Surface characteristics on commercial dental implants differentially activate macrophages in vitro and in vivo

Abstract

Objectives Biomaterial implantation provokes an inflammatory response that controls integrative fate. M2 macrophages regulate the response to implants by resolving the inflammatory phase and recruiting progenitor cells to aid healing. We have previously shown that modified titanium (Ti) disks directly induce M2 macrophage polarization. The aim of this study was to examine macrophage response to commercially available Ti or Ti alloy implants with comparable roughness and varying hydrophilicity. Material and Methods Eleven commercially available Ti (A‐F) or Ti alloy (G‐K) dental implants were examined in this study. Surface topography, chemistry, and hydrophilicity were characterized for each implant. To compare the immune response in vitro, human monocyte‐derived macrophages were seeded on implants and secreted pro‐ and anti‐inflammatory proteins measured. To evaluate the inflammatory response in vivo, mice were subcutaneously instrumented with clinical implants, and implant adherent macrophage populations were characterized by flow cytometry. Results Macrophages on hydrophobic Implant C produced the highest level of pro‐inflammatory proteins in vitro. In contrast, hydrophilic Implant E produced the second‐highest pro‐inflammatory response. Implants F and K, both hydrophilics, produced the highest anti‐inflammatory protein secretions. Likewise, pro‐inflammatory CD80hi macrophages predominated in vivo on implants C and E, and M2 CD206 + macrophages predominated on implants F and K. Conclusions These findings show that hydrophilicity alone is insufficient to predict the anti‐inflammatory effect on macrophage polarization and that other properties—surface composition or topography—determine immune modulation. This in vivo model may be a useful screening method to compare the immunomodulatory response to clinical implants of disparate geometry or size.

Modulation of immune-inflammatory responses through surface modifications of biomaterials to promote bone healing and regeneration

“…Similarly, pro-inflammatory CD80hi macrophages predominated in vivo in the vicinity of hydrophobic implants, and M2 CD206+ macrophages predominated in the tissue surrounding the hydrophilic implants. 65…”

Macrophagic Inflammatory Response Next to Dental Implants with Different Macro- and Micro-Structure: An In Vitro Study

“…This modification, from phenotypical and functional viewpoints, is defined as "macrophagic polarization" and includes different macrophage subtypes that are able to express a specific set of inflammatory cytokines, and several types of other molecules. Namely, M1 macrophages promote and lead the pro-inflammatory response and produce high levels of IL-1β, IL-6 and TNF-α, in addition to the enzyme NOS, while M2 macrophages are defined as "anti-inflammatory" because they mitigate the pro-inflammatory response during tissue repair and tissue remodeling processes, and they produce high levels of IL-4, IL-10 and TGF-β [7,15,16,18,19].…”

“…A pre-clinical investigation by Abaricia et al [16] also demonstrated that the initial inflammatory response differs between most of the clinical implants analyzed. Changes in surface roughness, chemistry and wettability seem to play a significant role in macrophagic activation and condition the inflammatory microenvironment.…”

“…The authors suggested that a combination of these features direct macrophagic activation. [16] In a recently published paper, we thoroughly described both the chemical composition and the surface topography of five modern commercially available dental implants with different macro-and micro-structures [17]. The present in vitro investigation was intended to measure other surface properties deemed important for the intended clinical purpose of the same five types of dental implants.…”

Classical Dichotomy of Macrophages and Alternative Activation Models Proposed with Technological Progress

“…By changing the characteristics of the implant, the effect of host immune response can be regulated, and then tissue repair can be promoted [ 2 ]. Hotchkiss et al [ 36 , 37 ] have shown that macrophages are particularly important to this response, ultimately driving the conclusion of the inflammatory phase and recruiting mesenchymal stem cells (MSCs) to begin the reparative phase or recruiting other inflammatory cells to delay the healing response [ 38 , 39 ]. In fact, the polarized subtypes of macrophages have no certain advantages and disadvantages to tissue repair; for example, the formation of the vascular network can promote bone tissue regeneration, while the initiation of angiogenesis depends on M1 macrophages, while M2 macrophages play a role in promoting angiogenesis [ 40 – 42 ].…”