d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57

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journal homepage: www.intl.elsevierhealth.com/journals/dema

Surface characteristics of dental implants: A review

F. Rupp a,∗ , L. Liang a , J. Geis-Gerstorfer a , L. Scheideler a , F. Hüttig b

a University Hospital Tübingen, Section Medical Materials Science & Technology, Osianderstr. 2-8, 72076 Tübingen,
Germany
b Department of Prosthodontics, Centre of Dentistry, Oral Medicine, and Maxillofacial Surgery, University Hospital

Tuebingen, Osianderstr. 2-8, 72076 Tübingen, Germany

a r t i c l e i n f o a b s t r a c t

Article history: Objectives. During the last decades, several changes of paradigm have modified our view on
Received 31 July 2017 how biomaterials’ surface characteristics influence the bioresponse. After becoming aware
Accepted 15 September 2017 of the role of a certain microroughness for improved cellular contact and osseointegration of
dental titanium implants, the likewise important role of surface energy and wettability was
increasingly strengthened. Very recently, synergistic effects of nanoscaled topographical
Kewords: features and hydrophilicity at the implant/bone interface have been reported.
Endosseous dental implantation Methods. Questions arise about which surface roughness and wetting data are capable to
Roughness predict the bioresponse and, ultimately, the clinical performance. Current methods and
Wettability approaches applied for topographical, wetting and surface energetic analyses are high-
Contamination lighted. Current knowledge of possible mechanisms explaining the influence of roughness
Plasma and hydrophilicity at the biological interface is presented.
Photofunctionalisation Results. Most marketed and experimental surfaces are based on commonly available additive
Photocatalysis or subtractive surface modifying methods such as blasting, etching or anodizing. Different
Bioactivity height, spatial, hybrid and functional roughness parameters have been identified as pos-
Osseointegration sible candidates able to predict the outcome at hard and soft tissue interfaces. Likewise,
Peri-implantitis hydrophilic implants have been proven to improve the initial blood contact, to support the
wound healing and thereby accelerating the osseointegration.
Significance. There is clear relevance for the influence of topographical and wetting character-
istics on a macromolecular and cellular level at endosseous implant/biosystem interfaces.
However, we are still far away from designing sophisticated implant surfaces with the best
possible, selective functionality for each specific tissue or cavity interface. Firstly, because
our knowledge of the respective surface related reactions is at best fragmentary. Secondly,
because manufacturing of multi-scaled complex surfaces including distinct nanotopogra-
phies, wetting properties, and stable cleanliness is still a technical challenge and far away
from being reproducibly transferred to implant surfaces.
© 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

∗
Corresponding author at: University Hospital Tübingen, Section Medical Materials Science & Technology, Osianderstr. 2-8, D-72076
Tübingen, Germany.
E-mail address: frank.rupp@med.uni-tuebingen.de (F. Rupp).
https://doi.org/10.1016/j.dental.2017.09.007
0109-5641/© 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.
 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57 41

Contents
1. Functional requirements for dental implant surfaces – the concept of hybrid implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
2. From microroughness to nanoroughness and wettability – changes of paradigm at the biomaterial/bone interface . . . . . . 42
3. Measurement of surface roughness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
4. Measurement of wettability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
5. Role of cleanliness for implant surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
6. Concepts for decontamination and enhanced hydrophilicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
6.1. Prevention of contamination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
6.2. Photofunctionalisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
6.3. Plasma treatments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46
6.4. Further hydrophilization treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
7. Roughness and wettability of dental implants on the market . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
8. Implant surfaces modulate the bioresponse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
8.1. Initial implant/biosystem interactions – blood contact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
8.2. The cellular and tissue response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
8.3. Biomimetic aspects in the fields of implantology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
9. How to optimize the dental hybrid implant – what have we learnt?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .51
10. Conclusions and future perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

1. Functional requirements for dental

implant surfaces – the concept of hybrid ture, e.g., the crown. Any surface of the dental implant or, more
implants precisely, the implant system, should be optimized to fulfill
the different demands of the respective interfaces: at the hard
Dental implants are used as artificial tooth roots since more tissue interface, osteogenic properties are required to optimize
than five decades to fix and support prosthetic suprastruc- osseointegration; at the soft tissue interface, gingival attach-
tures from single crowns to fixed and removable prostheses. ment with cell-adhesive functionality for keratinocytes and
The indication ranges from single tooth gaps up to eden- fibroblasts is obligatory to ensure a tight epithelial seal that
tulism. Remarkably, since the pioneering work of Brånemark, prevents bacterial infiltration. For both interfaces, bacterial
Zarb, Albrektsson, Schulte, Schroeder and others in the field of colonization is regarded to be a main risk for severe infections
osseointegration [1–7], the material of choice is still titanium such as peri-implantitis [16] This very inflammation goes in
or titanium alloy, even though very recently alternative mate- hand with a bacterial contamination of implant surfaces fol-
rials have gained increasing interest, first of all zirconia. Due to lowed by a loss of osseointegration due to an immunologic
their white colored surfaces, zirconia implants and abutments host reaction, called “bone loss”. Finally, extensive bone loss
are regarded esthetically superior compared to the gray col- leds to implant loss (see Fig YY).
ored titanium and have received broad scientific and clinical Therefore, trans- as well as supragingivally, implant/saliva
interest [8–13]. Nevertheless, titanium implant screws are still interfaces should have antiadhesive or antibacterial func-
the gold standard for oral implant applications, first of all due tionalities to impede biofilm formation. It has to be noted
to their surpassing biocompatibility and their ability to gain that a three-dimensional interphase is the primary biolog-
osseointegration, i.e., an intimate and direct contact with bone ical response to an initially only existing two-dimensional
by a cement-free connection at the light-microscopic level.The implant/biosystem interface. This dynamic formation of a
envisioned idea is still to achieve a direct contact between liv- transition zone between two phases with distinct width is
ing bone and the avital implant, aiming in this way to ensure associated for instance with hydration and macromolecular
the long-term function of the anchored prosthetic device [14]. adsorption [17,18].
Considering the transgingival nature of dental implants The challenge for advanced surface modifications in the
forming simultaneously several interfaces to the host biolog- trans-and supragingivally implant region is what has been
ical system, we termed this implant type “hybrid implant” termed “race for the surface”, the contest between bacte-
[15] consisting of: (a) the subgingival hard tissue interface of rial colonization and tissue integration of the same surface
the endosseous implant body, (b) the soft tissue transgingi- after implantation [19]. However, most studies until today
val interface at the implant neck and platform, and (c) the have been directed toward the improvement of the biomate-
interface to the oral cavity with its salivary environment at rial/bone interface and therefore, our knowledge in the field
the transgingival and the supragingival region, the latter that of the trans- and supragingival regions of implant screws and
region visible by eye containing the abutment or suprastruc- abutments is at best rudimentary.
42 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57

tology such interrelations were widely unknown or neglected.

