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International Journal of Bioprinting 3D printed PEEK scaffold mediates macrophages to affect osseointegration

into the body as a foreign body, the immune system is Poly(ether-ether-ketone) (PEEK), as a semi-crystalline,
first activated, and then a large number of cytokines and non-absorbable thermoplastic material with stable
signaling protein molecules are released in response to chemical properties, excellent mechanical properties,
the changes in the immune microenvironment around and low friction properties, is considered one of the most
the bone repair material [3-5] . As an important part of the promising orthopedic implant materials [20-22] . However,
immune system, macrophages play an important role in as an “inert” material, the poor biocompatibility and
angiogenesis and bone regeneration during bone repair [6-8] . osseointegration properties of PEEK limit its wide clinical
The phenotypic transition of macrophages is dynamic and application [15,23-25] . Based on the sensitivity of phenotypic
plastic, and can be divided into M1 and M2 macrophages polarization of macrophages to material pore size and
according to the immune response of the surrounding the role of macrophages in mediating osseointegration,
microenvironment [9,10] . Classical M1 macrophages are we believe that regulating macrophage polarization by
generally considered pro-inflammatory cells that secrete changing the pore size of PEEK scaffold can enhance
tumor necrosis factor (TNF)-α and interleukin (IL)-1β bone integration between PEEK scaffold and host bone,
cytokines to accelerate the progression of inflammation. and finally promote the rapid repair of bone defects. To
M2 macrophages are considered anti-inflammatory cells test this hypothesis, we constructed three-dimensional
that release tissue repair factors, such as TNF-β, bone (3D)-printed PEEK scaffolds with pore sizes of 0, 200,
morphogenetic protein-2 (BMP-2), vascular endothelial and 400 μm, and used in vitro and in vivo experiments to
growth factor (VEGF), and platelet-derived growth factor investigate the effect of scaffold pore size on macrophage
BB (PDGF-bb), which can promote vascularization, polarization and subsequent angiogenesis and osteogenesis.
osteogenic differentiation, and tissue repair [11-13] . In recent The macrophage response to PEEK scaffold pore size and
years, several studies have used bone repair materials to the potential relationship between scaffold pore size,
load ions and cytokines with immunomodulatory effects macrophage function, and osseointegration were further
to achieve the regulation of macrophage phenotype explored, hoping to provide new insights into promoting
polarization and promote the osteogenic differentiation of osseointegration of PEEK bone repair materials.
stem cells and the healing of bone defects, which further
confirms the role of macrophages in bone defect repair [14-16] . 2. Material and methods
Therefore, bone repair materials with immunomodulatory
effects should have the effect of inducing phenotypic 2.1. Preparation of 3D-printed PEEK scaffolds
polarization of macrophages, thereby establishing a Powdered medical PEEK raw materials were prepared into
microenvironment that enhances osteogenesis. filaments with a diameter of 1.75 mm, and then PEEK
scaffolds (printing temperature = 420°C, nozzle diameter =
Studies have shown that the pore structure of 400 μm, layer height = 400 μm, scaffold diameter = 8 mm,
materials plays an indispensable role in regulating the scaffold thickness = 3 or 10 mm) with different pore sizes
polarization phenotype of macrophages. Garg et al. found were printed by FDM 3D printer (JUGAO-AM, Surgeon
that increasing the pore size of electrospun scaffolds from Plus, China), and the scaffolds with pore sizes of 0, 200,
1.92 to 29.46 μm induces polarization of macrophages and 400 μm were named PEEK0, PEEK200, and PEEK400,
toward the M2 phenotype . Luu et al. found that the respectively. In order to increase the hydrophilicity of PEEK
[17]
morphology and polarization state of macrophages can scaffolds, the PEEK scaffolds were washed in deionized
be changed by using the surface topology changes of water, ethanol, and acetone in turn, and then the PEEK
materials, and the micro-nano grooves can promote scaffolds were immersed in concentrated sulfuric acid
the growth of macrophages and the polarization of for 15 s, and then immersed in concentrated nitric acid
macrophages to M2 phenotype . The scaffold pore size at 70°C for 30 min [15,26] . After ultrasonic cleaning (three
[18]
can affect the polarization phenotype of macrophages, and times, 20 min each time), the samples were soaked in
scaffolds with large pore sizes showed greater potential deionized water for 24 h to remove excess acid, and finally
in promoting M1-to-M2-type polarization . Sussman 3D-printed hydrophilized-PEEK scaffolds with different
[18]
et al. found that macrophages in scaffolds with an average pore sizes were obtained.
pore size of 160 μm tended to express higher levels of the
M2 marker compared to scaffolds with an average pore 2.2. Characterization of 3D-printed PEEK scaffolds
size of 34 μm . Previous studies have shown that the 2.2.1. Scanning electron microscopy (SEM)
[19]
phenotypic polarization of macrophages is sensitive to All samples were sputter-coated with an Ion Sputter (E-
the pore size of the material, so it is feasible to modulate 1010, Hitachi, Tokyo, Japan), and the morphology was
the phenotype of macrophages by designing the pore size observed by scanning electron microscope (SEM, S2400,
of the material. Hitachi).

Volume 9 Issue 5 (2023) 129 https://doi.org/10.18063/ijb.755