Preferred Islet Delivery Device Characteristics and Implantation Strategies of Patients With Type 1 Diabetes.

Islet delivery devices (IDDs) offer potential benefits for islet transplantation and stem cell-based replacement in type 1 diabetes. Little is known about patient preferences regarding islet delivery device characteristics and implantation strategies. Patient preferences for IDDs and implantation strategies remain understudied. We invited patients, parents and caregivers to fill in an online questionnaire regarding IDDs. An online survey gathered responses from 809 type 1 diabetes patients and 47 caregivers. We also assessed diabetes distress in a subgroup of 412 patients. A significant majority (97%) expressed willingness to receive an IDD. Preferred IDD attributes included a 3.5 cm diameter for 37.7% of respondents, while when provided with all options, 30.4% found dimensions unimportant. Respondents were open to approximately 4 implants, each with a 5 cm incision. Many favored a device functioning for 12 months (33.4%) or 24 months (24.8%). Younger participants (16-30) were more inclined to accept a 6 months functional duration (p < 0.001). Functional duration outweighed implant quantity and size (p < 0.001) in device importance. This emphasizes patients' willingness to accommodate burdens related to IDD features and implantation methods, crucial for designing future beta cell replacement strategies.

Oxidative stress in pancreatic alpha and beta cells as a selection criterion for biocompatible biomaterials.

The clinical success rate of islet transplantation, namely independence from insulin injections, is limited by factors that lead to graft failure, including inflammation, acute ischemia, acute phase response, and insufficient vascularization. The ischemia and insufficient vascularization both lead to high levels of oxidative stress, which are further aggravated by islet encapsulation, inflammation, and undesirable cell-biomaterial interactions. To identify biomaterials that would not further increase damaging oxidative stress levels and that are also suitable for manufacturing a beta cell encapsulation device, we studied five clinically approved polymers for their effect on oxidative stress and islet (alpha and beta cell) function. We found that 300 poly(ethylene oxide terephthalate) 55/poly(butylene terephthalate) 45 (PEOT/PBT300) was more resistant to breakage and more elastic than other biomaterials, which is important for its immunoprotective function. In addition, it did not induce oxidative stress or reduce viability in the MIN6 beta cell line, and even promoted protective endogenous antioxidant expression over 7 days. Importantly, PEOT/PBT300 is one of the biomaterials we studied that did not interfere with insulin secretion in human islets.

In vitro degradation profiles and in vivo biomaterial-tissue interactions of microwell array delivery devices.

To effectively apply microwell array cell delivery devices their biodegradation rate must be tailored towards their intended use and implantation location. Two microwell array devices with distinct degradation profiles, either suitable for the fabrication of retrievable systems in the case of slow degradation, or cell delivery systems capable of extensive remodeling using a fast degrading polymer, were compared in this study. Thin films of a poly(ethylene glycol)-poly(butylene terephthalate) (PEOT-PBT) and a poly(ester urethane) were evaluated for their in vitro degradation profiles over 34 weeks incubation in PBS at different pH values. The PEOT-PBT films showed minimal in vitro degradation over time, while the poly(ester urethane) films showed extensive degradation and fragmentation over time. Subsequently, microwell array cell delivery devices were fabricated from these polymers and intraperitoneally implanted in Albino Oxford rats to study their biocompatibility over a 12-week period. The PEOT-PBT implants shown to be capable to maintain the microwell structure over time. Implants provoked a foreign body response resulting in multilayer fibrosis that integrated into the surrounding tissue. The poly(ester urethane) implants showed a loss of the microwell structures over time, as well as a fibrotic response until the onset of fragmentation, at least 4 weeks post implantation. It was concluded that the PEOT-PBT implants could be used as retrievable cell delivery devices while the poly(ester urethane) implants could be used for cell delivery devices that require remodeling within a 4-12 week period.

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet-transplantation enhances immediate post-transplant islet graft function but not long-term normoglycemia.