2. From microroughness to nanoroughness Likewise, the available knowledge from basic surface sci-
and wettability – changes of paradigm at the ence about different biological responses to hydrophilic vs.
biomaterial/bone interface hydrophobic surfaces, e.g., in protein adsorption processes,
was obviously not considered for marketed surface modifica-
From today’s view it is astonishing that surfaces of implants tions of implants.
were not regarded important for osseintegration within the More than ten years ago, an inherent, highly hydrophobic
first decade of dental implantology. surface characteristic could be ascribed to typical combined
The role of surface characteristics gained importance since, grit-blasted and acid etched dental titanium implants [30].
in the early 80 s of the last century, Albrektsson et al. further Obviously unnoticed over decades, the continuous optimiza-
pioneered the concept of osseointegration by ascribing to sur- tion of the topography of titanium implants had generated
face properties a possible role for the biological response to microrough surfaces which induced very poor wetting; par-
an implant [14]. Requirements for ensuring a long-lasting and tially more hydrophobic than fluoropolymeric Teflon surfaces
direct bone-to-implant anchorage of dental implants in man [30,31]. Due to the observed high, beyond 120◦ water con-
were listed, encompassing implant material, implant design, tact angles, it became clear that the topography of implants
status of the bone, surgical technique, implant loading condi- was involved somehow in generating that poor wetting. Basic
tions, and the implant finish. The latter was further specified models of wetting science [32] suggested entrapped air below
by proposing rougher surfaces being beneficial compared to the wetting liquid contributing to an inhomogeneous and
smoother ones. However, the authors stated with caution that hydrophobic material/air–liquid interface.
cellular contacts, theoretically, could be dependent on the Meanwhile, several approaches are available to turn
implant surface. Furthermore, at that time, the importance hydrophobic implant surfaces into hydrophilic ones, usually
of this parameter was regarded difficult to evaluate. allowing the preparation of high energetic, superhydrophilic
The topography and roughness of implant regions adja- titanium surfaces with very low water contact angles (Fig. 1).
cent to bone has been optimized during the last four decades Our ongoing research, together with findings of other
to continuously improve the long-term success. A series of groups, recently evoked a change of paradigm: During the
surface modifications has been developed and applied on mar- last decades, research on implant surfaces focused on topo-
keted implants by different subtracting and additive methods, graphical features and tried to optimize first of all surface
including grit-blasting, acid etching by mineral acids, elec- microroughness. Research in this field is still of outmost
trochemical anodic oxidation, calcium-phosphate coatings importance, because many questions concerning the opti-
or several combinations of these techniques, e.g., combined mal topography for the bone and soft tissue contact remain
grit-blasted/acid etched surfaces. One important outcome of currently unanswered. In addition to surface topography, the
ongoing in vitro and in vivo studies focusing on the bone new paradigm includes now the role of wetting properties for
response was that moderately rough titanium surfaces being the interfacial biological responses and considers interrelating
modified to an arithmetic mean roughness Sa between 1 and effects of topography and wetting: phenomena such as rough-
2 ␮m surpassed smoother or even rougher surfaces in osseoin- ness induced wetting [33] but also very recent findings on the
tegration [20]. A recent study comparing surfaces with defined role of nanostructured surfaces and of synergistic effects of
microroughness confirmed beneficial effects of moderately nanostructuring and hydrophilicity [34–37].
rough surfaces on osteoblast differentiation and migration
[21].
Based on earlier surface science studies focusing on bio- 3. Measurement of surface roughness
materials, since the 90 s of the last century [22–24], apart from
surface topography and roughness, surface properties such as Whereas flat surfaces are easily accessible for topographical
chemical composition or surface energy have been reported analysis, dental implants have complex shapes, i.e., curva-
to influence interfacial reactions of a biomaterial [25] or more ture, threads, steps, making measurements difficult due to
specifically, the bone formation in vivo [26]. Schwartz and uneven, too small, or inaccessible areas. Stylus profilome-
Boyan outlined a change of paradigm from a restricted think- try [30,38], interferometry [39–42], stereo-scanning electron
ing to biocompatibility and mechanisms of bone formation to microscopy [38,40], or confocal laser scanning microscopy
rather studying the process in terms of wound healing [26]. [38,43] have been applied to quantitatively assess micro-
In short, this wound healing paradigm encompasses serum topography of implant surfaces. However, dependent on the
protein conditioning, the acute inflammatory response with chosen method, on the applied filters used for discriminat-
clot formation and release of wound healing factors, recruit- ing surface roughness from waviness, on the evaluation areas,
ment of undifferentiated mesenchymal cells to the surface, and the algorithms for the calculation of specific parameter
their attachment, proliferation, osteoblastic differentiation, values, the reported data are hardly comparable and their
followed by matrix vesicle production and maturation, and validity is unsure [40,44]. Guidelines for the evaluation of den-
calcification. tal implant surfaces [45] have boosted studies in this field,
Literature lacked systematic studies of surface energy or however, there is still little knowledge about the link of differ-
wetting properties of dental implant surfaces until the begin- ent height, spatial, hybrid or functional roughness parameters
ning of the 21st century. Whereas roughness-induced wetting to a relevant biological response at a specific implant site.
or non-wetting has been intensively studied in the fields of After decades of implant research, Sa values are proposed to
physics and physical chemistry for decades [27–29], in implan- be the only valid topographical data that allow a certain pre-
 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57 43

Fig. 1 – Different approaches enabling hydrophilization of dental implant and biomaterial surfaces to increase wettability
with aqueous host bioliquids.

