Nanostructured Zirconia Surfaces Regulate Human Gingival Fibroblasts Behavior Through Differential Modulation of Macrophage Polarization

Abstract

Zirconia exhibits excellent biocompatibility and is widely used as dental implant materials in prosthodontics. Over the past years, research and development of dental implant biomaterials has focused on osseointegration, but few reports exist regarding the role of the immune environment on cellular responses to these materials. The present study investigates the effect of different nanostructured zirconia surface topographies on macrophage phenotypes and their influence on gingival fibroblast behavior. Three different nanostructured zirconia surfaces are characterized using scanning electron microscopy, atomic force microscopy, and water contact angle. Blank-machined zirconia (BMZ) surfaces were superior to RAW264.7 cell proliferation and adhesion. RAW264.7 seeded on all nanostructured zirconia surfaces polarized toward both inflammatory M1 and anti-inflammatory M2 macrophages with more M2 macrophage phenotype on BMZ surfaces. Meanwhile, conditioned media (CM) from RAW264.7 culture on three nanostructured zirconia surfaces inhibited cell apoptosis to human gingival fibroblasts (HGFs) but promoted HGF proliferation and secretion. Under modulation of RAW264.7 culture, HGFs cultured on BMZ surfaces significantly secreted more extracellular matrix with a higher expression of collagen-I (COL-I), vinculin (VCL), and fibronectin (FN) than those coated on self-glazed zirconia (CSGZ) and self-glazed zirconia (SGZ) surfaces. After being coated with a nano zirconia film, CSGZ surfaces showed certain changes in cell proliferation, adhesion, and protein production compared with SGZ surfaces. These findings will provide an overview of manipulating surface topography to modulate macrophage phenotypes in order to create an effective macrophage immune response and reinforce soft tissue integration.

Polarized Macrophages in Periodontitis: Characteristics, Function, and Molecular Signaling

“…Wang et al (172) used the antioxidant drug quercetin onto nano-octahedral ceria to inhibit M1 polarization, promote M2 polarization, and the nanocomposites exhibit scavenging of ROS in an animal model of periodontitis. Wu et al (173) were able to modify the behavior of macrophages against gingival fibroblasts by modifying the zirconia surface, providing a new method for restoring periodontal soft tissue attachment after repair therapy. In implant-related studies, Yang et al (174) guided macrophage adhesion by constructing a micro/nanomesh and found that M2 polarization and angiogenesis was promoted.…”

“…Wu et al. ( 173 ) were able to modify the behavior of macrophages against gingival fibroblasts by modifying the zirconia surface, providing a new method for restoring periodontal soft tissue attachment after repair therapy. In implant-related studies, Yang et al.…”

Regulation of Macrophage Polarization on Chiral Potential Distribution of CFO/P(VDF-TrFE) Films

“…In practical applications, the implantation of biomaterials inevitably triggers some immune cell-mediated immune responses, and the immune responses play an important role in releasing pro- or anti-inflammatory factors to regulate angiogenesis and bone formation. − As an immune cell, the phenotype and function of macrophages are capable of polarizing responses to changes in the local physiological microenvironment, thereby maintaining local tissue homeostasis . Macrophages can polarize into pro-inflammatory (M1) and anti-inflammatory (M2) macrophage phenotypes, starting with M1 macrophages by releasing pro-inflammatory factors such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) that trigger initial defensive inflammation, followed by M2 macrophages through the release of anti-inflammatory factors such as the transforming growth factor-β (TGF-β), interleukin-4 (IL-4), and interleukin-10 (IL-10) that induce favorable physiological microenvironments for osteogenesis, improve inflammatory response and secrete factors to promote angiogenesis and bone tissue regeneration, and accelerate the bone regeneration process .…”

Differently Charged P (VDF-TrFE) Membranes Influence Osteogenesis Through Differential Immunomodulatory Function of Macrophages

“…In that, macrophages are recognized as forerunners to discern and respond to foreign biomaterials (Miron and Bosshardt, 2016;Ogle et al, 2016). During the early stages after implantation of biomaterials, the macrophages migrate to the implant area and differentiate into the pro-inflammatory M1 phenotype (classical type), triggering the defensive inflammation by the release of pro-inflammatory molecules, such as interleukin (IL)-1, tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) (Wu et al, 2020). The phenotype plasticity allows macrophages to switch into different phenotypes in response to distinct material signals (Miron and Bosshardt, 2016;Xu et al, 2020).…”