Frank Rupp

A Review on the Wettability of Dental Implant Surfaces II: Biological and Clinical Aspects

Dental and orthopedic implants have been under continuous advancement to improve their interactions with bone and ensure a successful outcome for patients. Surface characteristics such as surface topography and surface chemistry can serve as design tools to enhance the biological response around the implant, with in vitro, in vivo and clinical studies confirming their effects. However, the comprehensive design of implants to promote early and long-term osseointegration requires a better understanding of the role of surface wettability and the mechanisms by which it affects the surrounding biological environment. This review provides a general overview of the available information about the contact angle values of experimental and of marketed implant surfaces, some of the techniques used to modify surface wettability of implants, and results from in vitro and clinical studies. We aim to expand the current understanding on the role of wettability of metallic implants at their interface with blood and the biological milieu, as well as with bacteria, and hard and soft tissues.

Potential of chemically modified hydrophilic surface characteristics to support tissue integration of titanium dental implants

In the past, several modifications of specific surface properties such as topography, structure, chemistry, surface charge, and wettability have been investigated to predictably improve the osseointegration of titanium implants. The aim of the present review was to evaluate, based on the currently available evidence, the impact of hydrophilic surface modifications of titanium for dental implants. A surface treatment was performed to produce hydroxylated/hydrated titanium surfaces with identical microstructure to either acid-etched, or sand-blasted, large grit and acid-etched substrates, but with hydrophilic character. Preliminary in vitro studies have indicated that the specific properties noted for hydrophilic titanium surfaces have a significant influence on cell differentiation and growth factor production. Animal experiments have pointed out that hydrophilic surfaces improve early stages of soft tissue and hard tissue integration of either nonsubmerged or submerged titanium implants. This data was also corroborated by the results from preliminary clinical studies. In conclusion, the present review has pointed to a potential of hydrophilic surface modifications to support tissue integration of titanium dental implants.

The Roles of Titanium Surface Micro/Nanotopography and Wettability on the Differential Response of Human Osteoblast Lineage Cells

Surface micro- and nanostructural modifications of dental and orthopedic implants have shown promising in vitro, in vivo and clinical results. Surface wettability has also been suggested to play an important role in osteoblast differentiation and osseointegration. However, the available techniques to measure surface wettability are not reliable on clinically relevant, rough surfaces. Furthermore, how the differentiation state of osteoblast lineage cells impacts their response to micro/nanostructured surfaces, and the role of wettability on this response, remain unclear. In the current study, surface wettability analyses (optical sessile drop analysis, environmental scanning electron microscopic analysis and the Wilhelmy technique) indicated hydrophobic static responses for deposited water droplets on microrough and micro/nanostructured specimens, while hydrophilic responses were observed with dynamic analyses of micro/nanostructured specimens. The maturation and local factor production of human immature osteoblast-like MG63 cells was synergistically influenced by nanostructures superimposed onto microrough titanium (Ti) surfaces. In contrast, human mesenchymal stem cells cultured on micro/nanostructured surfaces in the absence of exogenous soluble factors exhibited less robust osteoblastic differentiation and local factor production compared to cultures on unmodified microroughened Ti. Our results support previous observations using Ti6Al4V surfaces showing that recognition of surface nanostructures and subsequent cell response is dependent on the differentiation state of osteoblast lineage cells. The results also indicate that this effect may be partly modulated by surface wettability. These findings support the conclusion that the successful osseointegration of an implant depends on contributions from osteoblast lineage cells at different stages of osteoblast commitment.

A review on the wettability of dental implant surfaces I: Theoretical and experimental aspects

The surface wettability of biomaterials determines the biological cascade of events at the biomaterial/host interface. Wettability is modulated by surface characteristics, such as surface chemistry and surface topography. However, the design of current implant surfaces focuses mainly on specific micro- and nanotopographical features, and is still far from predicting the concomitant wetting behavior. There is an increasing interest in understanding the wetting mechanisms of implant surfaces and the role of wettability in the biological response at the implant/bone or implant/soft tissue interface. Fundamental knowledge related to the influence of surface roughness (i.e. a quantification of surface topography) on titanium and titanium alloy surface wettability, and the different associated wetting regimes, can improve our understanding of the role of wettability of rough implant surfaces on the biological outcome. Such an approach has been applied to biomaterial surfaces only in a limited way. Focusing on titanium dental and orthopaedic implants, the present study reviews the current knowledge on the wettability of biomaterial surfaces, encompassing basic and applied aspects that include measurement techniques, thermodynamic aspects of wetting and models predicting topographical and roughness effects on the wetting behavior.