diction of succesful osseointegration [20]. However, different strengthens the assumption that the hydrophobic nature is
topographies can have the same Sa-value [46] and therefore Sa caused by entrapped air inside the micropores underneath the
is a highly unspecific parameter, not very helpful in design- deposited water droplet. The surface area of such entrapped
ing advanced implant surfaces with an improved interfacial air can account for roughly three quarter of the entire sur-
behavior. Contrary, studies suggest that cell adhesion corre- face in contact with wetting water [50]. Consequently, only
lated better with frequency (spatial) roughness compared with a small portion of the hydrophobic microstructured implant
amplitude (height descriptive) parameters [47]. In addition to surface can be wetted during the initial contact with blood
limitations and vagueness of micro-roughness analysis and when inserting an implant clinically.
data interpretation, there are no guidelines concerning proper Questions arise about scale-dependent differences in con-
analysis in atomic force microscopical nano-roughness mea- tact angles [51], addressing a fascinating new field of research,
surements [36,48]. Furthermore, possible biologically relevant e.g., on micro- and nanowetting of microrough surfaces
topographical features, such as overhangs in the submicron- equipped with superimposed nanoscaled surface features.
range, cannot be detected by roughness analysis [49]. At Progress in this field of nanowetting can be expected by
present, the assessment of micron- as well as of submicron- recently available droplet generation systems that allow drop
and nano-roughness of dental implant surfaces is far from volumes in the lower picoliter range with corresponding small
being standardized and the prediction of biological perfor- evaluation areas of wettability.
mance is limited. An alternative and quite different approach is to analyze
wetting behavior by tensiometry [33]. Using this technique,
contact angles at geometrically defined sample surfaces can
4. Measurement of wettability be easily calculated based on force measurements during
immersion in a wetting liquid with known surface ten-
Similar to topographical analysis, wettability measurements sion. Furthermore, tensiometry enables the direct access
of implant screws is a challenge. Common approaches such to dynamic advancing and receding contact angles during
as the sessile drop method can easily be applied on flat sur- immersion/emersion loops. Wetting of dental implant screws
faces, however, the minimal possible drop size of conventional was succesfully tensiometrically analyzed by means of the
drop shape analytical systems precludes measurements on Wilhelmy balance method [52]. Even though the technique
very small areas of dental implants as between or on top is straightforward, the wetted length (perimeter) of a sample
of threads. In an alternative approach, small sessile drops has to be known. The exact perimeter at every position of an
were condensed on microrough titanium surfaces in an implant, however, is difficult to estimate due to system specific
environmental scanning electron microscope showing pro- thread geometries or cone-shaped designs of dental implants.
nounced hydrophilicity of blasted/acid etched surfaces [34]. Biomaterials in contact with bioliquids often are dynam-
It could be shown in this study that titanium, even if in ically wetted, i.e., there is a relative movement between the
a hydrophilic state below 90◦ water contact angle, as mea- solid and the liquid phase. For instance, this is clinically
sured by this technique on a microscopic level, can have a the case, when a dental implant is inserted into the wound
strong hydrophobic response if measured at ambient atmo- filled with blood and shear forces are generated between the
sphere by common macroscopic microdrop techniques. This implant and the body fluid. Therefore, dynamic wetting analy-
44 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57

Fig. 2 – Clinical example of extensive loss of osseointegration in dental implants due to inflammation.
Clinical findings of a peri-implantitis come along with swelling, suppuration and bleeding from the soft tissues, mostly. In
this case a fissula was detected with a periodontal probe, allowing a pain-free penetration up to 6 mm at both sides of the
implant. The radiograph of this implant, replacing an upper central incisor, clarifies a tulip shaped loss of bone around the
implant. In 2D projection only about one third of the implant bodys length is still osseointegrated. Today, such situations do
not allow a sufficient clinical/surgical treatment (effective decontamination of the exposed implant surface). Thus, implant
removal is the only appropriate measure to eradicate the inflammation. As indicated by the X at the right picture, the
implant surface was damaged by a surgical fraise during the implant removal. Such measures are necessary to leach the
implant from the remaining bone.

sis simulates wetting processes closer to the clinical situation bility, denoted “ageing” by some researchers [56]. Pioneering
compared to static measurements. Furthermore, besides wet- work in the field of surface cleanliness and surface depen-
ting, which is related to thermodynamic states, spreading is dent bioadhesion processes has been done by the research
an important parameter describing the kinetic changes of group of Robert E. Baier who has published an extensive series
surface and interface areas [53]. Therefore, one can assume of research publications during the last four decades. Early
that multivariant modelling of wetting and spreading would studies already reported about the importance of chemically
improve our understanding of initial phenomena at the bio- clean implant surfaces and the technique of radio frequency
material/bioliquid interface. glow-discharge (RFGD) treatments to achieve decontaminated
Of outmost importance in contact angle analysis is to know surfaces with high surface energy [57]. Baier et al. observed a
about which type of contact angle is actually measured [28]. strong influence of the initial surface state of cleanliness and
A simple measurement in a given system, e.g., by a static surface free energy of an implant on the healing process and
drop set carefully on a microrough surface, might yield contact generation of host tissue cells adjacent to the implant surface
angle values differing from that in equilibrated systems after [22,58]. RFGD has been used to both clean and sterilize implant
applying vibrations. The concept of equilibrated, most stable surfaces. Hydrocarbon layers, the most common residual con-
contact angles [28] is especially important if contact angles tamination on solid surfaces, can be efficiently stripped by this
should allow expedient surface energetic calculations. For this cleaning process [59].
purpose, most stable contact angles have to be transferred to Baier & Meyer reported that simple immersion of a freshly
actual contact angles by considering surface roughness and glow-discharge-treated sample in boiled, outgassed, sterile
inhomogeneity. The actual contact angle is nearest to the triply distilled water had been sufficient to retain the major
thermodynamic stable Young angle that is strictly related to share of the required surface properties for indefinitely long
ideal surfaces being smooth and chemically homogeneous. periods with different materials [60].
The actual contact angle can be inserted in the Young equation These early studies have been cutting-edge for following
[54] and used in different approaches enabling the estimation approaches to retain hydrophilicity of implant surfaces dur-
of total surface free energy or polar/apolar or acid/base parts ing longer storage times or to improve wetting by a direct
thereof [33]. treatment for immediate use.
On the one hand, as reviewed below, there are sev-
eral potential chair-side methods available that allow strong
5. Role of cleanliness for implant surfaces
hydrophilization of titanium implants by means of plasma
treatments or photofunctionalisation immediately before use.
Generally, titanium surfaces underly a reduction of bioac- ®
On the other hand, the SLActive -surface was developed
tivity in ambient atmosphere due to carbon contamination and launched in 2005 into the market from Institut Strau-
[55] accompanied by changes in surface energy and wetta-
 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57 45

mann (Basel, Switzerland). The SLActive-process prevents 6.2. Photofunctionalisation

