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

[8,9]
be divided into four stages : (i) treating of the bare potential measurements. The capability of these mate-
metal with ultraviolet (UV) light; (ii) immobilization rials to inhibit bacterial adhesion was in vitro eva-
of either dopamine (D) or an organosilane (Si); (iii) gra- luated by simulating severe inflammation/infection
fting of the initiator, 2-bromoisobutyl bromide (BiBB); conditions, which are usually associated to a decrease
and (iv) polymerization of SBMA monomers from the in normal pH values [45] . In vitro bacterial adhesion
BiBB-tethered surface via ATRP. In vitro bacterial assays using E. coli indicated that bacterial adhesion
adhesion assays were tested using two of the most in zwitterionic SBA-15 was reduced to ca. 93% rela-
commonly seen clinical bacteria, E. coli and S. epi- tive to that for pure silica SBA-15. Moreover, in vitro
dermidis. Bacterial adhesion tests on pTi surfaces in- tests with cultured human Saos-2 osteoblasts were
dicated that bare metal surface was fully covered by E. performed to investigate the biocompatibility of zwit-
coli and S. epidermidis after 24 hours of assay [36] . terionic materials at 7.4, i.e., once normal physiologi-
However, very few bacteria were attached to SI- cal pH conditions have recovered. The results demon-
ATRP-treated surfaces, reduced to ca. 95% relative to strated that zwitterionic SBA-15 exhibited good bio-
uncoated pTi surfaces. This opened up promising ex- compatibility with Saos-2 osteoblasts adhering, proli-
pectations in the field of metallic implants. ferating and maintaining its morphological and func-
.
(2) Zwitterionization of bioceramics tional characteristics [45]
Bioceramics are excellent candidates to manufacture Recently, the design and synthesis of a new zwitte-
bone-like scaffolds [38,39] . It can be designed to release rionic SBA-15 type bioceramic with dual antibacterial
biologically active molecules to repair, maintain, re- ability has been reported [46] . Its non-fouling capability
store or improve bone functions. Different strategies was derived from the inherent zwitterionic nature of
have been developed to provide bioceramics of zwit- the surface, while the bactericidal capability resulted
terionic nature aimed at inhibiting bacterial adhesion from its capability to host antibiotics into the meso-
and preventing bone implant infections. In this case, pores. In this case, zwitterionic SBA-15 mesoporous
inhibition of bacterial colonization must be compati- material was synthetized by using an alkoxysilane be-
ble with adhesion of bone-forming cells to allow os- aring primary and secondary amine groups (N-(2-am-
seointegration, which is an essential requisite to war- inoethyl)-3-aminopropyl-trimethoxysilane) (DAMO)
rant a successful implant performance. based on the co-condensation route. The zwitterionic
⊕
Among bioceramics, silica-based ordered meso- nature of SBA-15 comes from the –NH 3 /–SiO and
Θ
porous materials have been broadly proposed for bone <NH 2 /–SiO zwitterionic pairs present on the ma-
⊕
Θ
tissue regeneration [39–42] . These materials display high terial surface (Figure 1B). In vitro adhesion test with S.
surface areas and pore volumes, tailored and narrow aureus revealed that this zwitterionic bioceramic was
pore size distributions, and functionalizable surfaces. capable of decreasing relative bacterial adhesion from
These characteristics allow these materials to act as 100% (corresponding to pure silica SBA-15) to values
host matrices for a wide range of therapeutic mole- lower than 0.1%. This was the first time that such a
cules, such as drugs, peptides and small proteins, to be huge bacterial inhibition capability was found for a
subsequently released in a sustained fashion at the mesoporous bioceramic at a physiological pH of 7.4.
implantation site [43] . Providing the surface of meso- Moreover, in vitro loading and release assays using
porous matrices of zwitterionic nature to inhibit bac- cephalexin as a model antibiotic demonstrated that
terial adhesion would constitute and add value for the zwitterionic SBA-15 can host drugs into its mesopores,
biomedical application of these materials. Thus, the releasing it in more than 15 days. This finding unlocks
synthesis of zwitterionic SBA-15 type mesoporous outstanding insights into the design of new bone im-
⊕
Θ
material bearing –NH 3 /–COO groups has been re- plants able to play a dual role to treat infections. The
ported (Figure 1B) [44] . This material was synthesized zwitterionic nature allowed inhibiting bacterial adhe-
by the co-condensation method using 3-aminopropyl- sion, i.e., the first stage of implant infection, whereas
triethoxysilane (APTES) and carboxyethyl silanetriol release of antibiotics would help eliminate planktonic
Θ
⊕
sodium salt (CES) silanes as –NH 3 and –COO bacteria in the implant surroundings.
sources respectively, during the synthesis of SBA-15. The above-mentioned results opened up promising
The zwitterionic nature of this material in aqueous expectations in the management and prevention of
medium was conserved at pH values around 5.5, as bone implant infections. However, the great scientific
confirmed by determining its isoelectric point by ζ challenge is providing bioceramics currently in clini-

International Journal of Bioprinting (2016)–Volume 2, Issue 1 23