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Sandra Sánchez-Salcedo, Montserrat Colilla, Isabel Izquierdo-Barba, et al.

control and prevent bacterial contamination of im- the use of nanostructured surfaces with inhibited bac-
plants. One strategy consisted of tailoring the antibac- terial adhesion could represent a challenging alterna-
terial properties of the implant surface. Thus, different tive to antibiotics [17–19] . Varied surface modification
surface modifications and coating techniques have techniques have been widely used in the fabrication of
been proposed, such as direct impregnation with anti- artificial antibacterial surfaces [20–22] . These surfaces
biotics, immobilization of bactericidal agents or coat- comprised a range of nanotubes and nanoparticle-
ing with antimicrobial active metals such as copper based surfaces, and nanostructured coatings produced
and silver, nitric oxide-releasing materials, and TiO 2 by glancing angle deposition technique by magnetron
[6]
films . Nonetheless, whatever antimicrobial strate- sputtering (MS-GLAD) [23,24] .
gies used, implants must fulfill the non-fouling re- The potential of these antibacterial strategies into
quirements or biomacromolecules and dead microor- the bone tissue engineering (BTE) landscape would be
ganisms would easily accumulate on the implant sur- essential in manufacturing advanced three-dimensional
face and hinder the antimicrobial activity of its func- (3D) scaffolds. The different techniques used in the
[7]
tional groups . For this reason, great research efforts manufacturing of scaffolds must permit an accurate
have been devoted to develop new strategies to modi- control of different length scales from nano, micro to
fy the surface of biomaterials to provide antibacterial macro [25] , attending to clinical needs. 3D scaffolds for
: (i) hi-
adhesion capability. With the aim of hampering the BTE must fulfill the following requirements [26]
attachment of microorganism onto surfaces, a widely ghly interconnected pore networks to allow cell growth,
investigated method consisted of grafting surfaces nutrients supply and metabolic waste; (ii) both bio-
with hydrophilic polymers, and highlighting polye- compatible and bioresorbable behavior with tunable
thylene glycol (PEG) derivatives. Steric repulsion degradation and resorption rates to ensure tissue re-
caused by a water hydration layer formed via hydro- placement; (iii) appropriate surface chemistry for sele-
gen bonding has often been proposed to explain the ctive cell attachment, proliferation, and differentiation;
resistance of hydrophilic surfaces to protein and bac- and (iv) mechanical properties similar to those of the
terial adhesion [8,9] . A major concern that limits biolog- tissues at the implantation site [26,27] .
ical applications of PEG is that this polyether autox- This review begins with a description of the differ-
idizes relatively quickly [10] , which made PEG coatings ent recent surface modification strategies aimed at
having restricted attainment in preventing long-term inhibiting bacterial adhesion. Among the diverse ap-
biofilm formation. proaches, we centered on the chemical modification of
Recently, zwitterionization of biomaterials has em- biomaterials via zwitterionization, and the modifica-
erged as a groundbreaking strategy to confer surfaces tion of metal implants by tailoring its surface nanoto-
of high resistance to nonspecific protein adsorption, pography. In addition, this review focused on the po-
[9]
bacterial adhesion and/or biofilm formation . Zwitte- tential application of these antibacterial strategies in
rions are characterized by owning an equal number of BTE. To this aim, the more sophisticated techniques
both positively and negatively charged groups within for the fabrication of 3D scaffolds are overviewed.
a molecule hence maintaining overall electrical neu- 2. Bone Implant Infections
trality. The non-fouling ability of zwitterionic mate-
rials, as in the case of hydrophilic materials, is corre- In this section we overviewed the recent advances
lated with a hydration layer on the surface, since a developed to date concerning the design and devel-
closely bound water layer forms a physical and ener- opment of zwitterionic surfaces and nanostructured
getic barrier to avoid bacterial adhesion. Since zwitte- coatings to inhibit bacterial adhesion and biofilm for-
rionic materials contain both positive and negative mation onto implantable biomaterials.
charged units, it can bind water molecules even more
strongly than hydrophilic materials via electrostatical- 2.1 Zwitterionization of Biomaterials
ly induced hydration, becoming an important part in Zwitterionic materials are very promising next-gen-
affording interfacial bioadhesion resistance [9,11] . eration biomaterials with a wide variety of potential
On the other hand, it has been demonstrated that biomedical applications. Herein, we summarized the
surface nanotopography and architecture plays an es- methods reported to date to provide metal substrates
sential role in bacterial attachment and biofilm forma- and bioceramics of zwitterionic nature aimed at de-
tion [12–15] . In fact, Campoccia et al. [16] indicated that signing bacterial anti-adhesive biomaterials.

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