contamination from the ambient atmosphere and conserves
an activated surface state by processing the implant screws The term photofunctionalisation encompasses in this review
after acid-etching under protective gas and storing them in both ultraviolet C (UV-C) and ultraviolet A (UV-A) triggered
saline [31,61,62]. After acid etching of titanium implants, an changes of surface states.
unsaturated surface state is expected. This high energetic In contrast to photocatalytically induced decontamination
surface state was characterized after storage in saline by a and hydrophilization upon UV-A irradiation, direct photolysis
very low carbon amount of 15 at.% compared to 35 at.% on upon UV-C works without use of a photocatalyst [56,71–73].
the unmodified blasted/acid etched surface and by superhy- UV-C irradiation shows the potential to improve the bone-
drophilicity with water contact angles of 0◦ [31]. In general, to-implant contact and the amount of bone growth during
perfectly clean surfaces are characterized by unsaturated the early healing period [74]. A retrospective clinical study
chemical bonds causing a high energetic surface state and, in has shown a two-fold shorter healing time for UV-C treated,
case of contact to the ambient atmosphere, strong bonding of hydrophilic implants compared to untreated hydrophobic
contaminants that lower the surface energy [63]. In contrast, ones without a significant change of the success rates [75].
activated titanium stored in aqueous liquid becomes hydrox- UV treatment also created superhydrophilic surfaces and
ylated and hydrated and resembles water, thus enhancing enhanced their initial attachment of osteoblast-like cells on
its wettability and improving interaction with the water shell zirconia [76].
around biomolecules [64]. Based on the photocatalytic effects of crystalline tita-
Lack of attention to surface energy and cleanliness may nium dioxide, particularly anatase, it becomes possible to
compromise the initial stages of tissue-healing after implan- gain superhydrophilicity upon irradiation of implants with an
tation [58]. Strictly speaking, any impurity, even caused anatase-enriched surface by UV-A light. Anatase has semicon-
by the manufacturing process, may be a possible trigger ductor properties with a band gap of 3.2 eV. Therefore, UV light
for unfavorable cellular or molecular responses resulting in with wavelengths below 400 nm enables the excitation of elec-
early marginal bone loss [65,66]. Such impurities were found trons and the creation of holes leading to various radicalic
throughout many implant systems on the market [67]. Based and anionic oxygen species. These reactive species induce
on this state of knowledge, an initiative of manufacturers and the photocatalytic decomposition of organic molecules. Pho-
researchers was launched recently [68]. tocatalysis is based on electrochemical studies in the early
70 s of the last century [77] and has been applied, e.g., in the
environmental field of water and air purification [78,79]. By
photocatalytic removal of hydrocarbon layers or other car-
6. Concepts for decontamination and
bonaceous species upon photoxidation and by an increase of
enhanced hydrophilicity
surface hydroxyl groups, there is an increase in hydrophilic-
ity leading in many cases to superhydrophilic surfaces. This
As described above, functional drawbacks of microrough den- hydrophilic conversion was published not before 1997 [80],
tal implant surfaces are on the one hand caused by roughness many years after the discovery of photocatalysis itself.
induced hydrophobicity [30,31], and on the other hand by Nanocrystalline antase thin films, prepared as implant
contaminations that further reduce the biologically available coating by reactive pulse magnetron sputtering, as implant
clean implant surface area. coating [81], were highly effective inducing superhydrophilic-
As reviewed below and illustrated in Fig. 1, several ity with water contact angles below 5◦ within 75 s of UV-A
approaches allow a decontamination and hydrophilization of irradiation at 25 mW cm−2 [82]. Based on this very fast kinet-
biomaterial and implant surfaces. Some of them are provided ics of reaching superhydrophilicity and on the observed
as chair-side pretreatment. slow kinetics of re-hydrophobization, such functional coatings
have a high potential for clinical applications [82].
Besides its hydrophilization effect, photocatalysis offers
6.1. Prevention of contamination a smart approach for the attack of attached biofilms caus-
ing peri-implant inflammations (peri-implantitis). The basic
A prominent example is the SLActive approach (see Chapter 5). idea is to photocatalytically decompose the proteinaceous
In contrast to cleaning-strategies, implants manufactured this conditioning films at the interphase formed between the bio-
way avoid contaminations ab initio after the manufacturing material surface and the bacterial layer. Studies have proven
process and retain a hydroxylated state and superhydrophilic- the successful photocatalytic decomposition of human serum
ity during storage. Being permanently hydrophilic, such albumin [82] and of salivary protein-rich pellicle films [83].
implants can be directly inserted into the bone after unwrap- Interfacial breaking points for biofilms induced by the pho-
ping from their original package. The basic idea of storage in tocatalytic attack possibly facilitate their removal by rinsing
liquid was also applied in a recent study which revealed that or soft mechanical treatments. This is of high clinical inter-
blasted and acid etched titanium keeps its superhydrophilicity est, because in course of current mechanical peri-implantitis
for 28 days after etching when stored in methanol [69]. treatments (Fig. 2), the implant surface structure can be
At present, SLActive is one of the best investigated superhy- strongly damaged and functionality be limited dependent
drophilic implant surfaces. Studies indicate that this surface on the cleaning procedures [84,85]. Loss of the original sur-
type improves the initial reactions of healing resulting in an face properties might increase the risk of re-colonization of
accelerated integration [62,70].
46 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57

