Characterization of Macrophage and Cytokine Interactions with Biomaterials Used in Negative-Pressure Wound Therapy

Abstract

Macrophages are innate immune cells that help wounds heal. Here, we study the potential immunomodulatory effects of negative-pressure wound therapy (NPWT) materials on the macrophage inflammatory response. We compared the effects of two materials, Granufoam™ (GF) and Veraflo Cleanse™ (VC), on macrophage function in vitro. We find that both materials cause reduced expression of inflammatory genes, such as TNF and IL1B, in human macrophages stimulated with bacterial lipopolysaccharide (LPS) and interferon-gamma (IFNγ). Relative to adherent glass control surfaces, VC discourages macrophage adhesion and spreading, and may potentially sequester LPS/IFNγ and cytokines that the cells produce. GF, on the other hand, was less suppressive of inflammation, supported macrophage adhesion and spreading better than VC, and sequestered lesser quantities of LPS/IFNγ in comparison to VC. The control dressing material cotton gauze (CT) was also immunosuppressive, capable of TNF-α retention and LPS/IFNγ sequestration. Our findings suggest that NPWT material interactions with cells, as well as soluble factors including cytokines and LPS, can modulate the immune response, independent of vacuum application. We have also established methodological strategies for studying NPWT materials and reveal the potential utility of cell-based in vitro studies for elucidating biological effects of NPWT materials.

Modulation of Stiffness-Dependent Macrophage Inflammatory Responses by Collagen Deposition

“…We observed increased cell spreading on Col-AA compared to that in Col-HEP-conjugated surfaces, likely due to enhanced integrin-mediated focal adhesion (Figure C). These findings were in line with earlier observations wherein the focal adhesion protein vinculin was found to stabilize adhesion receptors, promote cell spreading, and transmit force at cell–cell and cell–matrix junctions. , In addition, macrophage adhesion to its substrate is an important determinant of its inflammatory activation as our work has shown that short durations of adhesion or adhesion to ultralow binding surfaces significantly suppresses inflammatory activation. , Increased cell spreading in Col-AA may have caused enhanced adhesion and translocation of YAP/TAZ into the nucleus, resulting in higher secretion of inflammatory cytokines. In addition, the fibrillar structure of Col-HEP-conjugated surfaces may discourage optimal cell–matrix adhesion and cell spreading, likely due to limited interactions with focal adhesions while promoting engagement of inhibitory receptor LAIR-1 with its ligands in the collagen; together, these effects could lead to suppressed inflammatory activation.…”

“… 52 , 53 In addition, macrophage adhesion to its substrate is an important determinant of its inflammatory activation as our work has shown that short durations of adhesion or adhesion to ultralow binding surfaces significantly suppresses inflammatory activation. 17 , 54 Increased cell spreading in Col-AA may have caused enhanced adhesion and translocation of YAP/TAZ into the nucleus, resulting in higher secretion of inflammatory cytokines. In addition, the fibrillar structure of Col-HEP-conjugated surfaces may discourage optimal cell–matrix adhesion and cell spreading, likely due to limited interactions with focal adhesions while promoting engagement of inhibitory receptor LAIR-1 with its ligands in the collagen; together, these effects could lead to suppressed inflammatory activation.…”

PDMS Micropatterns Coated with PDA and RGD Induce a Regulatory Macrophage-like Phenotype

“…Previous studies have demonstrated that Mreg/anti-inflammatory macrophages exhibit elongated morphology and cells express M2 phenotype markers even in the absence of exogenous stimuli [ 11 , 30 ]. Therefore, we first examined the cell morphology and the degree of cell elongation by microscopy.…”

Cell-Tissue Interaction: The Biomimetic Approach to Design Tissue Engineered Biomaterials

“…Thanks to the recent progress registered in the fields of materials science and TE, it is possible to modulate the physicochemical and biological properties to generate a biobased scaffold for various applications, from antibacterial surfaces [60] and engineered bacteria [61] to tissue regeneration [62][63][64][65][66] and wound healing [17,67,68]. Particularly, cellbiomaterial interactions are crucial to determine the cellular fate in terms of adhesion [69,70], proliferation [71], differentiation [72,73], morphology [74,75], migration [76,77], and for the ECM-mimetic scaffold fabrication [78,79].…”