Characterization of extractable species from poly(etherurethane urea) (PEUU) elastomers.

Methanol extracts of four poly(etherurethane urea) (PEUU) materials were analyzed using Gel Permeation Chromatography (GPC). The additives in the materials were Santowhite powder at 1 wt% and Methacrol 2138 F at 5 wt% loading levels. One-to-two wt% of the original PEUU films was extractable with methanol. The extractables consisted of a low molecular weight (Mw) PEUU polymer, an MDI-rich oligomer, the additives Santowhite (SW) powder and Methacrol 2138 F, and aniline. The low Mw PEUU polymer had a Mw of 12,000 relative to polystyrene, and the MDI-rich oligomer had a Mw of 1000 relative to polystyrene. Quantitation of all extracted species was achieved using GPC; the use of dual-detectors on the GPC made it possible to determine the soft-to-hard composition of the PEUU extracts as a function of molecular weight.

Attachment and proliferation of bovine aortic endothelial cells onto additive modified poly(ether urethane ureas).

To better understand endothelial cell interactions with poly(ether urethane urea) (PEUU) materials, and to assess bovine aortic endothelial cell attachment, films were incubated for 24 h with BAEC in media containing 5% fetal bovine serum. Other films were allowed to incubate for 4 more days in media containing 5% fetal bovine serum without cells to assess BAEC proliferation. The assay was performed on PEUU films modified with acrylate and methacrylate polymer and copolymer additives that spanned a wide range on the hydrophobicity/hydrophilicity scale. Tissue culture polystyrene (TCPS) was used as a control. The assay showed that PEUU films loaded with Methacrol 2138F [copoly(diisopropylaminoethyl methacrylate [DI-PAM]/decyl methacrylate [DM]) (3/1)] or with its hydrophilic component, DIPAM, in homopolymer form (i.e., h-DIPAM), significantly enhanced BAEC attachment (approximately 80% of TCPS values) and proliferation (approximately 80%) when compared to unloaded PEUU films (attachment 73%; proliferation, 47%) or to PEUU films loaded with the more hydrophobic acrylate or methacrylate polymer additives (attachment, 32-69%; proliferation, 18-57%). The assay also showed that PEUU films coated with homopoly(diisopropylaminoethyl acrylate) (h-DIPAA) significantly enhanced BAEC attachment and proliferation when compared to PEUU films coated with h-decyl acrylate (h-DA); films coated with the copolymer of these two acrylates (i.e., co-[DIPAA/DA] [3/1]) showed intermediate behavior. To explain the enhancement of BAEC interaction with films loaded with Methacrol 2138F or h-DIPAM, when compared to unmodified PEUU films or to PEUU films loaded with more hydrophobic acrylate and methacrylate polymer additives, it was assumed that the additives near the surface region of the solvent swollen PEUU matrix may have migrated to, or near to, the PEUU-air interface during film formation, creating an additive enriched PEUU surface region. It is suggested that, once at this surface region, dynamic reorientation in response to an aqueous medium ensured the additives were able significantly to influence protein adsorption, and concomitant endothelial cell behavior, but only if they interacted with aqueous media more favorably than the PEUU. The ability of Methacrol and h-DIPAM additives to enhance endothelial cell behavior is argued to be the result of increased hydrophilicity. This is the result of exposed, hydrogen-bonding DIPAM moieties and increased surface flexibility, which is itself due to the hydration of unhindered Methacrol chains, which may create an additive enriched PEUU-water interfacial zone.

Protein adsorption to poly(ether urethane ureas) modified with acrylate and methacrylate polymer and copolymer additives.

To understand better blood interactions with poly(ether urethane urea) (PEUU) materials, a radioimmunoassay and whole or diluted human plasma were used to characterize the presence of fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin on a PEUU formulation and on PEUU formulations modified with the amphiphilic additive Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate] [3/1]), or with hydrophobic acrylate or methacrylate polymer or copolymer additives. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F (Methacrol) or homopoly-DIPAM (h-DIPAM) adsorbed significantly lower amounts of the studied proteins than did either the base PEUU formulations or the PEUUs loaded with the more hydrophobic acrylate or methacrylate polymer additives. Experiments with Methacrol-loaded PEUUs, where the loading of Methacrol was varied from 0.25 wt% to 20.0 wt%, showed that the adsorption of each of the characterized proteins did not vary significantly throughout the Methacrol loading range, and that all Methacrol-loaded PEUU formulations adsorbed significantly lower amounts of the studied proteins than did the unloaded PEUU. Phase separation within the additive loaded PEUUs was characterized by scanning electron microscopy (SEM). The solubility parameters of the additives, as well as of the base PEUU, were calculated and used to interpret differences in phase separation of the additive modified PEUUs. The analysis showed that additives of lower solubility parameter phase-separated into fewer large microdroplets within the PEUU matrix. SEM analysis also showed that additive microdroplets were not present on the air side surface of loaded PEUUs. To explain the differences in protein adsorption to the air side of additive loaded PEUUs when compared to the base PEUU, it was assumed that the additives near this region of the solvent swollen PEUU matrix may have migrated to, at, or near the PEUU-air interface during film formation, creating an additive enriched PEUU surface region. Once at this surface region, it was suggested that dynamic surface reorientation in response to an aqueous medium ensured that the additives were able significantly to influence protein adsorption behavior only if they interacted with aqueous media more favorably than the PEUU.

