Antithrombogenic Surface Research Articles

Preliminary results of intracranial aneurysm treatment with derivo2heal embolization device

IntroductionThe Derivo 2 Heal Embolization Device (D2HED) is a novel flow diverter (FD) providing a fibrin-/heparin-based surface coating aiming at lower thrombogenicity. We evaluate periprocedural aspects and preliminary aneurysm occlusion efficacy for intracranial aneurysm treatment.MethodsThirty-four D2HEDs deployments (34 aneurysms, 32 patients) between 04/2021 and 10/2023 were analyzed. All patients were under dual antiplatelet therapy (dAPT). Periprocedural details, adverse events, and follow-up (FU) imaging were reviewed by consultant-level neuroradiologists. Complication rates and aneurysm occlusion efficacy are compared with performance data of other FDs based on literature research.ResultsEach intervention succeeded in the deployment of one D2HED. Significant and/or increased intraaneurysmal contrast stagnation immediately after D2HED deployment was seen in 73.5% of cases according to O’Kelly-Marotta (OKM) grading scale. Clinically relevant early adverse events occurred in three patients: Among them two cases with fusiform aneurysms in the posterior circulation (ischemic events, early in-stent-thrombosis) and one patient (ischemic event) out of the majority of 31 treated internal carotid artery aneurysms (3,2%). Regarding mid-term FU (> 165 days), one aneurysm did not show progressive occlusion presumably caused by a prominent A1 segment arising from the terminal ICA aneurysm itself. Apart from that, mid-term complete / partial occlusion rates of 80% / 20% could be demonstrated.ConclusionOur case series - although suffering from restricted sample size - suggests a potential effectiveness of D2HED in managing intracranial aneurysms. Further studies with larger samples are warranted to quantify long-term occlusion efficacy and the impact of antithrombogenic surface coating on the necessary (d)APT.

Polymer-Drug Anti-Thrombogenic and Hemocompatible Coatings as Surface Modifications.

Since the 1960s, efforts have been made to develop new technologies to eliminate the risk of thrombosis in medical devices that come into contact with blood. Preventing thrombosis resulting from the contact of a medical device, such as an implant, with blood is a challenge due to the high mortality rate of patients and the high cost of medical care. To this end, various types of biomaterials coated with polymer-drug layers are being designed to reduce their thrombogenicity and improve their hemocompatibility. This review presents the latest developments in the use of polymer-drug systems to produce anti-thrombogenic surfaces in medical devices in contact with blood, such as stents, catheters, blood pumps, heart valves, artificial lungs, blood vessels, blood oxygenators, and various types of tubing (such as for hemodialysis) as well as microfluidic devices. This paper presents research directions and potential clinical applications, emphasizing the importance of continued progress and innovation in the field.

Influence of electrical polarization on thrombogenicity of titania nanotubes

AbstractThe development of hemocompatible biomaterials with antithrombogenic surface coatings remains a challenge in cardiovascular applications. There is interest in negatively charged surfaces that inhibit thrombus formation through electrostatic repulsion between the biomaterial surface and negatively charged platelets. Hence, the present study investigated the influence of electrical polarization on the thrombogenicity of titania nanotubes (TNT), which are promising candidates for inhibiting thrombogenicity via surface modification. TNTs were formed on commercially pure titanium plate by the electrochemical anodization technique using platinum as a counter electrode at 60 V for 24 h with two kinds of electrolytes (hydrofluoric acid diluted with dimethyl sulfoxide [D‐TNT] or ethylene glycol [E‐TNT]) followed by an annealing at 540°C for 3 h in air. Both TNTs were mixture of anatase and rutile, and the D‐TNT had a diameter of 108.76 ± 2.55 nm and the E‐TNT, 53.833 ± 2.42 nm. The TNTs were electrically polarized at 100 V of DC field and 400°C for 1 h. Water contact angle measurements showed that the non‐polarized (0‐) TNT surface was hydrophilic whereas the positively (P‐) or negatively (N‐) polarized TNT surfaces showed high‐hydrophilicity. Antithrombogenicity was evaluated using the thrombus coverage area ratio (TCAR) after soaking the TNTs in bovine whole blood. The TCARs for 0‐polarized E‐ and D‐TNTs were 5.30 ± 4.34% and 36.3 ± 5.8% and for P‐polarized E‐TNT and D‐TNT were 1.50 ± 0.77% and 2.76 ± 1.07%, whereas no thrombus formation (0 ± 0%) for N‐polarized E‐TNT and very few thrombus formation (0.12 ± 0.22%) for N‐polarized D‐TNT. The electrostatic repulsion between the N‐polarized E‐TNTs and platelets completely inhibits thrombus formation, which cannot be achieved by the nanomorphology and high‐hydrophilicity of other TNTs. Hence, N‐TNTs formed by electrical polarization are potential candidates for cardiovascular devices, such as artificial heart valves with long‐term hemocompatibility.

