Characterization and Biocompatibility Studies of Layer-by-Layer Self-Assembled Humic Acid/Fe 3+ Films

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Characterization and Biocompatibility Studies of Layer-by-Layer Self-Assembled Humic Acid/Fe3+ Films Izabela Galeska, Tammy Hickey,1 Francis Moussy1 and Fotios Papadimitrakopoulosāˆ— Nanomaterials Optoelectronics Laboratory, Department of Chemistry, Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, CT 06269-3136 1 Center for Biomaterials & Surgical Research Center, University of Connecticut Health Center, Farmington, CT 06030-1615 ABSTRACT A semipermeable and non-inflammatory membrane is a prerequisite for the development of an implantable biosensor for continuous pain free monitoring of glucose levels in vivo. Humic acids (HAs) have been reported to have therapeutically relevant characteristics such as antiviral and anti-inflammatory.[1] This encouraged us to investigate the in vivo compatibility of HAs based multilayered films as a potential membrane material for implantable glucose sensors. Electrostatic layer-by-layer self-assembly technique of HAs with oppositely charged ferric ions was utilized to grow these films. Quartz Crystal Microbalance (QCM) and ellipsometric studies have shown repeatable, stepwise increase in mass and in film thickness during self-assembly. The growth of these assemblies exhibited strong dependence on pH and ionic strength of HAs solution and was correlated with the degree of ionization of carboxyl groups and the neutralization induced surface spreading. HAs films used in the biocompatibility study were very well tolerated by the tissue and no difference with silastic tubing, used as control, could be observed. All types of samples, including the controls, induced similar long-term tissue reaction showing almost no inflammation and a light to moderate fibrosis with some blood vessels present. INTRODUCTION Nafionā„¢, a perfluorinated ionomer, have been used as a semipermeable and protective membrane in the development of an implantable glucose sensor.[2-4] However, the in vitro and in vivo studies associated Nafion with calcification and fibrosis of the surrounding tissue, leading to decreased lifetime and sensor failure.[3, 5] Hence there is a substantiated need for an inert, glucose semi-permeable and bio-acceptable membrane, capable of resisting degradation in vivo. Humic acids (HAs) are biopolymers found in soil, sediments, water and some plants like peat and tobacco.[6-9] HAs arise from the decomposition of plant and animal tissues and with the mean residence time in soil up to 1200 years[10] are more stable than their precursors. HAs contain species of large molecular weight, ranging from a few thousand Daltons to hundreds of kiloDaltons. Their structure is dominated by aromatic building blocks, which are functionalized with -COOH, acidic and alcoholic -OH, quinonic and amine groups.[11] The therapeutically relevant characteristics of HAs[1] coupled with the ability to interact with metals[12] and absorb on a variety of surfaces such as minerals,[13-17] cellulose,[18] chitin[19] and bacteria,[15] encouraged us to investigate multilayered films of HAs