implants.

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Introduction: Improving the biological sealing around dental abutments could promote the long-term success of implants. Although titanium abutments have a wide range of clinical applications, they incur esthetic risks due to their color, especially in the esthetic zone. Currently, zirconia has been applied as an esthetic alternative material for implant abutments; however, zirconia is purported to be an inert biomaterial. How to improve the biological activities of zirconia has thus become a popular research topic. In this study, we presented a novel self-glazed zirconia (SZ) surface with nanotopography fabricated by additive 3D gel deposition and investigated its soft tissue integration capability compared to that of clinically used titanium and polished conventional zirconia surfaces. Materials and Methods: Three groups of disc samples were prepared for in vitro study and the three groups of abutment samples were prepared for in vivo study. The surface topography, roughness, wettability and chemical composition of the samples were examined. Moreover, we analyzed the effect of the three groups of samples on protein adsorption and on the biological behavior of human gingival keratinocytes (HGKs) and human gingival fibroblasts (HGFs). Furthermore, we conducted an in vivo study in which the bilateral mandibular anterior teeth of rabbits were extracted and replaced with implants and corresponding abutments. Results: The surface of SZ showed a unique nanotopography with nm range roughness and a greater ability to absorb protein. The promoted expression of adhesion molecules in both HGKs and HGFs was observed on the SZ surface compared to the surfaces of Ti and PCZ, while the cell viability and proliferation of HGKs and the number of HGFs adhesion were not significant among all groups. In vivo results showed that the SZ abutment formed strong biological sealing at the abutment-soft tissue interface and exhibited markedly more hemidesmosomes when observed with a transmission electron microscope. Conclusion: These results demonstrated that the novel SZ surface with nanotopography promoted soft tissue integration, suggesting its promising application as a zirconia surface for the dental abutment.

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Soft-tissue integration (STI) plays an essential role in the long-term success of percutaneous Ti implants since it acts as a biological barrier that protects the soft and hard tissue around implants. Surface modification of Ti implants with drug-release properties to achieve soft-tissue regeneration has been proven to be effective in STI. However, the short-acting effect caused by the uncontrolled drug release of the topical delivery system limits long-term STI enhancement. Herein, a long-acting protein delivery system for Ti implants that involved micro-arc oxidation of Ti surfaces (MAO-Ti) and localized immobilization of cellular communication network factor 2 (CCN2) bearing mesoporous silica nanoparticles (MSNs) on MAO-Ti was prepared, namely, CCN2@MSNs-Ti. The CCN2 release study of CCN2@MSNs-Ti demonstrated a sustained-release profile for 21 days, which was able to maintain long-term stable STI. In addition, in vitro cell behavior evaluation results indicated that CCN2@MSNs-Ti could promote the STI-related biological response of human dermal fibroblasts via the FAK-MAPK pathway. More importantly, the system could effectively enhance STI after 4 weeks and proinflammatory factors in the soft tissue decreased significantly in a rat model of implantation. These results denote that CCN2@MSNs-Ti showed an appealing application prospect for enhanced STI around transcutaneous Ti implants, which would ultimately result in an increased success rate of percutaneous Ti implants.

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The formation of a biological seal around the neck of titanium (Ti) implants is critical for ensuring integration at the gingival site and for preventing bacterial colonization that may lead to periimplantitis. This process is guided by activated fibroblasts, named myofibroblasts, which secrete extracellular matrix (ECM) proteins and ECM-degrading enzymes resolving the wound. However, in some cases, Ti is not able to attract and activate fibroblasts to a sufficient extent, which may compromise the success of the implant. Fibronectin (FN) is an ECM component found in wounds that is able to guide soft tissue healing through the adhesion of cells and attraction of growth factors (GFs). However, clinical use of FN functionalized Ti implants is problematic because FN is difficult to obtain, and is sensitive to degradation. Herein, functionalizing Ti with a modified recombinant heparin binding II (HBII) domain of FN, mutated to include an Arg-Gly-Asp (RGD) sequence for promoting both fibroblast adhesion and GF attraction, is aimed at. The HBII-RGD domain is able to stimulate fibroblast adhesion, spreading, proliferation, migration, and activation to a greater extent than the native HBII, reaching values closer to those of full-length FN suggesting that it might induce the formation of a biological sealing.