Protein adsorption onto poly(ether urethane ureas) containing Methacrol 2138F: a surface-active amphiphilic additive.

Surface characterization and protein adsorption studies were carried out on a series of additive dispersed and additive coated poly(ether urethane ureas), PEUUs, to characterize early events in the blood compatibility of these materials. A hypothesis that is based on surface hydrophilicity, surface flexibility, and adsorption media has been developed to understand the modulated adsorption of plasma proteins by PEUU additives. Electron spectroscopy for chemical analysis (ESCA) and contact angle analysis were performed on two PEUU formulation as well as on PEUU formulations modified with Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate (DM)][3/1]) or acrylate or methacrylate polymer or copolymer analogs of Methacrol 2138F. Methacrol 2138F is a commercially used amphiphilic copolymethacrylate. ESCA showed that the PEUUs loaded with Methacrol 2138F or with its hydrophilic component, homopoly (DIPAM) (h-(DIPAM)), had a higher percentage of nitrogen at their surfaces than did the base PEUUs. Contact angle analysis also showed that the air side of PEUU formulations loaded with Methacrol 2138F were more hydrophobic than was the air side of base PEUUs when films were cast from dimethylacetamide. However, during contact angle testing, the air side of PEUU films loaded with Methacrol 2138F rapidly became more hydrophilic than did the air side of the base PEUU films. A radioimmunoassay and whole or diluted human plasma were also used to characterize the presence of the proteins fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin, on the surface of the same PEUUs as analyzed by ESCA and contact angle. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F, with a copolyacrylate analog of Methacrol 2138F (co(diisopropylaminoethyl acrylate [DIPAA]/decyl acrylate [DA]) [3/1]), or with the hydrophilic polyacrylate or polymethacrylate component analogs of Methacrol 2138F (h-DIPAM or h-DIPAA) adsorbed significantly lower amounts of the proteins than did either the base PEUU formulations or the homopoly(decyl methacrylate) (h-DM) or homopoly(decyl acrylate) (h-DA) coated or loaded PEUUs.

Infrared spectral analysis of extractables from poly(etherurethane urea) (PEUU) elastomers.

Poly(etherurethane urea) (PEUU) elastomers when employed as biomedical devices may be susceptible to extraction upon implantation. Four PEUU elastomers containing a single PEUU formulation, but varying in terms of their additives, were subjected to an in vitro extraction procedure. The additives in the PEUUs were Methacrol 2138 F at 5 wt% and Santowhite powder at 1 wt% levels. Only 1-2 wt% of the PEUUs was extractable with methanol. Fourier transform infrared spectroscopy (FT-IR) furnished qualitative and quantitative information on the extractables. The extractables consisted of a PEUU component that on the average was richer in soft segment than the bulk PEUU, and the two additives, Methacrol 2138 F and Santowhite powder.

Theoretical analysis on cell size distribution and kinetics of foreign-body giant cell formation in vivo on polyurethane elastomers.

The nature of in vivo leukocyte adhesion and foreign-body giant cell (FBGC) formation on polyurethanes was studied through theoretical and statistical analyses in terms of cell size distribution, density changes, and kinetics of FBGC formation. The results showed that the size distribution of FBGCs followed a "most probable" distribution. During FBGC formation, the densities of FBGCs changed with time. At an early stage, the number of FBGCs increased with time to a maximum at the expense of macrophages. As more FBGCs were formed and less macrophages were present, the fusion of FBGCs among themselves became significant. This, in turn, caused a gradual decrease of FBGC density with time. The rate of FBGC formation was characterized by a rate constant that represented certain characteristics of cell fusion and FBGC formation and the density of initial FBGC-forming macrophages that were a small fraction of leukocytes adhering to the surface. The direct correlations of surface cracking and pitting and adherent FBGCs demonstrated the influence of phagocytic actions of FBGCs on the biostability of implanted polyurethanes. While the cracking was thought to be caused by oxidative degradation facilitated by oxygen ion/radical release of FBGCs, the pitting appeared to result from the Methacrol 2138F aggregates diffusing out of the polymer in an acidic microenvironment under FBGCs, which in turn could be enhanced by the surface degradation and cell phagocytosis. The added Santowhite powder in polyurethane had a significant influence on FBGC formation: It reduced FBGC density and rate of FBGC formation by reducing leukocyte adhesion and the number of macrophages participating in FBGC formation.

Effect of some additives on the biostability of a poly(etherurethane) elastomer.

Four materials based on a single poly-(etherurethane) (PEU) prepared from MDI and PTMEG but differing in additives were studied in the cage implant system. The two additives studied were Santowhite powder at the 1% level and Methacrol 2138F 5%. Methacrol 2138F appeared to be immiscible with the base PEU and was dispersed in discrete domains about 0.5-micron in size. The retrieved PEU specimens were also cleaned and examined in the optical and scanning electron microscopes, and the size and density of adherent foreign body giant cells (FBGCs) were measured at implantation times up to 10 weeks. Methacrol 2138F had no effect on the density, coverage or size distribution of adherent FBGCs, but leaching of Methacrol 2138F was considered to be responsible for extensive pitting of the PEU surface. On the other hand, Santowhite powder appeared to inhibit formation of FBGCs, and while surface cracking and flaking were observed as early as 3 weeks postimplantation on some PEUs, the Santowhite powder effectively inhibited surface cracking and flaking up to the longest implantation time studied.