Porous Precision-Templated 40 µm Pore Scaffolds Promote Healing through Synergy in Macrophage Receptor with Collagenous Structure and Toll-Like Receptor Signaling.

Porous precision-templated scaffolds (PTS) with uniform, interconnected, 40 µm pores have shown favorable healing outcomes and a reduced foreign body reaction (FBR). Macrophage receptor with collagenous structure (MARCO) and toll-like receptors (TLRs) have been identified as key surface receptors in the initial inflammatory phase of wound healing. However, the role of MARCO and TLRs in modulating monocyte and macrophage phenotypes within PTS remains uncharacterized. In this study, we demonstrate a synergetic relationship between MARCO and TLR signaling in cells inhabiting PTS, where induction with TLR3 or TLR4 agonists to 40 µm scaffold-resident cells upregulates the transcription of MARCO. Upon deletion of MARCO, the prohealing phenotype within 40 µm PTS polarizes to a proinflammatory and profibrotic phenotype. Analysis of downstream TLR signaling shows that MARCO is required to attenuate nuclear factor kappa B (NF-κB) inflammation in 40 µm PTS by regulating the transcription of inhibitory NFKB inhibitor alpha (NFKBIA) and interleukin-1 receptor-associated kinase 3 (IRAK-M), primarily through a MyD88-dependent signaling pathway. Investigation of implant outcome in the absence of MARCO demonstrates an increase in collagen deposition within the scaffold and the development of tissue fibrosis. Overall, these results further our understanding of the molecular mechanisms underlying MARCO and TLR signaling within PTS. Impact statement Monocyte and macrophage phenotypes in the foreign body reaction (FBR) are essential for the development of a proinflammatory, prohealing, or profibrotic response to implanted biomaterials. Identification of key surface receptors and signaling mechanisms that give rise to these phenotypes remain to be elucidated. In this study, we report a synergistic relationship between macrophage receptor with collagenous structure (MARCO) and toll-like receptor (TLR) signaling in scaffold-resident cells inhabiting porous precision-templated 40 µm pore scaffolds through a MyD88-dependent pathway that promotes healing. These findings advance our understanding of the FBR and provide further evidence that suggests MARCO, TLRs, and fibrosis may be interconnected.

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.

Novel HALO® image analysis to determine cell phenotype in porous precision-templated scaffolds.

Image analysis platforms have gained increasing popularity in the last decade for the ability to automate and conduct high-throughput, multiplex, and quantitative analyses of a broad range of pathological tissues. However, imaging tissues with unique morphology or tissues containing implanted biomaterial scaffolds remain a challenge. Using HALO®, an image analysis platform specialized in quantitative tissue analysis, we have developed a novel method to determine multiple cell phenotypes in porous precision-templated scaffolds (PTS). PTS with uniform spherical pores between 30 and 40 µm in diameter have previously exhibited a specific immunomodulation of macrophages toward a pro-healing phenotype and an overall diminished foreign body response (FBR) compared to PTS with larger or smaller pore sizes. However, signaling pathways orchestrating this pro-healing in 40 µm PTS remain unclear. Here, we use HALO® to phenotype PTS resident cells and found a decrease in pro-inflammatory CD86 and an increase in pro-healing CD206 expression in 40 µm PTS compared to 100 µm PTS. To understand the mechanisms that drive these outcomes, we investigated the role of myeloid-differentiation-primary-response gene 88 (MyD88) in regulating the pro-healing phenomenon observed only in 40 µm PTS. When subcutaneously implanted in MyD88KO mice, 40 µm PTS reduced the expression of CD206, and the scaffold resident cells displayed an average larger nuclear size compared to 40 µm PTS implanted in mice expressing MyD88. Overall, this study demonstrates a novel image analysis method for phenotyping cells within PTS and identifies MyD88 as a critical mediator in the pore-size-dependent regenerative healing and host immune response to PTS.

Monocytes contribute to a pro-healing response in 40 µm diameter uniform-pore, precision-templated scaffolds.