Comparison of different in vitro tests for biocompatibility screening of Mg alloys.

Standard cell culture tests according to ISO 10993 have only limited value for the biocompatibility screening of degradable biomaterials such as Mg alloys. The correlation between in vitro and in vivo results is poor. Standard cytotoxicity tests mimic the clinical situation to only a limited extent, since in vivo proteins and macromolecules in the blood and interstitial liquid will influence the corrosion behaviour and, hence, biocompatibility of Mg alloys to a significant extent. We therefore developed a modified cytotoxicity test simulating the in vivo conditions by use of bovine serum as the extraction vehicle instead of the cell culture medium routinely used in standard cytotoxicity testing according to ISO 10993-5. The modified extraction test was applied to eight experimental Mg alloys. Cytotoxicity was assayed by inhibition of cell metabolic activity (XTT test). When extraction of the alloy samples was performed in serum instead of cell culture medium the metabolic activity was significantly less inhibited for six of the eight alloys. The reduction in apparent cytotoxicity under serum extraction conditions was most pronounced for MgZn1 (109% relative metabolic activity with serum extracts vs. 26% in Dulbeccos modified Eagles medium (DMEM)), for MgY4 (103% in serum vs. 32% in DMEM) and for MgAl3Zn1 (84% vs. 17%), resulting in a completely different cytotoxicity ranking of the tested materials when serum extraction was used. We suppose that this test system has the potential to enhance the predictability of in vivo corrosion behaviour and biocompatibility of Mg-based materials for biodegradable medical devices.

Effect of Heterogenic Surfaces on Contact Angle Hysteresis: Dynamic Contact Angle Analysis in Material Sciences

Recently, the author successfully applied the classic Wilhelmy balance method and the dynamic contact angle analysis (DCA) on initial interfacial reactions of surface-modified biomaterials. In this study, the authors present further results which underline the potential of these methods to yield time-resolved data of ionic and protein interfacial reactions. In contrast to many spectroscopic methods, an on-line method, which works time-resolved and without disturbing the interface, would be important in the process-engineered quality control. This is underlined by the fact, that many biomedical material surfaces currently are pre-biofunctionalized before their application in order to increase their biocompatibility and bifunctionality. The above-outlined statement of the problems involves many disciplines. In this approach, it is highlighted and discussed on the background of current research on biomaterials.

Surface-immobilized PAMAM-dendrimers modified with cationic or anionic terminal functions: Physicochemical surface properties and conformational changes after application of liquid interface stress

Functionalization of surfaces with highly branched dendrimer molecules has gained attractiveness for various applications because the number of functional groups exceeds those of surfaces functionalized with self-assembled monolayers. So far, little is known about the physicochemical properties of dendrimer functionalized surfaces, especially if the flexibility of dendrimer structure remains after covalent immobilization. Therefore, the purpose of this study was to covalently immobilize polyamidoamine (PAMAM) dendrimer molecules exhibiting terminal amine and carboxyl groups to silicon model surfaces and to explore their properties and structure at the solid-air and solid-liquid interface. Our results show that the surface free energy is higher for PAMAM coatings than for analogously terminated SAMs and also higher for carboxyl than amine functionalized coatings. Furthermore, several findings suggest that conformational freedom of the dendrimers was preserved after surface immobilization. Wet compared to dry PAMAMNH(2) surfaces show reduced hydrophilicity and increased contact angle hysteresis, whereas PAMAMCOOH surfaces become more hydrophilic and showed decreased hysteresis. Streaming current measurements showed an unexpected behavior for PAMAMCOOH surfaces in that they reveal a net positive surface charge over a wide pH range in spite of the carboxylated periphery. All of these results indicate a certain degree of masking, burrowing, back-folding and unfolding of functional groups upon environmental changes.

UV-A and UV-C light induced hydrophilization of dental implants.