Multicenter study of the safety and effectiveness of intracranial aneurysm treatment with the p64MW-HPC flow modulation device

Background and purpose The new p64 flow diverter with hydrophilic polymer coating (HPC) was designed to reduce thrombogenicity. To date, it is unclear how antithrombogenic surface modifications affect neoendothelialization and thrombus formation in patients with unruptured intracranial aneurysms. The purpose of this study was to evaluate the safety and effectiveness of the p64MW-HPC in the treatment of unruptured aneurysms of small to giant size and of both the anterior and posterior circulation. Materials and methods Between March 2020 and October 2022 all patients with unruptured intracranial aneurysms treated with the p64MW-HPC were included at five neurovascular centers. Demographic data, aneurysm characteristics, antiplatelet therapy, procedural complications, and clinical and angiographic outcomes were recorded. Results A total of 100 patients with 100 unruptured intracranial aneurysms met the inclusion criteria. Eighty-three aneurysms were classified as saccular, 12 aneurysms were fusiform, 4 aneurysms dissecting, and 1 aneurysm was blister-like. Dual antiplatelet therapy with Clopidogrel and Aspirin was given in 68 cases, and with Ticagrelor and Aspirin in 24 cases. Technical issues with deployment were encountered in 14 cases (torsion ( n = 3), foreshortening ( n = 8), and incomplete opening ( n = 3)). Ischemic stroke occurred in a total of seven cases. In one patient a wire perforation and subsequent severe ICH occurred. Complete aneurysm occlusion at angiographic follow-up (mean time = 7 months) was seen in 73% and adequate occlusion in 93%. Conclusion This study is the largest multicenter study to date documenting the safety and effectiveness of the new antithrombogenic p64MW-HPC in the treatment of unruptured intracranial aneurysms of the anterior and posterior circulation.

Intracranial aneurysms treatment using new generation FRED X flow diverters with antithrombotic coating and preoperative PreSize Neurovascular software simulation: literature review and own clinical observations analysis

Objective: Evaluate the possibilities of treating giant intracranial aneurysms and complex anatomy aneurysms by implanting new generation of FRED X flow diverters (MicroVention, USA) with antithrombogenic surface subject to preoperative virtual modeling and sizing with PreSize Neurovascular software (Oxford Heartbeat Ltd, Great Britain). Materials and Methods. FRED X flow diverters with antithrombogenic surface were implanted in 7 patients with giant cerebral aneurysms and complex anatomy aneurysms in the Endovascular Center at Mechnikov Dnipropetrovsk Regional Clinical Hospital, Dnipro, within two months (May 2, 2023 to June 27, 2023). Our study group consisted of 4 (57.1%) female patients and 3 (42.9%) male patients (p=1.0). The average age was 50.4±13.7. 4 patients had single intracranial aneurysms and 3 patients had multiple aneurysms. 2 patients had 2 aneurysms and 1 patient had 4 aneurysms. 3 patients had a hemorrhagic clinical course of the disease (spontaneous subarachnoid hemorrhage in the history), 3 patients had asymptomatic aneurysms, and 1 patient had a pseudotumorous aneurysm. Results. All 7 patients underwent the ICA aneurysm(s) surgery. 3 patients had a flow diverter implanted at the level of multiple aneurysms (in 2 patients, 2 aneurysms; in 1 patient, 3 aneurysms). 2 patients, in addition to flow diverter implantation, underwent coil aneurysms embolization (using jailing technique). In all patients, the flow diverter was implanted under dual (ticagrelor and acetylsalicylic acid) antiplatelet therapy. 3 patients with a history of subarachnoid aneurysmal hemorrhage received a loading dose of dual antiplatelet therapy immediately before the flow diverter implantation. In one patient with a complex closed siphon shape, balloon angioplasty was required to optimize flow diverter opening to the arterial wall. In all other 6 patients, the flow diverters were opened in a controlled manner with a Push & Pull technique variant: Load/Tension Unsheath technique. Conclusions: In the endovascular treatment of giant and complex aneurysms, the use of new generation FRED X flow diverters (MicroVention, USA) with antithrombogenic coating subject to proper diverters sizing with PreSize Neurovascular software does not cause technical difficulties and is controlled.