Porous precision-templated scaffolds (PTS) with uniformly distributed 40 µm spherical pores have shown a remarkable ability in immunomodulating resident cells for tissue regeneration. While the pore size mediated pro-healing response observed only in 40 µm pore PTS has been attributed to selective macrophage polarization, monocyte recruitment and phenotype have largely been uncharacterized in regulating implant outcome. Here, we employ a double transgenic mouse model for myeloid characterization and a multifaceted phenotyping approach to quantify monocyte dynamics within subcutaneously implanted PTS. Within 40 µm PTS, myeloid cells were found to preferentially infiltrate into the scaffold. Additionally, macrophage receptor with collagenous structure (MARCO), an innate activation marker, was significantly upregulated within 40 µm PTS. When 40 µm PTS were implanted in monocyte-depleted mice, the transcription of MARCO was significantly decreased and an increase in pro-inflammatory inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNFα) were observed. Typical of a foreign body response (FBR), 100 µm PTS significantly upregulated pro-inflammatory iNOS, secreted higher amounts of TNFα, and displayed a pore size dependent morphology compared to 40 µm PTS. Overall, these results identify a pore size dependent modulation of circulating monocytes and implicates MARCO expression as a defining subset of monocytes that appears to be responsible for regulating a pro-healing host response.

XPS and ToF-SIMS Characterization of New Biodegradable Poly(Peptide-Urethane-Urea) Block Copolymers.

New, linear, segmented poly(peptide-urethane-urea) (PPUU) block copolymers are synthesized and their surface compositions are characterized with angle dependent X-ray photoelectron spectroscopy (ADXPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). These new PPUU block copolymers contain three types of segments. The soft segment (SS) is poly(caprolactone diol) (PCL). The hard segment is lysine diisocyanate with a hydrazine chain extender. The oligopeptide segment (OPS) contains three types of amino acids (proline, hydroxyproline, and glycine). Incorporation of the OPS into the polyurethane backbone is done to provide a synthetic polymer material with controllable biodegradation properties. As biodegradation processes normally are initiated at the interface between the biomaterial and the living tissue, it is important to characterize the surface composition of biomaterials. ADXPS and ToF-SIMS results show that the surfaces of all four polymers are enriched with the PCL SS, the most hydrophobic component of the three polymer segments.

Precision-porous polyurethane elastomers engineered for application in pro-healing vascular grafts: Synthesis, fabrication and detailed biocompatibility assessment.

Unmet needs for small diameter, non-biologic vascular grafts and the less-than-ideal performance of medium diameter grafts suggest opportunities for major improvements. Biomaterials that are mechanically matched to native blood vessels, reduce the foreign body capsule (FBC) and demonstrate improved integration and healing are expected to improve graft performance. In this study, we developed biostable, crosslinked polyurethane formulations and used them to fabricate scaffolds with precision-engineered 40 µm pores. We matched the scaffold mechanical properties with those of native blood vessels by optimizing the polyurethane compositions. We hypothesized that such scaffolds promote healing and mitigate the FBC. To test our hypothesis, polyurethanes with 40 µm pores, 100 µm pores, and non-porous slabs were implanted subcutaneously in mice for 3 weeks, and then were examined histologically. Our results show that 40 µm porous scaffolds elicit the highest level of angiogenesis, cellularization, and the least severe foreign body capsule (based on a refined assessment method). This study presents the first biomaterial with tuned mechanical properties and a precision engineered porous structure optimized for healing, thus can be ideal for pro-healing vascular grafts and in situ vascular engineering. In addition, these scaffolds may have wide applications in tissue engineering, drug delivery, and implantable device.

Plasma Polymerized HMDSO Coatings For Syringes To Minimize Protein Adsorption.