The liver as transplantation site for pancreatic islets is associated with significant loss of islets, which can be prevented by grafting in a prevascularized, subcutaneous scaffold. Supporting vascularization of a scaffold to limit the period of ischemia is challenging and was developed here by applying liposomes for controlled release of angiogenic factors. The angiogenic capacity of platelet-derived growth factor, vascular endothelial growth factor, acidic fibroblast growth factor (aFGF), and basic FGF were compared in a tube formation assay. Furthermore, the release kinetics of different liposome compositions were tested. aFGF and L-α-phosphatidylcholine/cholesterol liposomes were selected to support vascularization. Two dosages of aFGF-liposomes (0.5 and 1.0 µg aFGF per injection) were administered weekly for a month after which islets were transplanted. We observed enhanced efficacy in the immediate post-transplant period compared to the untreated scaffolds. However, on the long-term, glucose levels of the aFGF treated animals started to increase to diabetic levels. These results suggest that injections with aFGF liposomes do improve vascularization and the immediate restoration of blood glucose levels but does not facilitate the long-term survival of islets. Our data emphasize the need for long-term studies to evaluate potential beneficial and adverse effects of vascularization protocols of scaffolds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2533-2542, 2017.

The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-ε-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets.

BACKGROUND: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally, this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here, we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) scaffold. METHOD: Three dosages of rat islets, that is, 400, 800, and 1200, were implanted in immune compromised mice to test the efficacy (n = 5). Islet transplantation under the kidney capsule served as control (n = 5). The efficacy was determined by nonfasting blood glucose measurements and glucose tolerance tests. RESULTS: Transplantation of 800 (n = 5) and 1200 islets (n = 5) into the scaffold reversed diabetes in respectively 80 and 100% of the mice within 6.8 to 18.5 days posttransplant. The marginal dose of 400 islets (n = 5) induced normoglycemia in 20%. The glucose tolerance test showed major improvement of the glucose clearance in the scaffold groups compared to diabetic controls. However, the kidney capsule was slightly more efficacious because all 800 (n = 5) and 1200 islets (n = 5) recipients and 40% of the 400 islets (n = 5) recipients became normoglycemic within 8 days. Removal of the scaffolds or kidney grafts resulted in immediate return to hyperglycemia. Normoglycemia was not achieved with 1200 islets in the unmodified skin group. CONCLUSIONS: Our findings demonstrate that the prevascularized poly (D,L-lactide-co-ε-caprolactone) scaffold maintains viability and function of islets in the subcutaneous site.

A Retrievable, Efficacious Polymeric Scaffold for Subcutaneous Transplantation of Rat Pancreatic Islets.

OBJECTIVE: We aim on developing a polymeric ectopic scaffold in a readily accessible site under the skin. SUMMARY BACKGROUND DATA: The liver as transplantation site for pancreatic islets is associated with significant loss of islets. Several extrahepatic sites were tested in experimental animals, but many have practical limitations in the clinical setting and do not have the benefit of easy accessibility. METHODS AND RESULTS: Functional survival of rat islets was tested during 7 days of culture in the presence of poly(D,L-lactide-co-ε-caprolactone) (PDLLCL), poly(ethylene oxide terephthalate)/polybutylene terephthalate (PEOT/PBT) block copolymer, and polysulfone. Tissue responses were studied in vivo after subcutaneous implantation in rats. Culture on PEOT/PBT and polysulfone profoundly disturbed function of islets, and induced severe tissue responses in vivo. Modification of their hydrophilicity did not change the suitability of the polymers. PDLLCL was the only polymer that promoted functional survival of rat islets in vitro and was associated with minor tissue reactions after 28 days. Rat islets were transplanted in the PDLLCL scaffold in a diabetic rat model. Before islet seeding, the scaffold was allowed to engraft for 28 days to allow the tissue response to dampen and to allow blood vessel growth into the device. Islet transplantation into the scaffold resulted in normoglycemia within 3 days and for the duration of the study period of 16 weeks. CONCLUSIONS: In conclusion, we found that some polymers such as PEOT/PBT and polysulfone interfere with islet function. PDLLCL is a suitable polymer to create an artificial islet transplantation site under the skin and supports islet survival.

Selection of polymers for application in scaffolds applicable for human pancreatic islet transplantation.