in their hydrophilization kinetics, indicating that surface

microstructure and roughness are important factors that have
to be considered when chair-side methods are developed to
clean implant surfaces and make them likewise hydrophilic
[88]. In this study, the fastest hydrophilization kinetics was
observed with SLA which becomes superhydrophilic within
2 min exposure to plasma or 8 min UV-C treatment. In con-
trast, SL needs 10 min with plasma or 26 min with UV-C to
reach such low contact angles. On basis of the experimen-
tal settings applied in our study, plasma treatments allowed
faster and more extensive hydrophilization compared to UV-C,
confirming similar results of Henningsen et al. [89].
Whereas photocatalysis attacks biofilms at the mate-
rial/biofim interface, plasma methods attack from top. Here,
it could be shown that argon/oxygen plasma in combination
with mechanical brushing is capable to clean rough titanium
surfaces better than solely applied plasma or brushing, thus
Fig. 3 – Kinetics of hydrophilization of polished (P),
enabling an improved osteoblast response [90].
sandblasted (SL), acid etched (A) and combined
Upon argon/oxygen cold (non-thermal) plasma treatments
sandblasted/acid etched (SLA) titanium samples. The
at atmospheric pressure, osteoblastic cells showed signifi-
samples were treated by UV-C or oxygen plasma at 2 min
cantly increased spreading [91]. If argon plasma was used for
intervals, interrupted by contact angle measurements
cleaning of implant abutments before insertion, peri-implant
followed by nitrogen drying. Superhydrophilicity is defined
crestal bone and soft tissue maintenance were supported
for contact angles <10◦ . Experimental: 2 ␮l sessile drops
and bone resorption reduced as shown in a 5-year clini-
were set on the surfaces and the contact angles were
cal study [92]. Choi et al. have shown very recently that
analyzed at a DSA 10 MK 2 drop shape analyser (Krüss,
both atmospheric pressure air plasma and UV-C treatment of
Germany). UV-C of 15 mW/cm2 was applied in an
microrough titanium are able to reduce hydrocarbon contam-
irradiation cube (UV-C cube, Hoenle, Graefelfing, Germany).
inations, increase hydrophilicity, diminish negative surface
Oxygen plasma was generated in 0.3 mbar vacuum in a
charge, and improve albumin adsorption as well as osteoblast
plasma chamber (DentaPlasImp, Diener electronic,
attachment [93].
Ebhausen, Germany) at 40 W.
In addition to studied plasma effects on titanium,
plasma techniques have also been applied to modify sur-
faces of alternative implant or abutment materials, such as
bacteria and impede successful re-osseointegration. During polyetheretherketone [94] or zirconia [95].
peri-implantitis treatments, one additional advantage of pho-
tocatalytic surface modifications such as anatase coatings is 6.4. Further hydrophilization treatments
the opportunity of gaining a superhydrophilic surface upon
irradiation that should support re-osseointegration of exposed Alkaline treatments turned microrough titanium from strong
implant surfaces. hydrophobic to superhydrophilic [96–98] indicating similarly
To sum up, both effects, photocatalytic attack of biofilms to the chemical modification of SLActive [31] that roughness
and hydrophilization, are of great interest in the field induced hydrophobicity can be overcome by chemical modifi-
of implantology. Whereas in dentistry blue-light lamps cations. Relations of microstructure and wettability were also
in the range of 390 nm–500 nm at intensities of about shown by turning hydrophobic titanium substrates with dif-
600–2000 mW/cm−2 are in common use for the polymerization ferent microtopographies into hydrophilic by thin film coating
of light curing resin based composites, shorter wavelengths with polyelectrolytes [99].
have to be handled with care due to a high risk for tissue
cell damage. Therefore, red-shifted photocatalytic layers that
can be activated at longer wavelengths than UV-A are of great 7. Roughness and wettability of dental
interest to enhance the clinical acceptance of therapeutic light implants on the market
irradiation during clinical treatments [86,87].
Marketed dental implant surfaces show great variations in
6.3. Plasma treatments their surface modifications: besides blasted/etched surfaces,
there are only blasted, only etched, anodically oxidized sur-
Superhydrophilization and decontamination of titanium faces or implant surfaces with different other treatments, e.g.,
implant surfaces can also be achieved by plasma treatments. modification in fluoride solutions, available [100,101]. Besides
In a recent study, we compared the kinetics of hydrophiliza- variations in blasting media or etching conditions, some of
tion of titanium samples with different microstructured these surfaces are further modified by, e.g., calcium phosphate
surfaces upon oxygen plasma and UV-C treatments (Fig. 3). modifications, often applied as nano-coatings.
Combined blasted/acid-etched (SLA), only blasted (SL), only Typical blasted/etched titanium surfaces show a hierar-
acid-etched (A) and smooth titanium surfaces (P) differed chical surface structure, characterized by different levels of
 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57 47

roughness with small 0.5–3 ␮m pores and compartments tion through a temporary connective tissue scaffold, termed
resulting from the etching process superimposed to the osteoconduction, is the first phase of the osseointegration pro-
macrorough structure 20–40 ␮m in size achieved by the blast- cess [113]. He subdivided osseointegration into three distinct
ing process [30,31,40]. On hydrophilic blasted/etched SLActive phases [113]: after osteoconduction, de novo bone formation is
implant surfaces, the existence of nanostructures was proven initiated by differentiating osteoblasts which secrete a miner-
[36,37]. On anodically oxidized surfaces, volcano-shaped alized non-collagenous cement line onto the surface. Finally,
micropores in various sizes are scattered on a relatively flat de novo bone formation results in the assembly of a col-
surface. The pore size has been found to be 1–2 ␮m, however, lagenous matrix overlying the initially formed cement line,
even smaller, nanosized pores can be detected [40,102]. followed by mineralization of the collagenous matrix. A third
Compared to topographical studies, only a small num- phase, bone remodeling, similar to the process at bone inter-
ber of reports is available showing wetting or surface energy faces, leads to permanent de novo bone formation at discrete
data of dental implant surfaces. In a recent study, wetting sites at the implant interface.
properties of nine implant systems from eight different man- During early reactions of wound healing, two factors have
ufacturers were investigated by tensiometry [52]. Three out been identified to play a possible role for the histological and
of nine systems only were hydrophilic during the initial histometric differences between hydrophilic and hydrophobic
wetting phase with contact angles below 90◦ , one of them implant surfaces observed in vivo. The first relates to differ-
was superhydrophilic. The contact angles of the hydrophobic ent patterns of adsorbed plasma proteins that exert specific
implants ranged from 100◦ to 138◦ . The study has shown that up or down regulations of genes expressed by the adjacent
a hydrophobic characteristic is not limited to blasted/etched progenitor cells [117–119]. The second factor concerns a more
surfaces but seems to be a more general characteristic of stabilized blood clot on hydrophilic surfaces without disin-
microstructured titanium. An initial hydrophobicity, as shown tegration of the clot as observed on hydrophobic surfaces
in this study for most implants, is regarded unfavorable for the [120]. Furthermore, Schwarz et al. showed that angiogene-
initial biological response in blood contact [62]. sis was enhanced on hydrophilic surfaces during early stages
Thus, many current implants might benefit from concepts of osseointegration [121]. Actually, fast vascularization seems
allowing chair-side hydrophilization as outlined in Chapter beneficial for bone formation because osteogenic cells have
6. A recent study reported the effects of UV-A and UV-C been observed to arise from pericytes adjacent to small blood
irradiations on different marketed dental implants manufac- vessels [122,123].
tured from titanium, zirconia, or polyetheretherketone (PEEK) The altered protein conditioning of hydrophilized implant
[103]. PEEK is one of the available polymers exhibiting high surfaces can influence different proteinase cascades dur-
biocompatibility. It has been increasingly considered as a bio- ing inflammation and wound healing. Triggered processes
material for a variety of biomedical applications including include, besides coagulation, the complement system, fib-
dental, orthopaedic, and cardiovascular devices [104–107] as rinolysis, and the kallikrein-kinin system as well as the
well as for prosthetic suprastructures [108]. Due to its excellent adhesion and activation of blood cells ([124] and references
mechanical properties, PEEK is under discussion as a potential therein). Studies from our group have shown that thrombo-
dental implant material, too [109,110]. cyte activation, measured as release of beta-thromboglobulin,
as well as activation of the complement complex iC3b, were
significantly decreased on hydrophilic SLActive compared to
8. Implant surfaces modulate the hydrophobic SLA surfaces [125]. Moreover, the cell adhesion
bioresponse promoting effect by fibronectin bound to the surface was
more pronounced on the hydrophilic variant. SLActive sam-
Implant surfaces determine primary interfacial reactions with ples incubated with fibronectin in a concentration present
blood components, bone, epithelial and connective tissue cells in human blood exhibited a significantly enhanced amount
[20,111,112]. Different wound healing processes, macromolec- of cell binding RGD-sequences compared to the hydrophobic
ular adsorption, as well as cell adhesion, proliferation, and reference SLA [126].
differentiation are concerned. Such studies indicate that there is a distinct effect of
hydrophilicity on blood/implant and, consequently, on dif-
8.1. Initial implant/biosystem interactions – blood ferent cell/implant interactions. However, it is not clear now
contact which degree, e.g., of inflammation is ideal for an optimized
wound healing and subsequent improved osseointegration
The cylindrically or conically shaped holes for the insertion of of implants. Recent studies indicate that a combination of
dental implants are immediately filled with blood due to rup- nanostructures and hydrophilicity improved the condition-
tured blood vessels and vascular trauma of the bone. Wound ing of titanium surfaces by blood protein adsorption and also
healing, a prerequisite for successful osseointegration of an enhanced blood coagulation better than each single modifica-
implant in a bloody environment, comprises a series of molec- tion alone [127].
ular and cellular events [26,66,113–115]. Fibrin clot formation
is associated with most wound healing processes and seems 8.2. The cellular and tissue response
to be linked to initial osseointegration reactions. The blood
clot serves as a bridging scaffold for mesenchymal stem cells Surface properties such as micro-roughness [128], surface
migrating into the wounded tissue enabled by the secretion energetic and wetting characteristics [129] or combinations
of fibrinolytic enzymes [116]. According to Davies, this migra- of specific topographical and wetting properties [99,130]
48 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57

