Macrophage behavior on multilayered DNA‐coatings in vitro

Abstract

A pivotal factor to consider in the development of biomaterials and biomaterial coatings is the inflammatory response to these materials. The insertion of implants is followed by protein adsorption and subsequent interactions with cellular components of the biological surroundings, in which macrophages play a dominant role through the production of a myriad of signaling molecules. In view of this, the aims of the present study were to evaluate (i) gross protein adsorption to, and (ii) in vitro behavior of macrophages on novel biomaterial coatings, composed of poly-D-lysine (PDL) or poly(allylamine hydrochloride) (PAH) and DNA, and to compare these coatings with negative (noncoated glass) and positive controls (noncoated glass + LPS-stimulation). The results demonstrate that multilayered DNA-coatings do not affect gross protein adsorption compared to noncoated controls. Cell culture experiments showed that the attachment to, and viability and morphology of two types of macrophages cultured on multilayered DNA-coatings is comparable to noncoated controls. Still, macrophages repeatedly showed decreased secretion levels of the proinflammatory cytokine TNF-alpha on multilayered DNA-coatings, whereas no differences were observed in the secretion of IL-1beta, IL-10, and TGF-beta1. Appropriate animal studies are required to elucidate if these in vitro indications have clinical effects on the inflammatory and wound healing processes around implants.

Effect of titanium surface on secretion of IL1β and TGFβ1 by mononuclear cells

“…Though the effects of nano-and microrough titanium topography on osteoblast behavior have been extensively described, [18][19] assays in which monocyte/macrophage behavior is examined are useful determinants for elucidating several aspects of cell interactions with implant biomaterials. 6,11,20 Mononuclear cells, especially monocytes/macrophages, were chosen for this research due to their pivotal role in wound healing, 8 producing a range of molecules which have the potential to modulate the repair process, driving the duration and intensity of the inflammatory response. 20 According to this perspective, it is reasonable to hypothesize that the interaction between mononuclear cells and the implant surface influences the subsequent phases of de novo bone formation.…”

“…6,11,20 Mononuclear cells, especially monocytes/macrophages, were chosen for this research due to their pivotal role in wound healing, 8 producing a range of molecules which have the potential to modulate the repair process, driving the duration and intensity of the inflammatory response. 20 According to this perspective, it is reasonable to hypothesize that the interaction between mononuclear cells and the implant surface influences the subsequent phases of de novo bone formation. 1,21 This assumption stimulated the current research, in which we used single cultures of human mononuclear cells as a biological model.…”

Effects of Titanium Surfaces on the Developmental Profile of Monocytes/Macrophages

“…Thus, it would be reasonable to hypothesize that bio-anodized surfaces induce a Th2 profile. From data obtained in the literature using other cell culture models (7,9), one could infer that the association between surface roughness and the chemical composition of bio-anodized surfaces will induce the release of high amounts of IL10 and TGFβ. However, we do not assume this hypothesis in the present study because the proteins adsorbed by the implant surface may change the way in which the cells adhere onto the biomaterial surface and the way in which the cells are activated (12,14).…”

“…The mediators released by monocyte/macrophage cells can be divided into two major categories: pro-inflammatory, such as interleukin-1 beta (IL1β) (1,2,4,5), tumor necrosis factor alpha (TNFα) (1,(4)(5)(6), and IL6 (1-2,4,5); and antiinflammatory or modulatory, such as IL10 (4)(5)(6)8) and transforming growth factor-beta (TGFβ) (9). This dichotomy established the concept that monocytes/macrophages develop into two major functional types: M1 (classically activated) and M2 (alternatively activated) (10)(11)(12).…”

“…Few studies compare the effects of different titanium surfaces on macrophage activation or consider the role of material surface roughness on protein adsorption (9,15,16). Accumulating evidence suggests that the interactions between macrophages and adsorbed proteins on the material surface provide intracellular signals that are essential for regulating cell function (6,12,14).…”