Fucoidan and topography modification improved in situ endothelialization on acellular synthetic vascular grafts.

Thrombogenesis remains the primary failure of synthetic vascular grafts. Endothelial coverage is crucial to provide an antithrombogenic surface. However, most synthetic materials do not support cell adhesion, and transanastomotic endothelial migration is limited. Here, a surface modification strategy using fucoidan and topography was developed to enable fast in situ endothelialization of polyvinyl alcohol, which is not endothelial cell-adhesive. Among three different immobilization approaches compared, conjugation of aminated-fucoidan promoted endothelial monolayer formation while minimizing thrombogenicity in both in vitro platelet rich plasma testing and ex vivo non-human primate shunt assay. Screening of six topographical patterns showed that 2μm gratings increased endothelial cell migration without inducing inflammation responses of endothelial cells. Mechanistic studies demonstrated that fucoidan could attract fibronectin, enabling integrin binding and focal adhesion formation and activating focal adhesion kinase (FAK) signaling, and 2μm gratings further enhanced FAK-mediated cell migration. In a clinically relevant rabbit carotid artery end-to-side anastomosis model, 60% in situ endothelialization was observed throughout the entire lumen of 1.7mm inner diameter modified grafts, compared to 0% of unmodified graft, and the four-week graft patency also increased. This work presents a promising strategy to stimulate in situ endothelialization on synthetic materials for improving long-term performance.

Poly(2-Methoxyethyl Acrylate) (PMEA)-Coated Anti-Platelet Adhesive Surfaces to Mimic Native Blood Vessels through HUVECs Attachment, Migration, and Monolayer Formation

Confluent monolayers of human umbilical vein endothelial cells (HUVECs) on a poly(2-methoxyethyl acrylate) (PMEA) antithrombogenic surface play a major role in mimicking the inner surface of native blood vessels. In this study, we extensively investigated the behavior of cell–polymer and cell–cell interactions by measuring adhesion strength using single-cell force spectroscopy. In addition, the attachment and migration of HUVECs on PMEA-analogous substrates were detected, and the migration rate was estimated. Moreover, the bilateral migration of HUVECs between two adjacent surfaces was observed. Furthermore, the outer surface of HUVEC was examined using frequency-modulation atomic force microscopy (FM-AFM). Hydration was found to be an indication of a healthy glycocalyx layer. The results were compared with the hydration states of individual PMEA-analogous polymers to understand the adhesion mechanism between the cells and substrates in the interface region. HUVECs could attach and spread on the PMEA surface with stronger adhesion strength than self-adhesion strength, and migration occurred over the surface of analogue polymers. We confirmed that platelets could not adhere to HUVEC monolayers cultured on the PMEA surface. FM-AFM images revealed a hydration layer on the HUVEC surfaces, indicating the presence of components of the glycocalyx layer in the presence of intermediate water. Our findings show that PMEA can mimic original blood vessels through an antithrombogenic HUVEC monolayer and is thus suitable for the construction of artificial small-diameter blood vessels.