Current parenteral containers used for the storage and delivery of protein-based drugs, contain silicone oil which may seep into the protein solution and can result in adsorption, aggregation and denaturation of the protein. Tightly adherent surface coatings prepared by radio frequency glow-discharge (RFGD) plasma polymerization are described in this paper. Using this robust technique, methacrylic acid (MA) (hydrophilic), hexamethyldisiloxane (HMDSO) (hydrophobic), tetraglyme (TG) (hydrophilic) were plasma polymerized onto glass. In addition, HMDSO and MA were copolymerized to create a plasma polymerized HMDSO-MA (hydrophobic) surface. Untreated glass and glass dip-coated in PDMS were used as controls. TG and MA plasma coatings adsorbed the least amount of protein in all pH conditions. Interestingly HMDSO-MA retained significantly lesser protein compared to HMDSO and dip-coated PDMS samples. In the presence of Polysorbate 80 (PS80) all plasma polymerized coatings adsorbed and retained negligible amounts of protein, compared to controls. Furthermore, the peak glide force of plasma coated syringes did not significantly increase compared to syringes without plasma coating. Due to the versatility of RFGD plasma, this process is scalable and could potentially be used for the treatment of hypodermic syringes used for the storage and delivery of protein-based therapeutics.

Polymer Surface Analysis: The Leadership and Contributions of David Briggs.

David Briggs was a surface analysis pioneer. Starting in 1970 and continuing throughout his career, Dave used his expertise, vision and ability to quickly master new surface analysis methods and solve important industrial problems. It certainly helped that he was an outstanding fund raiser in both industrial and academic settings, which ensured he always had an impressive array of the latest, most advanced surface analysis instrumentation at his disposal. He insisted on doing surface analysis correctly and through his publications, databases and books he provided the community with the needed guidelines and methods to do so. In the 1970s Dave's research was largely focused on x-ray photoelectron spectroscopy (XPS, also known as electron spectroscopy for chemical analysis (ESCA)) characterization of polymers and catalysts. He added secondary ion mass spectrometry (SIMS) to his instrumentation arsenal in the 1980s and provided many of the key, pioneering publications that described how to use this method to characterize polymer surfaces. He also did some of the first surface analysis imaging experiments in the 1980s. In the 1990s he continued his XPS and SIMS research on polymers and advanced the surface analysis community's ability to properly interpret surface analysis data through data bases and advanced data processing methods. Dave continued to publish polymer and catalysis surface analysis papers in the 2000s, but also expanded his surface analysis studies to several other topics.

Photoreactive Carboxybetaine Copolymers Impart Biocompatibility and Inhibit Plasticizer Leaching on Polyvinyl Chloride.

Protein and cell interactions on implanted, blood-contacting medical device surfaces can lead to adverse biological reactions. Medical-grade poly(vinyl chloride) (PVC) materials have been used for decades, particularly as blood-contacting tubes and containers. However, there are numerous concerns with their performance including platelet activation, complement activation, and thrombin generation and also leaching of plasticizers, particularly in clinical applications. Here, we report a surface modification method that can dramatically prevent blood protein adsorption, human platelet activation, and complement activation on commercial medical-grade PVC materials under various test conditions. The surface modification can be accomplished through simple dip-coating followed by light illumination utilizing biocompatible polymers comprising zwitterionic carboxybetaine (CB) moieties and photosensitive cross-linking moieties. This surface treatment can be manufactured routinely at small or large scales and can impart to commercial PVC materials superhydrophilicity and nonfouling capability. Furthermore, the polymer effectively prevented leaching of plasticizers out from commercial medical-grade PVC materials. This coating technique is readily applicable to many other polymers and medical devices requiring surfaces that will enhance performance in clinical settings.

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.

Highly-reactive haloester surface initiators for ARGET ATRP readily prepared by radio frequency glow discharge plasma.

New surface initiators for ARGET ATRP (activators regenerated by electron transfer atomic transfer radical polymerization) have been prepared by the plasma deposition of haloester monomers. Specifically, methyl 3-bromopropionate (M3BP), methyl 2-chloropropionate, and ethyl 2-fluoropropionate (E2FP) were plasma deposited onto glass discs using RF glow discharge plasma. This technique creates surface coatings that are resistant to delamination and rich in halogen species making them good candidates for surface initiators for ARGET ATRP. Of all the plasma polymerized surface coatings, M3BP showed the highest halogen content and was able to grow 2-hydroxyethyl methacrylate (HEMA) polymer brushes on its surface via ARGET ATRP in as little as 15 min as confirmed by XPS. Surprisingly, E2FP, a fluoroester, was also able to grow HEMA polymer brushes despite fluorine being a poor leaving group for ARGET ATRP. The versatility of RF glow discharge plasma offers a clear advantage over other techniques previously used to immobilize ARGET ATRP surface initiators.

