Hydrophilic titanium surface‐induced macrophage modulation promotes pro‐osteogenic signalling

Hamlet, Stephen; Lee, Ryan S. B.; Moon, Hojin; Alfarsi, Mohammed A; Ivanovski, Sašo

doi:10.1111/clr.13522

Cited by 55 publications

(46 citation statements)

References 45 publications

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“…To mediate a desirable transition from inflammation to healing, macrophage populations at an injury or implantation site shift from a pro‐inflammatory (M1) phenotype into an anti‐inflammatory (M2) phenotype. We and others have demonstrated that macrophage activation in response to biomaterial surface modifications in vitro is predictive of macrophage activation, inflammation resolution, and MSC recruitment in vivo (Donos et al., 2011; Hamlet et al., 2019; Hotchkiss et al., 2016; Hotchkiss et al., 2017; Hotchkiss et al., 2018; Wang et al, 2019a).…”

Section: Introductionmentioning

confidence: 92%

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

Abaricia

Shah

Ruzga

et al. 2021

Clinical Oral Implants Res

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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.

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Section: Introductionmentioning

confidence: 92%

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

Abaricia

Shah

Ruzga

et al. 2021

Clinical Oral Implants Res

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“…No alternations in surface roughness and topography may lead to the effect that no significant differences in water contact angle of differently charged P (VDF-TrFE) surfaces. Therefore, the interference of the topography and wettability of biomaterials with the behavior of macrophages reported in numerous studies (Hotchkiss et al, 2016;Hamlet et al, 2019) were excluded in this work. Combining surface-potential results to analyze, the three P (VDF-TrFE) membranes with similar surface topography and wettability but different surface charge polarity, such as negatively (poled -), positively (poled +) and neutrally (nonpoled) charged P (VDF-TrFE) membranes, were fabricated in this study.…”

Section: Macrophage Adhesion and Morphology Affected By The Surface-charge Polarity Of P (Vdf-trfe) Membranesmentioning

confidence: 99%

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

et al. 2022

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A biomaterial-mediated immune response is a critical factor to determine the cell fate as well as the tissue-regenerative outcome. Although piezoelectric-membranes have attracted considerable interest in the field of guided bone regeneration thanks to their biomimetic electroactivity, the influence of their different surface-charge polarities on the immune-osteogenic microenvironment remains obscure. The present study aimed at investigating the interaction between piezoelectric poly (vinylidene fluoridetrifluoroethylene) [P (VDF-TrFE)] membranes with different surface polarities (negative or positive) and macrophage response, as well as their subsequent influence on osteogenesis from an immunomodulating perspective. Specifically, the morphology, wettability, crystal phase, piezoelectric performance, and surface potential of the synthetic P (VDF-TrFE) samples were systematically characterized. In addition, RAW 264.7 macrophages were seeded onto differently charged P (VDF-TrFE) surfaces, and the culture supernatants were used to supplement cultures of rat bone marrow mesenchymal stem cells (rBMSCs) on the corresponding P (VDF-TrFE) surfaces. Our results revealed that oppositely charged surfaces had different abilities in modulating the macrophage-immune-osteogenic microenvironment. Negatively charged P (VDF-TrFE), characterized by the highest macrophage elongation effect, induced a switch in the phenotype of macrophages from M0 (inactivated) to M2 (anti-inflammatory), thus promoting the osteogenic differentiation of rBMSCs by releasing anti-inflammatory cytokine IL-10. Interestingly, positively charged P (VDF-TrFE) possessed pro-inflammatory properties to induce an M1 (pro-inflammatory) macrophage-dominated reaction, without compromising the subsequent osteogenesis as expected. In conclusion, these findings highlighted the distinct modulatory effect of piezoelectric-P (VDF-TrFE) membranes on the macrophage phenotype, inflammatory reaction, and consequent immune-osteogenic microenvironment depending on their surface-charge polarity. This study provides significant insight into the design of effective immunoregulatory materials for the guided bone regeneration application.

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“…On the other hand, Alfarsi et al [157] reported that surface hydrophilic modifications downregulated the gene expression profiles of several pro-inflammatory cytokines and of their associated proteins. Hamlet et al [158] investigated the comparative effect of two hydrophilic modified sandblasted/acid-etched (modSLA) and SLA Ti surfaces and the results showed a reduction in the gene expression profiles of the TNF-α, IL-1β, IL-1α cytokines and MCP-1 chemokine from the macrophages seeded on the surface of the hydrophilic Ti. In another study, Dai et al [159] evaluated the effect of hydrophilic Ti disks on RAW 264.7 murine macrophages and the results obtained revealed that the hydrophilic surface was able to upregulate the secretion of IL-10 and downregulate the secretion TNF-α, respectively.…”

Section: Surface Chemistry Alterationsmentioning

confidence: 99%

“…These observations suggested that microroughness could be beneficial for the healing and bone regeneration processes. However, Hamlet et al [ 158 ] reported contradictory results, demonstrating that Ti substrates with modified microroughness promoted an enhanced pro-inflammatory cytokine profile.…”

Section: Development Of Bone Biomaterials With Immunomodulatory Prmentioning

confidence: 99%

The State of the Art and Prospects for Osteoimmunomodulatory Biomaterials

Negrescu

Cîmpean

2021

Materials

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The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory properties, a desired immune response can be triggered in order to obtain a proper bone regeneration process. In this context, various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells. The current review provides an overview of recent developments in such applied strategies.

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Hydrophilic titanium surface‐induced macrophage modulation promotes pro‐osteogenic signalling

Cited by 55 publications

References 45 publications

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

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

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

The State of the Art and Prospects for Osteoimmunomodulatory Biomaterials

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