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The difficulties associated with polyetheretherketone (PEEK) implants and soft tissue integration for craniomaxillofacial bone repair have led to a series of complications that limit the clinical benefits. In this study, 3D printed multi-stage microporous PEEK implants coated with bFGF via polydopamine were fabricated to enhance PEEK implant-soft tissue integration. Multistage microporous PEEK scaffolds prepared by sulfonation of concentrated sulfuric acid were coated with polydopamine, and then used as templates for electrophoretic deposition of bFGF bioactive factors. Achieving polydopamine and bFGF sustained release, the composite PEEK scaffolds possessed good mechanical properties, hydrophilicity, protein adhesion properties. The in vitro results indicated that bFGF/polydopamine-loaded PEEK exhibited good biocompatibility to rabbit embryonic fibroblasts (REF) by promoting cell proliferation, adhesion, and migration. Ribonucleic acid sequencing (RNA-seq) revealed that bFGF/polydopamine-loaded PEEK implants significantly upregulated the expression of genes and proteins associated with soft tissue integration and activated Wnt/ß-catenin signaling in biological processes, but related expression of genes and proteins was significantly downregulated when the Wnt/ß-catenin signaling was inhibited. Furthermore, in vivo bFGF/polydopamine-loaded PEEK implants exhibited excellent performance in improving the growth and adhesion of the surrounding soft tissue. In summary, bFGF/polydopamine-loaded PEEK implants possess soft tissue integration properties by activating the Wnt/ß-catenin signaling, which have a potential translational clinical application in the future.

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Due to their good mechanical performances and high biocompatibility, all-ceramic materials are widely applied in clinics, especially in orthopedic and dental areas. However, the "hard" property negatively affects its integration with "soft" tissue, which greatly limits its application in soft tissue-related areas. For example, dental implant all-ceramic abutments should be well integrated with the surrounding gingival soft tissue to prevent the invasion of bacteria. Mimicking the gingival soft tissue and dentine integration progress, we applied the modified ion-exchange technology to "activate" the biological capacity of lithium disilicate glass-ceramics, via introducing OH- to weaken the stability of Si-O bonds and release lithium ions to promote multi-reparative functions of gingival fibroblasts. The underlying mechanism was found to be closely related to the activation of mitochondrial activity and oxidative phosphorylation. In addition, during the ion-exchange process, the larger radius sodium ions (Na+) replaced the smaller radius lithium ions (Li+), so that the residual compressive stress was applied to the glass-ceramics surface to counteract the tensile stress, thus improving the mechanical properties. This successful case in simultaneous improvement of mechanical properties and biological activities proves the feasibility of developing "soft tissue integrative" all-ceramic materials with high mechanical properties. It proposes a new strategy to develop advanced bioactive and high strength all-ceramic materials by modified ion-exchange, which can pave the way for the extended applications of such all-ceramic materials in soft tissue-related areas.

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In reconstructive surgery using artificial materials after wide resection, soft tissues are usually adjacent to metal surfaces or mesh. The purpose of this study was to provide histological evaluation of the soft tissues adjacent to the metal surfaces of megaprostheses and mesh. Tissues from revision surgery of megaprosthesis and from wide resection after recurrent thoracic wall sarcoma were used. Histological analysis was evaluated by hematoxylin/eosin (HE) and Masson's trichrome staining, and by immunohistochemical staining for markers including cluster of differentiation 68 (CD68), vimentin, collagen type and S100A4. Soft tissue adherence to the smooth metal surface of Ti alloy was not observed. On the surface of capsule, CD68- and vimentin-positive cells formed a thin layer. In contrast, soft tissue adherence to a rough-surface cobalt chrome alloy was observed. Capsule was not apparent for this tissue, in which CD68- and vimentin-positive cells were aggregated randomly. In the resected tissues of recurrent chest wall sarcoma, muscles showed connections to connective soft tissues but did not invade to the inside of the mesh. Around the polypropylene mesh, large numbers of CD68- and vimentin-positive cells were seen. On the ePTFE, small numbers of CD68-positive cells were observed, while a larger number of the cells were vimentin positive. High accumulation of S100A4-positive cells was observed at the metal surface and polypropylene surface. Cells were strongly positive for CD68 and vimentin in tissues adjacent to metal and mesh surfaces. Macrophages and vimentin may play important roles in the foreign body reaction to metal and mesh, and so may contribute to encapsulation and fibrosis.

