pH effect on the synthesis, shear properties, and homogeneity of iron-crosslinked hyaluronic acid-based gel/adhesion barrier†
Corresponding Author
Irada Isayeva
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903Search for more papers by this authorSrilekha Sarkar Das
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Search for more papers by this authorAndrew Chang
Gemstone Program, University of Maryland, College Park, Maryland, 20742
Search for more papers by this authorJacqueline DeFoe
Department of Chemistry, University of Chicago, Chicago, Illinois 60637
Search for more papers by this authorHoan-My Do Luu
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Search for more papers by this authorKatherine Vorvolakos
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Search for more papers by this authorDinesh Patwardhan
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Search for more papers by this authorJoyce Whang
Division of Reproductive, Abdominal and Radiological Devices (DRARD), Office of Device Evaluation (ODE)/CDRH/FDA, Silver Spring, Maryland 20903
Search for more papers by this authorSteven Pollack
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Search for more papers by this authorCorresponding Author
Irada Isayeva
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903Search for more papers by this authorSrilekha Sarkar Das
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Search for more papers by this authorAndrew Chang
Gemstone Program, University of Maryland, College Park, Maryland, 20742
Search for more papers by this authorJacqueline DeFoe
Department of Chemistry, University of Chicago, Chicago, Illinois 60637
Search for more papers by this authorHoan-My Do Luu
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Search for more papers by this authorKatherine Vorvolakos
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Search for more papers by this authorDinesh Patwardhan
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Search for more papers by this authorJoyce Whang
Division of Reproductive, Abdominal and Radiological Devices (DRARD), Office of Device Evaluation (ODE)/CDRH/FDA, Silver Spring, Maryland 20903
Search for more papers by this authorSteven Pollack
Division of Chemistry and Materials Science (DCMS)/Office of Science and Engineering Laboratories (OSEL)/Center for Devices and Radiological Health (CDRH)/Food and Dug Administration (FDA), Silver Spring, Maryland 20903
Search for more papers by this authorDisclaimer: The mention of commercial products, their source, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of the US Food and Drug Administration.
Abstract
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. © 2010 Wiley Periodicals, Inc.* J Biomed Mater Res Part B: Appl Biomater, 2010.
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