The liver is currently the site for transplantation of islets in humans. This is not optimal for islets, but alternative sites in humans are not available. Polymeric scaffolds in surgically accessible areas are a solution. As human donors are rare, the polymers should not interfere with functional survival of human-islets. We applied a novel platform to test the adequacy of polymers for application in scaffolds for human-islet transplantation. Viability, functionality, and immune parameters were included to test poly(D,L-lactide-co-ε-caprolactone) (PDLLCL), poly(ethylene oxide terephthalate)/polybutylene terephthalate (PEOT/PBT) block copolymer, and polysulfone. The type of polymer influenced the functional survival of human islets. In islets cultured on PDLLCL the glucagon-producing α-cells and insulin-producing ß-cells contained more hormone granules than in islets in contact with PEOT/PBT or polysulfone. This was studied with ultrastructural analysis by electron microscopy (nanotomy) during 7 d of culture. PDLLCL was also associated with statistically significant lower release of double-stranded DNA (dsDNA, a so called danger-associate molecular pattern (DAMP)) from islets on PDLLCL when compared to the other polymers. DAMPs support undesired immune responses. Hydrophilicity of the polymers did not influence dsDNA release. Islets on PDLLCL also showed less cellular outgrowth. These outgrowing cells were mainly fibroblast and some ß-cells undergoing epithelial to mesenchymal cell transition. None of the polymers influenced the glucose-stimulated insulin secretion. As PDLLCL was associated with less release of DAMPs, it is a promising candidate for creating a scaffold for human islets. Our study demonstrates that for sensitive, rare cadaveric donor tissue such as pancreatic islets it might be necessary to first select materials that do not influence functionality before proposing the biomaterial for in vivo application. Our presented platform may facilitate this selection of biomaterials.

Hybrid Polycaprolactone/Alginate Scaffolds Functionalized with VEGF to Promote de Novo Vessel Formation for the Transplantation of Islets of Langerhans.

Although regarded as a promising treatment for type 1 diabetes, clinical islet transplantation in the portal vein is still hindered by a low transplantation outcome. Alternative transplantation sites have been proposed, but the survival of extra-hepatically transplanted islets of Langerhans critically depends on quick revascularization after engraftment. This study aims at developing a new 3D scaffold platform that can actively boost vascularization and may find an application for extra-hepatic islet transplantation. The construct consists of a 3D ring-shaped polycaprolactone (PCL) scaffold with heparinized surface to electrostatically bind vascular endothelial growth factor (VEGF), surrounding a hydrogel core for islets encapsulation. Heparin immobilization improves the amount of VEGF retained by the construct, up to 3.6 fold, compared to untreated PCL scaffolds. In a chicken chorioallanthoic membrane model, VEGF immobilized on the construct enhances angiogenesis in close proximity and on the surface of the scaffolds. After 7 days, islets encapsulated in the alginate core show functional response to glucose stimuli comparable to free-floating islets. Thus, the developed platform has the potential to support rapid vascularization and islet endocrine function.

In Vitro Evaluation of Spider Silk Meshes as a Potential Biomaterial for Bladder Reconstruction.

Reconstruction of the bladder by means of both natural and synthetic materials remains a challenge due to severe adverse effects such as mechanical failure. Here we investigate the application of spider major ampullate gland-derived dragline silk from the Nephila edulis spider, a natural biomaterial with outstanding mechanical properties and a slow degradation rate, as a potential scaffold for bladder reconstruction by studying the cellular response of primary bladder cells to this biomaterial. We demonstrate that spider silk without any additional biological coating supports adhesion and growth of primary human urothelial cells (HUCs), which are multipotent bladder cells able to differentiate into the various epithelial layers of the bladder. HUCs cultured on spider silk did not show significant changes in the expression of various epithelial-to-mesenchymal transition and fibrosis associated genes, and demonstrated only slight reduction in the expression of adhesion and cellular differentiation genes. Furthermore, flow cytometric analysis showed that most of the silk-exposed HUCs maintain an undifferentiated immunophenotype. These results demonstrate that spider silk from the Nephila edulis spider supports adhesion, survival and growth of HUCs without significantly altering their cellular properties making this type of material a suitable candidate for being tested in pre-clinical models for bladder reconstruction.

Poly(amido amine)-based multilayered thin films on 2D and 3D supports for surface-mediated cell transfection.