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Polyetheretherketone (PEEK) is a biocompatible material widely used in spinal and craniofacial implants, with potential use in percutaneous implants. However, its inertness prevents it from forming a tight seal with the surrounding soft tissue, which can lead to infections and implant failure. Conversely, the surface chemistry of percutaneous organs (i.e., teeth) helps establish a strong interaction with the epithelial cells of the contacting soft tissues, and hence a tight seal, preventing infection. The seal is created by adsorption of basement membrane (BM) proteins, secreted by epithelial cells, onto the percutaneous organ surfaces. Here, we aim to create a tight seal between PEEK and epithelial tissues by mimicking the surface chemistry of teeth. Our hypothesis is that collagen I, the most abundant tooth protein, enables integration between the epithelial tissue and teeth by promoting adsorption of BM proteins. To test this, we immobilized collagen I via EDC/NHS coupling on a carboxylated PEEK surface modified using diazonium chemistry. We used titanium alloy (Ti-6Al-4V) for comparison, as titanium is the most widely used percutaneous biomaterial. Both collagen-modified PEEK and titanium showed a larger adsorption of key BM proteins (laminin, nidogen, and fibronectin) compared to controls. Keratinocyte epithelial cell viability on collagen-modified PEEK was twice that of control PEEK and ∼1.5 times that of control titanium after 3 days of cell seeding. Both keratinocytes and fibroblasts spread more on collagen-modified PEEK and titanium compared to controls. This work introduces a versatile and biomimetic surface modification technique that may enhance PEEK-epithelial tissue sealing with the potential of extending PEEK applications to percutaneous implants, making it competitive with titanium.

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Surface topography, protein adsorption, and the loading of coating materials can affect soft tissue sealing. Graphene oxide (GO) is a promising candidate for improving material surface functionalization to facilitate soft tissue integration between cells and biomaterials. In this study, TiO2 nanotubes (TNTs) were prepared by the anodization of Ti, and TNT-graphene oxide composites (TNT-GO) were prepared by subsequent electroplating. The aim of this study was to investigate the effect of TNTs and TNT-GO surface modifications on the behavior of human gingival fibroblasts (HGFs). Commercially pure Ti and TNTs were used as the control group, and the TNT-GO surface was used as the experimental group. Scanning electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction were used to perform sample characterization. Cell adhesion, cell proliferation, cell immunofluorescence staining, a wound-healing assay, real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and Western blotting showed that the proliferation, adhesion, migration, and adhesion-related relative gene expression of HGFs on TNT-GO were significantly enhanced compared to the control groups, which may be mediated by the activation of integrin ß1 and the MAPK-Erk1/2 pathway. Our findings suggest that the biological reactivity of HGFs can be enhanced by the TNT-GO surface, thereby improving the soft tissue sealing ability.

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Titanium-based dental implants have been highly optimized to enhance osseointegration, but little attention has been given to the soft tissue-implant interface, despite being a major contributor to long term implant stability. This is strongly linked to a lack of model systems that enable the reliable evaluation of soft tissue-implant interactions. Current in vitro platforms to assess these interactions are very simplistic, thus suffering from limited biological relevance and sensitivity to varying implant surface properties. The aim of this study was to investigate how blood-implant interactions affect downstream responses of different soft tissue cells to implants in vitro, thus taking into account not only the early events of blood coagulation upon implantation, but also the multicellular nature of soft tissue. For this, three surfaces (smooth and hydrophobic; rough and hydrophobic; rough and hydrophilic with nanostructures), which reflect a wide range of implant surface properties, were used to study blood-material interactions as well as cell-material interactions in the presence and absence of blood. Rough surfaces stimulated denser fibrin network formation compared to smooth surfaces and hydrophilicity accelerated the rate of blood coagulation compared to hydrophobic surfaces. In the absence of blood, smooth surfaces supported enhanced attachment of human gingival fibroblasts and keratinocytes, but limited changes in gene expression and cytokine production were observed between surfaces. In the presence of blood, rough surfaces supported enhanced fibroblast attachment and stimulated a stronger anti-inflammatory response from macrophage-like cells than smooth surfaces, but only smooth surfaces were capable of supporting long-term keratinocyte attachment and formation of a layer of epithelial cells. These findings indicate that surface properties not only govern blood-implant interactions, but that this can in turn also significantly modulate subsequent soft tissue cell-implant interactions.