Fig. 4 – Field emission gun scanning electrone microscopic (FEG-SEM) graphs (magnification ×10,000 and ×100,000) of a
microstructured implant surface superimposed by a submicron, partly nano-scaled anatase film: (a) blasted/acid etched
® ®
original implant surface (Promote , Camlog Biotechnologies AG, Basel, Switzerland); (b) Promote surface modified with a
highly pure anatase layer. Polycrystalline 500 nm anatase thin films were prepared by reactive pulse magnetron sputtering
in bipolar pulse mode with a frequency of 20 kHz as previously described in detail [82].
All samples for FEG-SEM (Zeiss DSM 982 Gemini, Zeiss, Germany) were sputter-coated by a 0.3 nm thick layer of Pt/Pd
(80/20).The SEM images were recorded using an acceleration voltage of 3 kV [103].

influence cell spreading, differentiation and local factor pro- gested by introducing both micron- and submicron-scaled
duction. structural features [132]. Actually, hierarchically structured
A micron-scaled roughness contributes to cell attach- implant surfaces and the specific role of nanostructures on
ment, spreading and differentiation because osteoblasts and bone formation are under intense research [134–137].
mesenchymal stem cells can directly interact with the sur- Nanostructures on titanium have been created by different
face features [131]. Superposition of a near submicron-scaled approaches, such as oxidative nanopatterning by acid etching
roughness has been found to enhance local factor production in mixtures of sulfuric acid and hydrogen peroxide [138], by
[132]. At this scale, cell membrane receptors can recognize sur- exposing titanium samples to flowing synthetic air [34,139],
face adsorbed proteins, which in turn are modulated by the electrochemically by anodic oxidation [140], by processing
nanostructures on the surface [131]. Generally, cells come into samples after acid etching under protective gas and storing
contact with their environment via transmembrane recep- them in saline [37], by plasma etching [141], or by physical
tors, e.g., integrins, binding to natural extracellular matrix vapor deposition techniques [82].
constituents, or to an (already conditioned) implant surface However, for porous, tubular, or pit like shaped nanostruc-
[26,130,133]. tures, it is widely unknown which dimensions, aspect ratios
In addition, synergy towards an improved bone response or distribution on a biomaterial surface are favorable for an
between surface topography and surface energy has been sug- optimized functionality of an implant at its biological inter-
 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57 49

Fig. 5 – Influence of UV-activated anatase coating (see Fig. 4) on sample surface coverage by human osteoblasts. (a)
® ®
blasted/acid etched original surface (Promote , Camlog Biotechnologies AG); (b) Promote surface sputter-coated with
2 ®
polycrystalline anatase and activated by UV-A irradiation (382 nm, 25 mW/cm , 3 min); (c,d): Cell coverage of Promote
®
sample (left) and anatase-coated Promote surface (right) by human osteoblasts (SAOS-2) after 4 days in culture. Arrows
indicate the borderline of the anatase-coated area due to shadowing effects caused by the specimen mount during the
coating process. Crystal violet staining, ×10.
Photometric quantification of the eluted crystal violet stain revealed a 7fold increased cell coverage on the anatase-coated
®
samples (710 ± 130%), compared to 100 ± 18% on the original Promote surface. Bars represent means and SD’s from 3
independent experiments with 3 samples in each group, respectively.

face. Available studies indicate that proteins as well as cells after seven days of cell culture and elongated protein aggre-
react sensitive to nanoscaled surface features [142–144]. For gates were found mimicking the wormlike nanostructured
example, fibroblasts could discriminate dot like nanostruc- surface.
tures with an average height of 6 nm from wormlike structures On the protein level, Gonzales-Garcia et al. investigated
with an average height of 3.2 nm and preferred the latter, indi- fibronectin adsorption and distribution on nanoscaled poly-
cated by earlier adhesion and increased proliferation [144]. On meric topographies with 14, 29, and 45 nm deep pits [143].
both nanostructures, the extracellular matrix was different Fibronectin adsorption was about 50% higher on the surface
50 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57