Two linear poly(amido amine)s, pCABOL and pCHIS, prepared by polyaddition of cystamine bisacrylamide (C) with 4-aminobutanol (ABOL) or histamine (HIS), were explored to form alternating multilayer thin films with DNA to obtain functionalized materials with transfection capacity in 2D and 3D. Therefore, COS-7 cells were cultured on top of multilayer films formed by layer-by-layer dipcoating of these polymers with GFP-encoded pDNA, and the effect of the number of layers and cell seeding density on the transfection efficiency was evaluated. Multilayer films with pCABOL were found to be superior to pCHIS in facilitating transfection, which was attributed to higher incorporation of pDNA and release of the transfection agent. High amounts of transfected cells were obtained on pCABOL films, correlating proportionally over a wide range with seeding density. Optimal transfection efficiency was obtained with pCABOL films composed of 10 bilayers. Further increase in the number of bilayers only marginally increased transfection efficiency. Using the optimal multilayer and cell seeding conditions, pCABOL multilayers were fabricated on poly(ε-caprolactone) (PCL), heparinized PCL (PCL-HEP), and poly(lactic acid) (PLA) disks as examples of common biomedical supports. The multilayers were found to completely mask the properties of the original substrates, with significant improvement in cell adhesion, which is especially pronounced for PCL and PLA disks. With all these substrates, transfection efficiency was found to be in the range of 25-50% transfected cells. The pCABOL/pDNA multilayer films can also conveniently add transfection capability to 3D scaffolds. Significant improvement in cell adhesion was observed after multilayer coating of 3D-plotted fibers of PCL (with and without an additional covalent heparin layer), especially for the PCL scaffold without heparin layer and transfection was observed on both 3D PCL and PCL-HEP scaffolds. These results show that layer-by-layer dip-coating of pCABOL with functional DNA is an easy and inexpensive method to introduce transfection capability to biomaterials of any nature and shape, which can be beneficially used in various biomedical and tissue engineering applications.

Label-free Raman monitoring of extracellular matrix formation in three-dimensional polymeric scaffolds.

Monitoring extracellular matrix (ECM) components is one of the key methods used to determine tissue quality in three-dimensional scaffolds for regenerative medicine and clinical purposes. Raman spectroscopy can be used for non-invasive sensing of cellular and ECM biochemistry. We have investigated the use of conventional (confocal and semiconfocal) Raman microspectroscopy and fibre-optic Raman spectroscopy for in vitro monitoring of ECM formation in three-dimensional poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) scaffolds. Chondrocyte-seeded PEOT/PBT scaffolds were analysed for ECM formation by Raman microspectroscopy, biochemical analysis, histology and scanning electron microscopy. ECM deposition in these scaffolds was successfully detected by biochemical and histological analysis and by label-free non-destructive Raman microspectroscopy. In the spectra collected by the conventional Raman set-ups, the Raman bands at 937 and at 1062 cm(-1) which, respectively, correspond to collagen and sulfated glycosaminoglycans could be used as Raman markers for ECM formation in scaffolds. Collagen synthesis was found to be different in single chondrocyte-seeded scaffolds when compared with microaggregate-seeded samples. Normalized band-area ratios for collagen content of single cell-seeded samples gradually decreased during a 21-day culture period, whereas collagen content of the microaggregate-seeded samples significantly increased during this period. Moreover, a fibre-optic Raman set-up allowed for the collection of Raman spectra from multiple pores inside scaffolds in parallel. These fibre-optic measurements could give a representative average of the ECM Raman signal present in tissue-engineered constructs. Results in this study provide proof-of-principle that Raman microspectroscopy is a promising non-invasive tool to monitor ECM production and remodelling in three-dimensional porous cartilage tissue-engineered constructs.

Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.

Allogeneic islet transplantation into the liver has the potential to restore normoglycemia in patients with type 1 diabetes. However, the suboptimal microenvironment for islets in the liver is likely to be involved in the progressive islet dysfunction that is often observed post-transplantation. This study validates a novel microwell scaffold platform to be used for the extrahepatic transplantation of islet of Langerhans. Scaffolds were fabricated from either a thin polymer film or an electrospun mesh of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) block copolymer (composition: 4000PEOT30PBT70) and were imprinted with microwells, ∼400 µm in diameter and ∼350 µm in depth. The water contact angle and water uptake were 39±2° and 52.1±4.0 wt%, respectively. The glucose flux through electrospun scaffolds was three times higher than for thin film scaffolds, indicating enhanced nutrient diffusion. Human islets cultured in microwell scaffolds for seven days showed insulin release and insulin content comparable to those of free-floating control islets. Islet morphology and insulin and glucagon expression were maintained during culture in the microwell scaffolds. Our results indicate that the microwell scaffold platform prevents islet aggregation by confinement of individual islets in separate microwells, preserves the islet's native rounded morphology, and provides a protective environment without impairing islet functionality, making it a promising platform for use in extrahepatic islet transplantation.

Conversion of mature human ß-cells into glucagon-producing α-cells.

