Protein and surface effects on monocyte and macrophage adhesion, maturation, and survival.

Cell adhesion and maturation can be affected by the protein adsorption profile on the surface of an implanted biomaterial. In this study we have investigated how surface chemistry and adsorbed proteins can modulate monocyte and macrophage adhesion, IL-13-induced foreign-body giant cell formation, and apoptosis in vitro. Compared to a dimethylsilane-modified surface (DM), a surface modified with RGD peptides had no effect on adhesion density, foreign-body giant cell (FBGC) formation, or apoptosis in nondepleted serum conditions. The depletion of specific adhesive proteins affected adhesion, FBGC formation, and apo- ptosis. While the depletion of fibronectin and vitronectin had no overall effect compared to nondepleted serum conditions, the depletion of IgG from serum caused a significant decrease in initial adherent cell density [1000 +/- 200 compared to 2460 +/- 590 (p = 0.02)], a significant decrease in FBGC formation [2% compared to 17% (p = 0.02)], and a significant increase in the level of apoptosis [57% compared to 32% (p = 0.01)] on DM. The lowered initial adherent cell density on DM was not observed on the RGD surface, indicating that the RGD surface promotes increased initial adhesion. However, the RGD surface does not affect FBGC formation (i.e., macrophage fusion) or levels of apoptosis, which remained comparable to those on the DM surfaces at days 7 and 10.

In vivo biocompatibility and biostability of modified polyurethanes.

Modified segmented polyurethanes were examined for biostability and biocompatibility using an in vivo cage implant system for time intervals of 1, 2, 3, 5, and 10 weeks. Two types of materials were used: polyether polyurethanes and polycarbonate polyurethanes. Two unmodified polyether polyurethanes (PEUU A' and SPU-PRM), one PDMS endcapped polyether polyurethane (SPU-S), and two polycarbonate polyurethanes (SPU-PCU and SPU-C) were investigated in this study. Techniques used to characterize untreated materials were dynamic water contact angle, stress-strain analysis, and gel permeation chromatography. Cellular response was measured by exudate analysis and by macrophage and foreign body giant cell (FBGC) densities. Material characterization, postimplantation, was done by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) in order to quantify biodegradation and scanning electron microscopy (SEM) to qualitatively describe the cellular response and biodegradation. The exudate analysis showed that the acute and chronic inflammatory responses for all materials were similar. Lower FBGC densities and cell coverage on SPU-S were attributed to the hydrophobic surface provided by the PDMS endgroups. The polycarbonate polyurethanes did not show any significant differences in cell coverage or FBGC densities even though the macrophage densities were slightly lower compared to polyether polyurethanes. By 10 weeks, biodegradation in the case of PEUU A' and SPU-PRM was extensive as compared to SPU-S because the PDMS endcaps of SPU-S provided a shield against the oxygen radicals secreted by macrophages and FBGCs and lowered the rate of biodegradation. In the case of polycarbonate polyurethanes, the oxidative stability of the carbonate linkage lowered the rate of biodegradation tremendously as compared to the polyether polyurethanes (including SPU-S). The minor amount of biodegradation seen in polycarbonate polyurethanes at 10 weeks was attributed to hydrolysis of the carbonate linkage.

Protein adsorption on chemically modified surfaces.

Following the implantation of a biomaterial, the first event to occur at the tissue-material interface is protein adsorption. Once proteins have adsorbed to the surface of a material, cells no longer see the material, but only the protein coated surface layer. This adsorbed protein layer can mediate the type of cells that adhere to the surface, which ultimately can determine the type of tissue that develops. In this experiment, glass and polystyrene surfaces were chemically modified forming ionic, non-ionic, hydrophobic, and hydrophilic surfaces. The modified surfaces were incubated in a RPMI diluted serum solution. After incubation, a radioimmunoassay was used to quantify the exposed proteins adsorbed onto the surface of the material. In general, albumin, complement C3 (C3), fibronectin (FN) and vitronectin (VN) competitively adsorbed to the modified surface in a similar fashion, whereas IgG adsorption was the opposite. The hydrophobic surfaces had higher adsorbance of the adhesion proteins (C3, FN and VN) compared to higher adsorption of albumin and IgG onto the hydrophilic surfaces. The surface mobility of the silane modified surfaces also affected the adhesion of proteins. The differences seen in protein adsorption did not directly correlate to monocyte adhesion and Foreign Body Giant Cell (FBGC) development on these surfaces.