according to increased implant pull-out forces after 4 and 8

weeks healing time, suggested synergistic effects of nanos-
tructures and hydrophilicity [36]. Recent findings also indicate
that nanostructures as present on the SLActive surface can
even delay differentiation processes if hydrophilicity is absent,
suggesting that beneficial effects of nanostructured titanium
surfaces will be dependent on hydrophilicity [130]. Looking
for a deeper understanding of the different bioresponses to
SLActive vs. SLA, a very recent study found thinner carbon
contamination films on SLActive (0.8 nm) compared to SLA
(1.6 nm) suggesting an impact of the different contamination
films on the blood response, leading to accelerated osseointe-
Fig. 6 – Influence of different microstructures, gration [147].
superimposed anatase coating and UV-activated anatase Gittens et al. reported about the role of nanotopographical
coating on proliferation of human osteoblasts. Titanium features and of surface wettability on the osteoblastic differ-
sample discs (cp Ti grade 4, 10 × 1 mm) with a sandblasted entiation of osteoblast-like MG 63 and of mesenchymal stem
(S) surface were either acid etched (S/A) or modified with an cells [34]. The authors have shown that the recognition of sur-
anatase coating by Physical Vapour Deposition (S/ANA). face nanostructures and subsequent cell responses depend
Half of the anatase-coated samples were photocatalytically on the differentiation state of the osteoblast cells. Further-
hydrophilized by UV-A irradiation (382 nm, 25 mW/cm2) for more, the observed responses seemed to be partly modulated
10 min (S/ANA-UV). Human osteoblasts (Saos-2) were by differences in the surface wettability of combined micro-
seeded onto the samples (n = 4/group). Cell proliferation /nanomodified surfaces compared to solely microstructured
was monitored via mitochondrial metabolic activity (XTT) surfaces. Thus, there are complex interfering effects between
24 h, 48 h, 72 h and 96 h after seeding. topography and wetting on the one hand, the latter deter-
Proliferation of osteoblasts was significantly enhanced on mined by surface chemistry including carbon contaminations,
S/ANA compared to (S) and (S/A) at all points of time tested. and on the other hand between the aforementioned param-
UV-A irradiation (S/ANA-UV) increased the proliferation eters and biological responses. Actually, in a recent animal
rate even further. study, microrough implants superimposed with a calcium-
phosphate nanotopography outperformed pure microrough
surfaces in their bone anchorage even in compromised bone as
found in hyperglycemia [148]. Nano-topographies also play an
important role for bacterial adhesion [149,150]. Keeping bacte-
ria associated inflammations in mind, a deeper understanding
with 14 nm pits compared to the deeper ones and on this of oral bacterial colonization onto trans- and supragingival
nanosurface the tops were preferentially conditioned at low implant zones is indispensable. A more effective biofilm con-
protein concentrations. In the same study, the distribution of trol by advanced surface designs of dental implants including
focal adhesions of osteoblasts was influenced by the pit size: novel nano-topographies should further improve their long-
the size of the adhesion plaques increased with increasing pit term performance and survival rates.
size.
Studies of our group have shown that nanocrys- 8.3. Biomimetic aspects in the fields of implantology
talline, hydrophilized thin films of anatase on typical
sandblasted/acid etched titanium significantly enhanced Current health-related research is following biomimetic
osteoblast cell coverage compared to the unmodified, original approaches in learning how to create new biocompatible
blasted/etched surface (Figs. 4 and 5). Similar effects were materials with nanostructured features [151]. New bone for-
demonstrated on titanium surfaces structured solely by mation is linked to bone resorption, e.g., by releasing factors
sandblasting: Compared to the original blasted surface, cell like transforming growth factor beta (TGF-ß) from the bone
proliferation over 4 days culturing time was significantly matrix during resorption inducing the migration of osteoblast
enhanced by an additional, superimposed nanostructured precursors, bone mesenchymal stem cells, to bone resorptive
anatase layer. The proliferation rate was further increased by sites [152]. Osteogenic responses as observed on microrough-
UV-induced photohydrophilization [145] (Fig. 6). ened titanium surfaces, i.e., decreased cell numbers and
Other studies indicated that the occurrence of nanos- enhanced differentiation, is basically driven by mimicking
tructures seems to influence osteoblast lineage cells and in pit structures at natural bone surfaces that are created in
many cases be advantageous for promotion of regeneration course of osteoclast activity [153]. The natural submicron
[36,139,146]. scaled three-dimensional complex surface of the deminer-
Nanostructures were identified on the marketed super- alized bone matrix that resulted from osteoclast resorption
hydrophilic SLActive surface [37]. The question arose if not becomes the recipient surface for new bone formation [154].
the superhydrophilicity itself but these nanostructures might Nano (submicron), micron, and macro (coarse-micron) scale
have caused the observed beneficial reactions towards an ranges of implant topographies were recently related to scale
accelerated osseointegration compared to the hydrophobic ranges found at natural remodeling sites at bone: Submicron
SLA surface. Recent results of an animal study, however, scale features <1 ␮m with undercuts that allow deposition of
 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57 51

Fig. 7 – Scheme showing the relevance of characterization of surface properties at the very point of time of surgical
insertion. During storage time, surface properties might be modulated compared to their state directly after industrial
manufacturing. They can be altered again by chair-side treatments immediately before implantation.This clinically relevant
surface state is directly related to initial reactions at the biomaterial/host interface, such as protein conditioning,
complement activation, blood cell interactions, clot formation, and inflammatory response.

bone matrix, micron scale surface features <10 ␮m mimick-

ing a single osteoclast resorption pit, and macro scale cavities
9. How to optimize the dental hybrid
>10 ␮m, naturally formed by resorption activity of one or more
implant – what have we learnt?
osteoclasts [49]. These hierarchical scales as observed on nat-
ural bone remodeling sites can be mimicked by blasting, acid As reviewed by Bruinink et al. [142], wettability and nanos-
etching, and different nanotechnological processes, respec- tructuring both affect protein conditioning of biomaterials,
tively. However, to mimic nanosized features with undercuts cell/surface interactions and osseointegration. Nanomedicine,
as observed at remodeling sites is challenging, especially if even though still in its infancy, is going to revolutionize
surface chemistry should be considered besides topographical medicine. A dramatic growth in nanomedicine research is
aspects. Hierarchical surface structures with some undercuts expected in the next decades on medical sectors such as
at least at the smallest submicron features might exist in diagnostics, drug discovery and delivery, tissue engineering,
two possible wetting states, i.e., complete wetting or unwet- imaging agents, and implantable devices. As shown above,
ting [27]. Both states, intial hydrophobicity and subsequent recent insights in the impact of nanostructured surfaces and
complete wetting were observed on hierarchically structured, their wetting behavior give rise to advanced surface designs
blasted/acid etched titanium implant surfaces in course of for improved tissue regeneration. Furthermore, biomimetic
dynamic contact angle analysis [30]. Anyway, it should be con- approaches will push forward the development of surfaces
sidered in future studies on advanced biomaterial surfaces designed to imitate successfully natural surfaces and to stim-
that both topography and surface chemistry influence the wet- ulate balanced interfacial reactions. Nevertheless, one should
ting outcome and hereby the bioresponse. be aware that despite growing knowledge in macromolecular
Following biomimetic approaches, it becomes more clear and cellular interactions with biomaterial surfaces, clear links
that even though cells have dimensions in a micrometer scale, between surface properties of materials used in biomedicine
they evolve in vivo in close contact with the extracellular and implantology, their impact on the adsorbed protein layers,
matrix, a substratum with topographical and structural fea- and their influence on cells remain far from being understood
tures in nanometer size. Therefore, nanostructures that mimic [143]. Furthermore, there is a pronounced gap between in vitro
on biomaterials the natural environment of cells might be able results and the performance of implants in the individual
to interact with cells at a molecular level to control effectively patient. This gap has to be overcome by more sophisticated
processes of tissue regeneration, such as cell adhesion, prolif- laboratory study designs in order to improve the still lacking
eration or differentiation [155]. prediction of the in vivo situation [142].
52 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57