Conversion of one terminally differentiated cell type into another (or transdifferentiation) usually requires the forced expression of key transcription factors. We examined the plasticity of human insulin-producing ß-cells in a model of islet cell aggregate formation. Here, we show that primary human ß-cells can undergo a conversion into glucagon-producing α-cells without introduction of any genetic modification. The process occurs within days as revealed by lentivirus-mediated ß-cell lineage tracing. Converted cells are indistinguishable from native α-cells based on ultrastructural morphology and maintain their α-cell phenotype after transplantation in vivo. Transition of ß-cells into α-cells occurs after ß-cell degranulation and is characterized by the presence of ß-cell-specific transcription factors Pdx1 and Nkx6.1 in glucagon(+) cells. Finally, we show that lentivirus-mediated knockdown of Arx, a determinant of the α-cell lineage, inhibits the conversion. Our findings reveal an unknown plasticity of human adult endocrine cells that can be modulated. This endocrine cell plasticity could have implications for islet development, (patho)physiology, and regeneration.

A dual flow bioreactor with controlled mechanical stimulation for cartilage tissue engineering.

In cartilage, tissue engineering bioreactors can create a controlled environment to study chondrocyte behavior under mechanical stimulation or produce chondrogenic grafts of clinically relevant size. Here we present a novel bioreactor that combines mechanical stimulation with a two compartment system through which nutrients can be supplied solely by diffusion from opposite sides of a tissue-engineered construct. This design is based on the hypothesis that creating gradients of nutrients, growth factors, and growth factor antagonists can aid in the generation of zonal tissue-engineered cartilage. Computational modeling predicted that the design facilitates the creation of a biologically relevant glucose gradient. This was confirmed by quantitative glucose measurements in cartilage explants. In this system, it is not only possible to create gradients of nutrients, but also of anabolic or catabolic factors. Therefore, the bioreactor design allows control over nutrient supply and mechanical stimulation useful for in vitro generation of cartilage constructs that can be used for the resurfacing of articulated joints or as a model for studying osteoarthritis disease progression.

Recognizing different tissues in human fetal femur cartilage by label-free Raman microspectroscopy.

Traditionally, the composition of bone and cartilage is determined by standard histological methods. We used Raman microscopy, which provides a molecular "fingerprint" of the investigated sample, to detect differences between the zones in human fetal femur cartilage without the need for additional staining or labeling. Raman area scans were made from the (pre)articular cartilage, resting, proliferative, and hypertrophic zones of growth plate and endochondral bone within human fetal femora. Multivariate data analysis was performed on Raman spectral datasets to construct cluster images with corresponding cluster averages. Cluster analysis resulted in detection of individual chondrocyte spectra that could be separated from cartilage extracellular matrix (ECM) spectra and was verified by comparing cluster images with intensity-based Raman images for the deoxyribonucleic acid/ribonucleic acid (DNA/RNA) band. Specific dendrograms were created using Ward's clustering method, and principal component analysis (PCA) was performed with the separated and averaged Raman spectra of cells and ECM of all measured zones. Overall (dis)similarities between measured zones were effectively visualized on the dendrograms and main spectral differences were revealed by PCA allowing for label-free detection of individual cartilaginous zones and for label-free evaluation of proper cartilaginous matrix formation for future tissue engineering and clinical purposes.

3D nanofabrication of fluidic components by corner lithography.

A reproducible wafer-scale method to obtain 3D nanostructures is investigated. This method, called corner lithography, explores the conformal deposition and the subsequent timed isotropic etching of a thin film in a 3D shaped silicon template. The technique leaves a residue of the thin film in sharp concave corners which can be used as structural material or as an inversion mask in subsequent steps. The potential of corner lithography is studied by fabrication of functional 3D microfluidic components, in particular i) novel tips containing nano-apertures at or near the apex for AFM-based liquid deposition devices, and ii) a novel particle or cell trapping device using an array of nanowire frames. The use of these arrays of nanowire cages for capturing single primary bovine chondrocytes by a droplet seeding method is successfully demonstrated, and changes in phenotype are observed over time, while retaining them in a well-defined pattern and 3D microenvironment in a flat array.

Influence of the pore generator on the evolution of the mechanical properties and the porosity and interconnectivity of a calcium phosphate cement.

