Comparative stability of the bioresorbable ferric crosslinked hyaluronic acid adhesion prevention solutions.

The Intergel® ferric crosslinked hyaluronate (FeHA) adhesion prevention solution (APS) (FDA) is associated with serious post-operative complications (Henley, http://www.lawyersandsettlements.com/features/gynecare-intergel/intergel-timeline.html, 2007; FDA, 2003; Roman et al., Fertil Steril 2005, 83 Suppl 1:1113-1118; Tang et al., Ann Surg 2006;243(4):449-455; Wiseman, Fertil Steril 2006;86(3):771; Wiseman, Fertil Steril 2006;85(4):e7). This prompted us to examine the in situ stability of crosslinked HA materials to hyaluronidase lyase degradation. Variables such as ferric ionic crosslink density, HA concentration, gel geometry, and molecular weight (MW) of HA polymer were studied. Various formulations of the crosslinked "in house" [Isayeva et al., J Biomed Mater Res: Part B - Appl Biomater 2010, 95B (1):9-18] FeHA (0.5%, w/v; 30, 50, 90% crosslinked), the Intergel® FeHA (0.5%, w/v; 90%), and the non-crosslinked HA (0.05-0.5%, w/v) were degraded at a fixed activity of hyaluronidase lyase from Streptomyces hyalurolyticus (Hyase) at 37°C over time according to the method [Payan et al., J Chrom B: Biomed Sci Appl 1991;566(1):9-18]. Under our conditions, the data show that the crosslink density affects degradation the most, followed by HA concentration and then gel geometry. We found that MW has no effect. Our results are one possible explanation of the observations that the Intergel® FeHA APS (0.5%, w/v; 90%) material persisted an order of magnitude longer than expected [t1/2 = 500 hrs vs. t1/2 = 50 hrs (FDA; Johns et al., Fertil Steril 1997;68(1):37-42)]. These data also demonstrate the sensitivity of the in vitro hyaluronidase assay to predict the in situ stability of crosslinked HA medical products as previously reported [Sall et al., Polym Degrad Stabil 2007;92(5):915-919].

Determination of total leachable bisphenol A from polysulfone membranes based on multiple consecutive extractions.

The paper presents the development of a multiple consecutive extraction method enabling the determination of the total amount of bisphenol A (BPA) released from porous polysulfone (PS) membranes in a hemodialyzer or hemoconcentrator under simulated-use conditions. The levels of BPA were determined using solid phase extraction (SPE) coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS). We demonstrated that it was difficult to determine the total amount of BPA released from the PS membranes using a single extraction method with finite solvent volume because of the chemical equilibrium between the extraction solution and the polymer phase. Repeated extractions gave more accurate results than a single extraction for the determination of the total amount of leachables in porous membranes. A general equation was derived to fit the elution profile of BPA released during multiple consecutive extractions.

Contamination of ultrapure water with bisphenol A leached from polysulfone ultrafilter.

Ultrapure water produced by a water purification system is one of the most essential and widely used reagents in laboratories. However, its quality is usually the least well-characterized and often overlooked. Here we investigate the contamination of ultrapure water by bisphenol A (BPA) leached from a polysulfone (PS) ultrafilter in a water purification system. To evaluate the level of BPA in ultrapure water, we used an offline solid-phase extraction (SPE) coupled with liquid chromatography mass spectrometry (LC-MS). Initial BPA level leached from a new PS ultrafilter was 0.70±0.06 ng/mL. The concentration of BPA decreased gradually with continuous dispensation of purified water and was 0.20±0.02 ng/mL at 33.5-L dispensation. The total amount of extractable BPA was 64.4±1.4 µg per PS ultrafilter. The cumulative amount of BPA leached during dispensation of 33.5-L water was 1.2±0.1 µg, which only accounts for 2% of the total amount of extractable BPA.

Ionically cross-linked hyaluronic acid: wetting, lubrication, and viscoelasticity of a modified adhesion barrier gel.

Hyaluronic acid (HA), in linear or cross-linked form, is a common component of cosmetics, personal care products, combination medical products, and medical devices. In all cases, the ability of the HA solution or gel to wet surfaces and/or disrupt and lubricate interfaces is a limiting feature of its mechanism of action. We synthesized ferric ion-cross-linked networks of HA based on an adhesion barrier, varied the degree of cross-linking, and performed wetting goniometry, viscometry, and dynamic mechanical analysis. As cross-linking increases, so do contact angle, viscosity, storage modulus, and loss modulus; thus, wetting and lubrication are compromised. These findings have implications in medical device materials, such as adhesion barriers and mucosal drug delivery vehicles.

pH effect on the synthesis, shear properties, and homogeneity of iron-crosslinked hyaluronic acid-based gel/adhesion barrier.

Iron-crosslinked hyaluronic acid hydrogel (FeHA) has been used to reduce postsurgical adhesions in patients undergoing open, gynecological surgery. The performance of FeHA gel as an adhesion barrier device is influenced by many factors, including the physicochemical gel properties, which, in turn, depend on the chemistry and conditions of the device manufacturing. In this work, we demonstrate the effect of reaction pH on rheology and homogeneity of FeHA gels formulated in house and also compare the viscoelastic properties of FeHA gels with that of uncrosslinked HA solution of similar HA concentration and ionic strength. Dynamic mechanical analyses provide evidence that the reaction of HA with Fe(III) ions leads to the formation of "weak" gels. The viscoelastic properties and homogeneity of FeHA gels vary depending on the pH at which crosslinking was initiated. When solution pH, at the start of crosslinking, varied between 1.5 and 3, the low-shear rate viscosity of FeHA varied between 10,000 and 40,000 cPoise (10-40 Pa s). The highest steady-state shear viscosity and viscoelasticity were measured when pH was around 2.6, which is similar to the pH-dependent viscoelasticity of pure HA solution. Initiating HA crosslinking at pH ≤ 3 led to relatively homogenous solutions, while crosslinking higher pH > 3 caused instantaneous gel precipitation and inhomogeneities. Sensitivity of FeHA gel properties to small variations in reaction pH clearly supports the need for a tight manufacturing control during medical device fabrication.

Breast implant adverse events during mammography: reports to the Food and Drug Administration.

OBJECTIVE: To characterize reports of adverse events occurring during mammography to women with breast implants submitted to the Food and Drug Administration (FDA). METHODS: We searched the adverse events database for any report on silicone gel breast implants or saline breast implants that included the word "mammography" or "mammogram"in the text. We also searched adverse event reports for mammographic equipment that included the term "breast implant" in the text. RESULTS: We retrieved 714 adverse event reports using this strategy. Sixty-six of these reports detailed an adverse event that occurred during mammography or described breast implant interference with mammography. The majority of these reports, 41 of 66 (62.1%), described breast implant rupture during mammography. Other adverse events reported included mammographic compression crushing implants, pain during mammography attributed to implants, inability to perform mammography because of capsular contracture or fear of implant rupture, and delayed detection of cancer attributed to implants. CONCLUSIONS: It is important that women considering breast implants be informed of these potential risks and that clinicians, radiologists, and mammographic technicians keep them in mind when imaging women with implants.