As highlighted in Fig. 7, an important issue for further possibly be at disadvantage concerning blood protein adsorp-
developments is to consider and likewise ensure that desired tion that should be favored near 65◦ water contact angle.
surface states are stable and available at the point in time Indeed, it was shown that material surfaces with moderate
of surgical insertion. Storage of implants might on the one water contact angles in the range between 30◦ –60◦ favour
hand be responsible for re-contamination after industrial pro- serum protein adsorption, protein exchange of preferentially
cessing and changes in the clinical performance. On the other adsorbed albumin by cell adhesive serum proteins such as
hand, storage can even prevent such contamination and pre- fibronectin or vitronectin and eventually the adhesion of cells
serve activated, higher energetic states. Eventually, chair-side [166].
treatments can be applied to assure a desired degree of clean- Therefore, it is a future challenge to give different implant
ing or hydrophilicity. surface areas different hierarchical designs including nanoto-
Nevertheless, the surface itself is only one major factor of pographical features. Together with specific surface energetic
implant success among others. Early and late implant failure and wetting characteristics including a defined carbon con-
– in terms of bone loss – can also be attributed to the sur- tamination state, hard and soft tissue integration should be
gical approach (surgical skills/placement, instruments, bone optimized further.
substitutes), patient factors (bone quality, systemic health, Likewise, a topic of outmost relevance in biomedicine is
bruxism, oral hygiene and health maintenance), and physi- bacterial caused infection in course of biofilm formation at
cal impact (loading, tension, type of restoration, region of jaw) implant sites. Here, recent studies also suggest an influ-
[156–160]. However, improved surface characteristics might ence of nanotopography and wettability on bacterial retention
compensate the impact of the aforementioned factors when [167–169]. Current own studies focus on biomaterial/bacterial
the interface reactions facilitate a stable foreign body equi- interactions [170] and, besides the presented photocatalytic
librium and a robust osseointegration [65]. This implies that approach, on antibacterial surface modifications for the trans-
clinical long-term observations are necessary to finally judge and supragingival part of dental hybrid implants [171,172].
the performance of novel surfaces. Due to the generally low To meet this challenge, interdisciplinary collaborations
number of failures over time in marketed implants, it could should be intensified in the fields associated with biomate-
be worthwhile to set up randomized controlled clinical trials rials research such as medicine, nanomedicine, biomedical
covering the rather unfavorable clinical situations [161,162]. engineering, physical chemistry, and clinical testing.
Furthermore, animal studies might also reveal differences in
short-term bone loss when inducing an inflammation of the
transmucosal area [16]. 10. Conclusions and future perspectives
Regarding the concept of the transmucosal dental hybrid
implant [15] that faces hard and soft tissue and in the trans- Ongoing research and findings evoked a change of paradigm
and supragingival implant or abutment regions also saliva and during the past decade: Instead of focusing mainly on topo-
bacteria, it becomes obvious by our current state of knowledge, graphical features, in the first place surface roughness, the
that these specific interfaces require specific surface modifi- new paradigm includes now the role of wetting properties for
cations. This is strengthened by studies that show, e.g., at the the interfacial biological responses and considers interrelating
nanometer scale, different adhesion responses of fibroblasts effects of topography and wetting, i.e., micro- and nanorough-
and osteoblasts [163]. Thus, different cells seem to give differ- ness induced wetting phenomena. Very recent findings also
ent responses on nanotopographical features. Furthermore, identified synergistic effects of nanostructured surfaces and
surface energy and wettability of an implanted material rep- hydrophilicity on the biological response, pushing forward
resent key parameters with which cell behavior at the material once more international research in this exciting field. Within
interface can be altered [142]. This is intriguing because at the next decade one can expect the availability of smart, tai-
present many processes aiming to improve the wetting behav- lored surfaces that will optimize the respective interfaces of
ior do not allow a tailored wetting characteristic but result hybrid implants according to their functional requirements in
in a high energetic state that leads to superhydrophilicity. a highly specific way.
However, it is not for sure that such high energetic states Novel findings on wetting and nanoroughness are not
are an optimum for biological interactions. Vogler pointed only relevant in the field of dental implantology. The current
out that water at solid surfaces shows a less-dense struc- and upcoming results have an impact on all maxillofacial or
ture at hydrophobic compared to a more dense structure at orthopedic implant surfaces that require specific osteogenic
hydrophilic surfaces with a limit near a wetting tension of 30 functionality for short or long-term endosseous integration
mN/m, corresponding to a water contact angle of 65◦ and 72.8 just as on cardiovascular implants in constant contact with
mN/m water surface tension [18,164,165]. Surfaces with a wet- blood.
ting tension >30 mN/m are denoted hydrophobic, <30 mN/m
hydrophilic, with consequences for the bioresponse because
water bound to surfaces must be replaced by adsorbing pro- Acknowledgments
teins. Usually, hydrophilicity is separated from hydrophobicity
by the change of sign of the wetting tension at water contact Funding of our research projects in this field over years
angles of 90◦ . Following Vogler, the border is shifted here to is gratefully acknowledged: Funding by the International
a moderate hydrophilicity at around 65◦ contact angle and Team of Implantology (ITI, Basel, Switzerland), by the
explains protein repellent behavior of surfaces with contact German Research Foundation (Deutsche Forschungsgemein-
angles <65◦ . In this regard, superhydrophilic surfaces might schaft, Bonn, Germany), by the Baden-Württemberg Stiftung
 d e n t a l m a t e r i a l s 3 4 ( 2 0 1 8 ) 40–57 53

(Stuttgart, Germany), by the Camlog Foundation (Basel, [18] Vogler EA. Structure and reactivity of water at biomaterial
Switzerland), and by intramural fundings of the University surfaces. Adv Colloid Interface Sci 1998;74:69–117.
Hospital Tuebingen. LL is supported by the China Scholarship [19] Gristina AG. Biomaterial-centered infection: microbial
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