Porosity and interconnectivity are important properties of calcium phosphate cements (CPCs) and bone-replacement materials. Porosity of CPCs can be achieved by adding polymeric biodegradable pore-generating particles (porogens), which can add porosity to the CPC and can also be used as a drug-delivery system. Porosity affects the mechanical properties of CPCs, and hence is of relevance for clinical application of these cements. The current study focused on the effect of combinations of polymeric mesoporous porogens on the properties of a CPC, such as specific surface area, porosity and interconnectivity and the development of mechanical properties. CPC powder was mixed with different amounts of PLGA porogens of various molecular weights and porogen sizes. The major factors affecting the properties of the CPC were related to the amount of porogen loaded and the porogen size; the molecular weight did not show a significant effect per se. A minimal porogen size of 40 µm in 30 wt.% seems to produce a CPC with mechanical properties, porosity and interconnectivity suitable for clinical applications. The properties studied here, and induced by the porogen and CPC, can be used as a guide to evoke a specific host-response to maintain CPC integrity and to generate an explicit bone ingrowth.

Scanning electron microscopic assessment of coating irregularities and their precursors in unexpanded durable polymer-based drug-eluting stents.

OBJECTIVES: To assess and quantify coating irregularities on unexpanded and expanded durable polymer-based drug-eluting stents (DES) to gain insights into the origin of coating irregularities. BACKGROUND: Previous scanning electron microscopy (SEM) studies in various expanded DES revealed differences in frequency and size of coating irregularities between DES types and specific distribution patterns, however, the origin of these irregularities is unclear. METHODS: We assessed at bench side a total of 1,200 SEM images obtained in 30 DES samples (15 expanded and 15 unexpanded) of Cypher Select Plus, Taxus Liberté, Endeavor, Xience V, and resolute. RESULTS: For most coating irregularities seen on expanded DES (72%; 23/32), a matching irregularity (n = 18/23) and/or its precursor (n = 11/23) was observed in unexpanded DES. Unexpanded Cypher select showed (small) crater lesions and cracks together with precursors of "peeling." On unexpanded Taxus Liberté, thinning of polymer, small bare metal areas, wrinkles, and one precursor type were found. Unexpanded endeavor showed cracks, small bare metal areas, crater lesions, and precursors of the latter. Unexpanded Xience V and resolute mainly revealed crater lesions and their precursors. On unexpanded versus expanded DES, there was no difference in measured frequency of coating irregularities and precursors (P = ns) with the exception of more bare metal areas on expanded Taxus Liberte (P = 0.01). CONCLUSIONS: Most coating irregularities, or the potential to develop them, are inherent to the unexpanded DES. Important determinants of the formation of coating irregularities may be the stent geometry and the physical properties of the coating, while stent-balloon interaction plays no major role.

Effect of oversized partial postdilatation on coatings of contemporary durable polymer-based drug-eluting stents: a scanning electron microscopy study.

BACKGROUND: Oversized postdilation of drug-eluting stents (DES) is often performed to avoid stent malapposition. In stents implanted in long lesion or major bifurcations, extremely oversized partial postdilation may be required, which exposes DES coating to extreme forces. This study aims to assess shape and incidence of coating irregularities on durable polymer-based DES following extremely oversized partial postdilatation. METHODS: Fifteen DES samples (3 3.5 mm stents of Cypher Select plus [Cordis Europa, Roden, the Netherlands], Taxus Liberté[Boston Scientific Corp., Natick, MA, USA], Endeavor Sprint [Medtronic Vascular, Santa Rosa, CA, USA], Endeavor Resolute [Medtronic Vascular, Santa Rosa, CA, USA], and Xience V [Abbott Vascular, Santa Clara, CA, USA]) were deployed in sterile water (37 °C) at 14 atm, followed by a proximal postdilation with noncompliant 5.0-mm balloons at 18 atm. Stents were then examined with scanning electron microscopy. RESULTS: Thorough examination of a total of 660 scanning electron microscopic images demonstrated that shape and incidence of coating irregularities in the postdilated and/or transitional DES regions differed only mildly from the nonpostdilated regions. Cypher Select plus showed more peeling without bare metal aspect in the postdilated and transitional regions, and cracks were wider (P < 0.001) in the postdilated and transitional regions; in Taxus Liberté one additional irregularity (torn webbing) and more wrinkles were observed (P < 0.05 for both); in Endeavor Resolute wider cracks were found in the extremely postdilated region only (P < 0.001). Endeavor Sprint and Xience V showed no differences in shape or incidence of coating irregularities between oversized and nonoversized stent regions. CONCLUSIONS: Bench side assessment of five contemporary durable polymer-based DES with scanning electron microscopy suggests that even very aggressive stent postdilatation results in no more than mild differences in coating irregularities between postdilated and nonpostdilated stent regions.