Page 301 - IJB-9-2

International Journal of Bioprinting Zn-doped coatings with osteogenic and antibacterial properties

1. Introduction and bioabsorbability [27,28] . The positively charged amino
group in chitosan can generate electrostatic interaction with
Skeleton supports human body and protects other vulnerable the negatively charged carboxyl group in sodium alginate.
internal organs, and plays a key role in blood production Therefore, multilayer polymer coatings can be constructed
and mineral storage [1-3] . To ensure a healthy skeletal system, by layer-by-layer method [29,30] . Besides, sodium alginate can
bones are in a constant process of remodeling to adjust to be crosslinked with divalent metal ions to gelation, and the
mechanical injuries and tiny lesions. However, once the metal ions are stably loaded into the multilayer coatings .
[31]
bone defects exceed the critical size that the bone can no
longer repair itself, bone substitutes would be needed for In this study, porous hydroxyapatite (HA) bioceramic
healing purposes [4,5] . Since the traditional bone substitutes, scaffolds was prepared by digital light processing (DLP)
including autologous bone and allogeneic bone, were method, and chitosan/sodium alginate polymer coatings
unable to fulfill therapeutic requirements, synthetic bone were added to scaffolds by layer-by-layer method. Next,
2+
substitutes have gradually become the focus of research . Zn ions were doped where the ion concentrations were
[6]
Calcium phosphate (CaP) bioceramics were one of the changed layer by layer to achieve a stable and controllable
earliest bone repair materials in relevant researches release. Finally, the balance between antimicrobial
because of its biocompatibility and osteoblastic induction properties and biological properties was achieved.
properties [7-9] . Nonetheless, pure CaP bioceramics showed
poor mechanical and antimicrobial properties, which can 2. Materials and methods
be improved by modification [10,11] . 2.1. Preparation of porous scaffolds
In view of the increase of bone transplant failure The detailed preparation process of HA porous scaffolds
cases caused by infection every year, antimicrobial is described as follows. The first step was to prepare the
property has become one of the most desired properties slurry. HA powders (Aladdin, China) and photosensitive
of bone substitutes [12,13] . Furthermore, due to the misuse resin (Shanghai, China) were mixed at a mass ratio of
of antibiotics for years, drug-resistant bacteria have also 1:1.1, with 3 wt.% of dispersant (Shanghai, China). All
become another challenge [14,15] . Metal ions such as Ag , raw materials were put into a vacuum disperser, and the
+
Zn , and Cu have shown the ability to kill bacteria and slurry was obtained after stirring at 1100 rpm for 30 min.
2+
2+
are unlikely to cause mutations in pathogenic bacteria [16,17] . Next, a self-developed DLP printer was used to fabricate
Therefore, the doping of appropriate content of metal the green bodies. The porous scaffold model was designed
elements to scaffolds to kill bacteria in situ became using Magics 23.0 software (the average pore size was
the most adopted antibacterial strategy at present. In ~1000 μm). According to the experimental requirements,
particular, it has been proven that Zn ions not only the larger cuboid scaffolds (9 × 9 × 13.5 mm ) were
2+
3
possessed reliable antibacterial activity, but also could prepared for mechanical test, the smaller cuboid scaffolds
promote osteoblastogenesis [18,19] . However, once the release (9 × 9 × 4.5 mm ) were prepared for biological test, and the
3
rate of Zn ions exceeds the safety limits, the scaffolds cylindrical scaffolds (Ф4.5 × 4.5 mm ) were prepared for
2+
3
will become toxic to normal cells such as osteocyte . inhibition zone test. After washing and drying, the ceramic
[20]
Some researchers gave priority to osteogenic activity at green bodies were debinded and sintered at 1500°C for 3 h;
the expense of antibacterial effect [21,22] . The others studied detailed temperature curves were shown in the previous
the addition of other substances to offset the cytotoxicity research . The fabrication process is shown in Figure 1.
[32]
of Zn 2+[23,24] . Considering the fact that the perioperative
period is associated with high incidence of infection [25,26] , 2.2. Preparation of coatings
initial antibacterial property is more important than long- The chitosan (Aladdin, China) was dissolved in 0.2% acetic
term antibacterial property. On that basis, a balanced acid (Aladdin, China) solution with the concentration
strategy is proposed in this paper, which is to control the of 2 g/L. The sodium alginate (Aladdin, China) was
release rate of Zn from scaffolds by preparing coatings dissolved in deionized water with the concentration of
2+
with different Zn contents layer by layer, so as to increase 2 g/L. Meanwhile, four different crosslinking solutions
2+
the killing rate of bacteria in the initial stage after implant containing increasing concentrations of ZnCl solution
2
surgery and to strengthen the osteogenic property in the (0, 0.25, 0.5, and 1 g/L) were prepared, and CaCl of
later stage. Moreover, to obtain such multilayer coating, variable concentration was added to adjust the total metal
2
polymer is chosen as the most appropriate material. ion concentration to 2 g/L. Subsequently, the HA scaffolds
Chitosan and sodium alginate, as biodegradable natural were immersed in the alginate solution, chitosan solution,
polymers, have been widely developed in bone tissue and one kind of crosslinking solution for 5 min. After each
engineering domains due to outstanding biocompatibility soaking process, the scaffolds were cleaned with distilled

Volume 9 Issue 2 (2023) 293 https://doi.org/10.18063/ijb.v9i2.668