OBJECTIVES Wettability is increasingly considered to be an important factor determining biological responses to implant materials. In this context, the purpose of this study was to compare the dynamic wettability of dental implants made from different bulk materials and modified by different surface modifications, and to analyze the respective changes of wettability upon irradiating these implants by UV-A or UV-C light. METHODS Four original screw-type implants were investigated: One grit-blasted/acid-etched and one anodically oxidized titanium, one zirconia and one polyetheretherketone implant. Additionally, experimental, screwless, machined titanium cylinders were included in the study. Part of that cylinders and of blasted/etched implants were further modified by a magnetron-sputtered photocatalytic anatase thin film. Scanning electron microscopy was used to investigate the surface micro- and nanostructures. Samples were treated by UV-A (382nm, 25mWcm(-2)) and UV-C (260nm, 15mWcm(-2)) for entire 40min, respectively, and their wettability was quantified by dynamic contact angle (CA) analysis from multi-loop Wilhelmy experiments. RESULTS All implants are characterized by submicron- and nanosized surface features. Unexposed implants were hydrophobic (CA>90°). Upon UV-A, solely the implants with anatase coating became superhydrophilic (CA<5°). Upon UV-C, the blasted/etched implants turned superhydrophilic, the anodized titanium and the zirconia implants were considerably (CA=34° and 27°, respectively) and the PEEK implants slightly (CA=79°) hydrophilized. SIGNIFICANCE The wettability of implant surfaces can be improved by UV irradiation. The efficiency of UV-A and UV-C irradiation to lower the CA by photocatalysis or photolysis, however, is strongly dependent on the specific material and surface. Thus, attempts to photofunctionalize these surfaces by irradiation is expected to result in a different pattern of bioresponses.

Bacterial interactions with proteins and cells relevant to the development of life-threatening endocarditis studied by use of a quartz-crystal microbalance

Implant-related infections are a major challenge in clinical routine because of severe complications, for example infective endocarditis (IE). The purpose of this study was to investigate the real-time interaction of S. gordonii with proteins and cells important in the development of IE, in a flow system, by use of a quartz-crystal microbalance (QCM). Acoustic sensors were biologically modified by preconditioning with sterile saliva, platelet-poor plasma (PPP), or platelet-rich plasma (PRP), followed then by perfusion of a bacterial suspension. After perfusion, additional fluorescence and scanning electron microscopic (SEM) studies were performed. The surface structure of S. gordonii was analyzed by atomic force microscopy (AFM). Compared with S. gordonii adhesion on the abiotic sensor surface following normal mass loading indicated by a frequency decrease, adhesion on saliva, PPP, or PRP-conditioned sensors resulted in an increase in frequency. Furthermore, adhesion induced slightly increased damping signals for saliva and PPP-coated sensors but a decrease upon bacterial adhesion to PRP, indicating the formation of a more rigid biofilm. Microscopic analysis confirmed the formation of dense and vital bacterial layers and the aggregation of platelets and bacteria. In conclusion, our study shows that the complex patterns of QCM output data observed are strongly dependent on the biological substrate and adhesion mechanisms of S. gordonii. Overall, QCM sheds new light on the pathways of such severe infections as IE.

Comparative evaluation of topographical data of dental implant surfaces applying optical interferometry and scanning electron microscopy

OBJECTIVE Comparability of topographical data of implant surfaces in literature is low and their clinical relevance often equivocal. The aim of this study was to investigate the ability of scanning electron microscopy and optical interferometry to assess statistically similar 3-dimensional roughness parameter results and to evaluate these data based on predefined criteria regarded relevant for a favorable biological response. METHODS Four different commercial dental screw-type implants (NanoTite Certain Prevail, TiUnite Brånemark Mk III, XiVE S Plus and SLA Standard Plus) were analyzed by stereo scanning electron microscopy and white light interferometry. Surface height, spatial and hybrid roughness parameters (Sa, Sz, Ssk, Sku, Sal, Str, Sdr) were assessed from raw and filtered data (Gaussian 50μm and 5μm cut-off-filters), respectively. Data were statistically compared by one-way ANOVA and Tukey-Kramer post-hoc test. For a clinically relevant interpretation, a categorizing evaluation approach was used based on predefined threshold criteria for each roughness parameter. RESULTS The two methods exhibited predominantly statistical differences. Dependent on roughness parameters and filter settings, both methods showed variations in rankings of the implant surfaces and differed in their ability to discriminate the different topographies. Overall, the analyses revealed scale-dependent roughness data. Compared to the pure statistical approach, the categorizing evaluation resulted in much more similarities between the two methods. SIGNIFICANCE This study suggests to reconsider current approaches for the topographical evaluation of implant surfaces and to further seek after proper experimental settings. Furthermore, the specific role of different roughness parameters for the bioresponse has to be studied in detail in order to better define clinically relevant, scale-dependent and parameter-specific thresholds and ranges.