Theoretical analysis of in vivo macrophage adhesion and foreign body giant cell formation on strained poly(etherurethane urea) elastomers

Abstract

Quantitative description of foreign body giant cell (FBGC) formation on poly(etherurethane urea) (PEUU) surfaces as a function of time can conceivably predict the effects of polymer characteristics on cellular responses in vivo. In the present study, the formation of FBGCs on strained and unstrained PEUUs was quantified with two parameters: the density of adherent macrophages present initially that participate in FBGC formation (d(o)) and the rate constant for cell fusion (k); both kinetic parameters were used to calculate the time-dependent FBGC density (dfc). Relationships were sought between results of the cellular analysis and the extent of environmental stress cracking (ESC), as characterized by scanning electron microscopy. Surface degradation was semiquantified with percent light transmittance. The materials used were: base PEUU, base PEUU with 1% Santowhite antioxidant powder, base PEUU with 5% Methacrol 2138F antifume agent, and base PEUU with both 1% Santowhite and 5% Methacrol 2138F. A comparison of unstrained base PEUU with base PEUU strained to 400% elongation indicated that the rate of cell fusion, but not d(o) and dfc, increased in the presence of strain. In all strained samples, additives that strongly affected the ESC also influenced FBGC kinetic parameters. Strained PEUU containing Santowhite had the lowest d(o), the slowest rate of cell fusion, and lowest dfc, and the least incidence of ESC. The results suggest that the incidence of ESC in PEUU was decreased in the presence of Santowhite, which also lowered the number of adherent macrophages participating in FBGC formation, the rate of FBGC formation and the subsequent FBGC density. These studies also indicate that strain in PEUUs does not directly modulate the adherent macrophage and FBGC density. Further studies are necessary to delineate the relationship between PEUU strain and adherent macrophage and FBGC activation, which leads to the exocytosis of degrading agents and the observed incidence of biodegradation.

In vivo biocompatibility and biostability of modified polyurethanes

“…Implanting procedures reported previously were used. 17 Four samples were implanted for each material at each time point. Empty cages were implanted as controls.…”

“…The casting and test specimen preparation procedures and the straining of tubes have been described previously. 17 In vivo studies were carried out using the cage implant system. The test specimens were placed in stainless steel wire mesh cages.…”

Biocompatibility of poly(etherurethane urea) containing dehydroepiandrosterone

“…Over time, these adherent monocytes differentiate into macrophages, which can then fuse together to form foreignbody giant cells (FBGCs). 3,4 These FBGCs that are present in the long-term foreign-body response can last days, weeks, or even years at the tissue-material interface. [5][6][7] Macrophage adhesion to the surface involves a ligand/receptor binding that activates the cell, resulting in a cell respiratory burst with the production of reactive oxygen intermediates (ROIs) and release of enzymes which can degrade the material.…”

Human monocyte/macrophage adhesion, macrophage motility, and IL-4-induced foreign body giant cell formation on silane-modified surfacesin vitro

“…[13][14][15] The membranes of adherent macrophages have been observed, both in vitro and in vivo, to fuse, resulting in multinucleated FBGC formation. [16][17][18] The molecular mechanisms of macrophage fusion are not well characterized but appear to involve macrophage mannose receptors, LFA-1/ICAM-1 interactions, and transglutaminase activity. [19][20][21][22] Macrophage fusion can be very extensive, producing extremely large FBGCs (>1.0 mm 2 ) that contain hundreds of nuclei.…”