Trifluoromethyl-functionalized poly(lactic acid): a fluoropolyester designed for blood contact applications.

Fluorinated polymers are strong candidates for development of new cardiovascular medical devices, due to their lower thrombogenicity as compared to other polymers used for cardiovascular implants. Few studies have reported the development of fluorinated polyesters and their potential in blood contact applications has never been examined. In this study, we developed a versatile method for preparing trifluoromethyl-functionalized poly(lactic acid) that can be potentially extended to prepare a new class of polyesters with various halogen or halocarbon substitutions. The resulting fluorinated polymer was hydrophobic relative to poly(lactic acid) and extracts from this polymer showed no in vitro cytotoxicity to NIH-3T3 mouse fibroblast cells. A preliminary consideration of the blood interactions of the CF3-functionalized polyester was evaluated by measuring the amount of the adsorbed albumin and fibrinogen from human blood plasma. The fluorinated polyester adsorbed and retained higher amounts of albumin and fibrinogen with a higher albumin/fibrinogen ratio as compared to poly(lactic acid), suggesting enhanced hemocompatibility. Plasma protein adsorption is the first event that occurs seconds after device implantation and controlling the adsorbed proteins will dictate the performance of medical implants.

Biomaterials: Been There, Done That, and Evolving into the Future.

Biomaterials as we know them today had their origins in the late 1940s with off-the-shelf commercial polymers and metals. The evolution of materials for medical applications from these simple origins has been rapid and impactful. This review relates some of the early history; addresses concerns after two decades of development in the twenty-first century; and discusses how advanced technologies in both materials science and biology will address concerns, advance materials used at the biointerface, and improve outcomes for patients.

BloodSurf 2017: News from the blood-biomaterial frontier.

From stents and large-diameter vascular grafts, to mechanical heart valves and blood pumps, blood-contacting devices are enjoying significant clinical success owing to the application of systemic antiplatelet and anticoagulation therapies. On the contrary, research into material and device hemocompatibility aimed at alleviating the need for systemic therapies has suffered a decline. This research area is undergoing a renaissance fueled by recent fundamental insights into coagulation and inflammation that are offering new avenues of investigation, the growing recognition of the limitations facing existing therapeutic approaches, and the severity of the cardiovascular disorders epidemic. This Opinion article discusses clinical needs for hemocompatible materials and the emerging research directions for fulfilling those needs. Based on the 2017 BloodSurf conference that brought together clinicians, scientists, and engineers from academia, industry, and regulatory bodies, its purpose is to draw the attention of the wider clinical and scientific community to stimulate further growth. STATEMENT OF SIGNIFICANCE: The article highlights recent fundamental insights into coagulation, inflammation, and blood-biomaterial interactions that are fueling a renaissance in the field of material hemocompatibility. It will be useful for clinicians, scientists, engineers, representatives of industry and regulatory bodies working on the problem of developing hemocompatible materials and devices for treating cardiovascular disorders.

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.

Collagen affinity coating for surface binding of decorin and other biomolecules: Surface characterization.

The development of biomaterials that promote tissue reconstruction and regeneration can reduce the low level, chronic inflammation and encapsulation that impact the performance of today's medical devices. Specifically, in the case of implantable sensors, the host response often leads to poor device performance that discourages permanent implantation. Our goal is to present on medical implants bioactive molecules that can promote healing rather than scarring. Localized delivery of these molecules would also minimize the possibility of adverse tissue reactions elsewhere in the body. Toward this end, the authors have developed a collagen affinity coating that binds a number of potential healing molecules and can be attached to the surface of an implanted biomaterial. This allows the creation of a wide variety of natural surface coatings that can be evaluated and tailored to promote the desired healing response. To demonstrate the efficacy of this collagen affinity coating to biospecifically bind promising healing molecules to type I collagen in vivo, the antifibrotic proteoglycan decorin was utilized. Decorin binds and renders ineffective the protein transforming growth factor beta (TGFß) that induces collagen scar production. Thus, an assembled, supramolecular structure of biomaterial-collagen-decorin-TGFß is formed. A decorin surface coating was created and characterized, illustrating the potential of this type I collagen affinity coating for widespread use with a variety of promising healing molecules. Future studies will test the implant efficacy of this type of coating.

