Modulating macrophage polarization on titanium implant surface by poly(dopamine)‐assisted immobilization of IL4

Abstract

Background In the past few decades, very little research has been carried out to modify implant surfaces to improve osteointegration through the regulation of immune cells. Purpose The aim of this study is to investigate whether the poly(dopamine) (pDA)‐assisted immobilization of IL4 on titanium surfaces could modulate the inflammatory profile of macrophages in vitro and search for the possibility of enhancing implant integration in this way. Material and Methods The surface composition, topography, and roughness of SLA, SLA‐pDA, and SLA‐pDA‐IL4 discs were examined by scanning electron microscope (SEM) and energy dispersive spectrometer (EDS). Then the releasing profile of the SLA‐pDA‐IL4 implants was recorded for 1 week and the bioactivity of released IL4 was investigated by ELISA. Then macrophage polarization was investigated via three methods including: (a) surface marker via immunofluorescence; (b) mRNA levels of M1 and M2 polarization markers via real‐time PCR, and (c) cytokine release via ELISA. Results SEM and EDS revealed that pDA and IL4 were coated successfully on SLA surfaces. The ELISA results showed that IL4 remained its bioactivity on SLA surface and were immobilized on the SLA surface. The immobilization of IL4 through pDA has no significant influence on the attachment, morphology, and proliferation of macrophages, while it increased the M2/M1 proportion in human macrophages revealed by immunofluorescence. The real‐time PCR and ELISA results demonstrated that SLA‐pDA‐IL4 surface reduced the pro‐inflammatory profile compared with SLA‐pDA and SLA surfaces. Conclusions The SLA‐pDA‐IL4 surfaces described here is able to activate adherent macrophages into M2 phenotype and reduce the release of pro‐inflammatory cytokines. Immobilization of IL4 via pDA is convenient and effective, thus providing an applicable way to control macrophage behavior upon implant insertion and is anticipated to accelerating further bone integration.

Polydopamine-Decorated Microcomposites Promote Functional Recovery of an Injured Spinal Cord by Inhibiting Neuroinflammation

“…These decreases of cytokines could be attributed to the rapid release of MP from MP-PLGA. Similarly, benefiting from the excellent adhesive nature of the PDA layer, − PLGA@PDA significantly ( P < 0.05) reduced the level of TNF-α, IL-6, and IL-10 by 45.8, 38.5, and 40.1%, respectively, of the corresponding cytokine level in the PBS group at 12 h after administration (Figure h). Meanwhile, the reduction of cytokines in the MP-PLGA or PLGA@PDA group increased as the incubation time extended from 0 to 72 h. Until the end of this study (72 h after administration), PLGA@PDA caused a decrease of 58.8, 45.7, and 49.7% in TNF-α, IL-6, and IL-10, respectively.…”

3D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis

“…Previous studies reported that IL4 promoted M2 macrophage polarization in several materials. 11 , 15 , 16 The innovation of our study lies, first, in the difference in material modification; we used 3D printing technology, which is more conducive to clinical use, especially in cases of acetabular fracture. Different morphologies have different impact mechanisms and effects on immune cells and osteoblasts; therefore, the specificity of the material is explained based on the morphological characteristics.…”

“… 15 Immobilization of IL4 using polydopamine is convenient and effective for controlling macrophage behaviour upon implant insertion, further accelerating bone integration. 16 IL4 drives the transition of macrophages to pro‐healing M2 in vitro and in vivo, 11 and this has been linked to enhanced osteogenic and angiogenic properties of these materials. It has been reported that the delivery of IL4 significantly enhanced decellularized bone matrix-mediated osteogenesis and angiogenesis via the coordinated involvement of M1 and M2.…”

Osseointegration—the biological reality of successful dental implant therapy: a narrative review

“…For example, PTH administration increased bone formation at titanium implants in an osteoporotic rabbit model ( 56) and increased early bone formation at implants in an aging rat model (57). The treatment of titanium implant surfaces with IL-4, a cytokine the promoted M2 (pro-regenerative) macrophage polarization and reduce pro-inflammatory cytokine production by adherent cells (58). Blocking the inhibitory action of sclerostin by linking sclerostin-neutralizing antibodies to titanium implant surfaces promoted greater osseointegration (32).…”