Surface immobilized α-1 acid glycoprotein and collagen VI modulate mouse macrophage polarization and reduce the foreign body capsule.

Macrophages are widely recognized in modulating the foreign body response, and the manner in which they do so largely depends on their activation state, often referred to as their polarization. This preliminary study demonstrates that surface immobilized α-1 acid glycoprotein (AGP), as well as collagen VI (Col6) in conjunction with AGP, can direct macrophages towards the M2 polarization state in vitro and modify the foreign body response in vivo. AGP and Col6 are immobilized onto poly(2-hydroxyethyl methacrylate) (pHEMA) surfaces using carbonyl diimidazole chemistry. Mouse bone marrow derived macrophages are cultured on modified surfaces with or without lipopolysaccharide stimulation. Surface modified pHEMA discs are implanted subcutaneously into mice to observe differences in the foreign body response. After stimulation with lipopolysaccharide, macrophages cultured on AGP or Col6 modified surfaces showed a reduction in TNF-α expression compared to controls. Arg1 expression was also increased in macrophages cultured on modified surfaces. Explanted tissues showed that the foreign body capsule around implants with AGP or AGP and Col6 modification had reduced thickness, while also being more highly vascularized. These data demonstrate that α-1 acid glycoprotein and collagen VI could potentially be used for the surface modification of medical devices to influence macrophage polarization leading to a reduced and modulated foreign body response.

Surface-Treated Pellethanes: Comparative Quantification of Encrustation in Artificial Urine Solution.

Introduction: Encrustation of implanted urinary tract devices is associated with significant morbidity. Pellethane® is a polyether-based compound noted for its strength, porosity, and resistance to solvents. We assessed Pellethane thermoplastic polyurethane (TPU) with and without surface coatings 2-hydroxyethyl methacrylate (HEMA) and tetraethylene glycol dimethyl ether (TETRA) for the potential to resist encrustation in an artificial urine environment. Materials and Methods: Samples of Pellethane TPU, HEMA Pellethane TPU, TETRA Pellethane TPU, and hydrogel-coated ureteral stent (Cook®) were suspended in a batch-flow model with an artificial urine solution (AUS). Every 48 hours for 90 days, 40% of the solution was replaced with fresh AUS. All samples were stored in a 37°C incubator. Subsequently, the samples were thoroughly dried for 48 hours before weighing. Scanning electron microscopy was used to assess the degree of encrustation. Nu-Attom Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to determine the precise compositions of the encrustation specifically with regard to calcium, magnesium, and phosphate. Results: At the conclusion of the 90-day trial, the samples were analyzed, and the average mass changes were as follows: stent 63.78%, uncoated Pellethane TPU 11.50%, HEMA-coated Pellethane TPU 2.90%, and TETRA-coated Pellethane TPU 0.60%. Pellethane TPU products, and specifically those coated with HEMA and TETRA, exhibited less average mass increase and a lesser propensity to form encrustation than the traditional urinary tract stent. The mass increases noted on coated Pellethane devices were primarily ionic, whereas that of the stent was not. Conclusion: Pellethane, particularly with an HEMA-based preventative coating, may serve as a favorable alternative to traditional urinary stent material, providing its improved resistance to encrustation.

Surface fluorination of polylactide as a path to improve platelet associated hemocompatibility.

Surface-induced thrombosis is still a significant clinical concern for many types of blood-contacting medical devices. In particular, protein adsorption and platelet adhesion are important events due to their ability to trigger the coagulation cascade and initiate thrombosis. Poly(lactic acid) (PLA) has been the predominant polymer used for making bioresorbable stents. Despite long-term advantages, these stents are associated with higher rates of early thrombosis compared with permanent metallic stents. To address this issue, we modified the surface of PLA with a perfluoro compound facilitated by surface activation using radio frequency (RF) plasma. Fluoropolymers have been extensively used in blood contacting materials, such as blood vessel replacements due to their reduced thrombogenicity and reduced platelet reactivity. The compositions of plasma-treated surfaces were determined by electron spectroscopy for chemical analysis (ESCA). Also, contact angle measurements, cell cytotoxicity and the degradation profile of the treated polymers are presented. Finally, relevant blood compatibility parameters, including plasma protein adsorption, platelet adhesion and morphology, were evaluated. We hypothesized that tight binding of adsorbed albumin by fluoropolymers enhances its potential for blood-contacting applications. STATEMENT OF SIGNIFICANCE: Although bioresorbable stents made from poly(lactic acid) (PLA) may have long-term clinical advantages, they have shown higher rates of early thrombosis as compared with permanent metallic stents. To improve the thromboresistance of PLA, we developed a novel method for surface fluorination of this polymer with a perfluoro compound. Fluoropolymers (e.g., expanded polytetrafluoroethylene) have long been used in blood-contacting applications due to their satisfactory clinical performance. This is the first report of PLA surface fluorination which might be applied to the fabrication of a new generation of fluorinated PLA stents with improved platelet interaction, tunable degradability and drug release capabilities. Also, we describe a general strategy for improving the platelet interactions with biomaterials based on albumin retention.

Modulation of fibroblast inflammatory response by surface modification of a perfluorinated ionomer.

An ideal surface for implantable glucose sensors would be able to evade the events leading to chronic inflammation and fibrosis, thereby extending its utility in an in vivo environment. Nafion™, a perfluorinated ionomer, is the membrane material preferred for in situ glucose sensors. Unfortunately, the surface properties of Nafion™ promote random protein adsorption and eventual foreign body encapsulation, thus leading to loss of glucose signal over time. Details of the techniques to render Nafion™ nonprotein fouling are given in a previous article [T. I. Valdes et al., Biomaterials 29, 1356 (2008)]. Once random protein adsorption is prevented, a biologically active peptide can be covalently bonded to the treated Nafion™ to induce cellular adhesion. Cellular responses to these novel decorated Nafion™ surfaces are detailed here, including cell viability, cell spreading, and type I collagen synthesis. Normal human dermal fibroblasts (NHDFs) were cultured on control and modified Nafion™ surfaces. Findings indicate that Nafion™ modified with 10% 2-hydroxyethyl methacrylate and 90% tetraglyme created a nonfouling surface that was subsequently decorated with the YRGDS peptide. NHDFs were shown to have exhibited decreased type I collagen production in comparison to NHDF cells on unmodified Nafion™ surfaces. Here, the authors report evidence that proves that optimizing conditions to prevent protein adsorption and enhance cellular adhesion may eliminate fibrous encapsulation of an implant.

Surface modification of a perfluorinated ionomer using a glow discharge deposition method to control protein adsorption.

Nafion is the membrane material preferred for in situ glucose sensors. Unfortunately, surface properties of Nafion promote random protein adsorption and eventual foreign body encapsulation thus leading to loss of glucose signal over time. Here we detail surface modifications made by RF plasma deposition to Nafion with the intent to prevent random protein adsorption while providing enough functional sites (hydroxyl groups) to bind a biologically active peptide known to induce cellular adhesion (YRGDS). Nafion surfaces were modified by RF plasma polymerizing five different combinations of (1) tetraethylene glycol dimethyl ether (tetraglyme) and (2) 2-hydroxyethyl methacrylate (HEMA): pure tetraglyme, 2.5% HEMA with 97.5% tetraglyme, 5% HEMA with 95% tetraglyme, 10% HEMA with 90% tetraglyme, and pure HEMA. Resultant surfaces were characterized by XPS (low and high resolution), dynamic contact angle, and atomic force microscopy. Protein adsorption and retention was determined and correlated to surface layer composition. The ability to bind a cell adhesion peptide was also determined and correlated well with surface layer composition.