The impact of detergents on the tissue decellularization process: A ToF-SIMS study.

Biologic scaffolds are derived from mammalian tissues, which must be decellularized to remove cellular antigens that would otherwise incite an adverse immune response. Although widely used clinically, the optimum balance between cell removal and the disruption of matrix architecture and surface ligand landscape remains a considerable challenge. Here we describe the use of time of flight secondary ion mass spectroscopy (ToF-SIMS) to provide sensitive, molecular specific, localized analysis of detergent decellularized biologic scaffolds. We detected residual detergent fragments, specifically from Triton X-100, sodium deoxycholate and sodium dodecyl sulphate (SDS) in decellularized scaffolds; increased SDS concentrations from 0.1% to 1.0% increased both the intensity of SDS fragments and adverse cell outcomes. We also identified cellular remnants, by detecting phosphate and phosphocholine ions in PAA and CHAPS decellularized scaffolds. The present study demonstrates ToF-SIMS is not only a powerful tool for characterization of biologic scaffold surface molecular functionality, but also enables sensitive assessment of decellularization efficacy. STATEMENT OF SIGNIFICANCE: We report here on the use of a highly sensitive analytical technique, time of flight secondary ion mass spectroscopy (ToF-SIMS) to characterize detergent decellularized scaffolds. ToF-SIMS detected cellular remnants and residual detergent fragments; increased intensity of the detergent fragments correlated with adverse cell matrix interactions. This study demonstrates the importance of maintaining a balance between cell removal and detergent disruption of matrix architecture and matrix surface ligand landscape. This study also demonstrates the power of ToF-SIMS for the characterization of decellularized scaffolds and capability for assessment of decellularization efficacy. Future use of biologic scaffolds in clinical tissue reconstruction will benefit from the fundamental results described in this work.

A pore way to heal and regenerate: 21st century thinking on biocompatibility.

This article raises central questions about the definition of biocompatibility, and also about how we assess biocompatibility. We start with the observation that a porous polymer where every pore is spherical, ∼40 microns in diameter and interconnected, can heal into vascularized tissues with little or no fibrosis and good restoration of vascularity (i.e., little or no foreign body reaction). The same polymer in solid form will trigger the classic foreign body reaction characterized by a dense, collagenous foreign body capsule and low vascularity. A widely used definition of biocompatibility is 'the ability of a material to perform with an appropriate host response in a specific application'. With precision-porous polymers, in direct comparison with the same polymer in solid form, we have the same material, in the same application, with two entirely different biological reactions. Can both reactions be 'biocompatible?' This conundrum will be elaborated upon and proposals will be made for future considerations and measurement of biocompatibility.

Blood compatibility assessment of polymers used in drug eluting stent coatings.

Differences in thrombosis rates have been observed clinically between different drug eluting stents. Such differences have been attributed to numerous factors, including stent design, injury created by the catheter delivery system, coating application technologies, and the degree of thrombogenicity of the polymer. The relative contributions of these factors are generally unknown. This work focuses on understanding the thrombogenicity of the polymer by examining mechanistic interactions with proteins, human platelets, and human monocytes of a number of polymers used in drug eluting stent coatings, in vitro. The importance for blood interactions of adsorbed albumin and the retention of albumin was suggested by the data. Microscopic imaging and immunostaining enhanced the interpretation of results from the lactate dehydrogenase cell counting assay and provided insight into platelet interactions, total quantification, and morphometry. In particular, highly spread platelets may be surface-passivating, possibly inhibiting ongoing thrombotic events. In many of the assays used here, poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) showed a differentiated protein deposition pattern that may contribute to the explanation of the consistently thromboresistant blood-materials interaction for fluororpolymers cited in literature. These results are supportive of one of several possible factors contributing to the good thromboresistant clinical safety performance of PVDF-HFP coated drug eluting stents.