Investigation of heparin-loaded poly(ethylene glycol)-based hydrogels as anti-thrombogenic surface coatings for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO), a critical life-sustaining tool, faces significant challenges for the maintenance of normal haemostasis due to the large volume of circulating blood continuously in contact with artificial surfaces, hyperoxia and excessive shear stresses of the extracorporeal circuit. From a biomaterials perspective, it has been hypothesised that drug eluting coatings composed of haemocompatible hydrogels loaded with an anticoagulant drug could potentially enhance the haemocompatibility of the circuit. Poly(ethylene glycol) (PEG) has been well established as a biocompatible and anti-fouling material with wide biomedical application. Unfractionated heparin is the most commonly used anticoagulant for ECMO. In the present study, the feasibility of using heparin-loaded PEG-based hydrogels as anti-thrombogenic surface coatings for ECMO was investigated. The hydrogels were synthesised by photopolymerisation using poly(ethylene glycol) diacrylate (PEGDA) as the crosslinking monomer and poly(ethylene glycol) methacrylate (PEGMA) as the hydrophilic monomer, with heparin loaded into the pre-gel solution. Factors which could affect the release of heparin were investigated, including the ratio of PEGDA/PEGMA, water content, loading level of heparin and the flow of fluid past the hydrogel. Our results showed that increased crosslinker content and decreased water content led to slower heparin release. The hydrogels with water contents of 60 wt% and 70 wt% could achieve a sustained heparin release by adjusting the ratio of PEGDA/PEGMA. The anticoagulation efficacy of the released heparin was evaluated by measuring the activated clotting time of whole blood. The hydrogels with desirable heparin release profiles were prepared onto poly(4-methyl-1-pentene) (PMP) films with the same chemical composition as the PMP ECMO membranes. The coatings showed sustained heparin release with a cumulative release of 70-80% after 7 days. Haemocompatibility tests demonstrated that PEG hydrogel coatings significantly reduced platelet adhesion and prolonged plasma recalcification time. These results suggest that heparin-loaded PEG hydrogels are potential anti-thrombogenic coatings for ECMO.

Anti-thrombogenic Surface Coatings for Extracorporeal Membrane Oxygenation: A Narrative Review.

Extracorporeal membrane oxygenation (ECMO) is used in critical care to manage patients with severe respiratory and cardiac failure. ECMO brings blood from a critically ill patient into contact with a non-endothelialized circuit which can cause clotting and bleeding simultaneously in this population. Continuous systemic anticoagulation is needed during ECMO. The membrane oxygenator, which is a critical component of the extracorporeal circuit, is prone to significant thrombus formation due to its large surface area and areas of low, turbulent, and stagnant flow. Various surface coatings, including but not limited to heparin, albumin, poly(ethylene glycol), phosphorylcholine, and poly(2-methoxyethyl acrylate), have been developed to reduce thrombus formation during ECMO. The present work provides an up-to-date overview of anti-thrombogenic surface coatings for ECMO, including both commercial coatings and those under development. The focus is placed on the coatings being developed for oxygenators. Overall, zwitterionic polymer coatings, nitric oxide (NO)-releasing coatings, and lubricant-infused coatings have attracted more attention than other coatings and showed some improvement in in vitro and in vivo anti-thrombogenic effects. However, most studies lacked standard hemocompatibility assessment and comparison studies with current clinically used coatings, either heparin coatings or nonheparin coatings. Moreover, this review identifies that further investigation on the thrombo-resistance, stability and durability of coatings under rated flow conditions and the effects of coatings on the function of oxygenators (pressure drop and gas transfer) are needed. Therefore, extensive further development is required before these new coatings can be used in the clinic.

A rechargeable anti-thrombotic coating for blood-contacting devices

Despite the potential of anti-thrombogenic coatings, including heparinized surfaces, to improve the performance of blood-contacting devices, the inevitable deterioration of bioactivity remains an important factor in device failure and related thrombotic complications. As a consequence, the ability to restore the bioactivity of a surface coating after implantation of a blood-contacting device provides a potentially important strategy to enhance its clinical performance. Here, we report the regeneration of a multicomponent anti-thrombogenic coating through use of an evolved sortase A to mediate reversible transpeptidation. Both recombinant thrombomodulin and a chemoenzymatically synthesized ultra-low molecular weight heparin were repeatedly and selectively immobilized or removed in a sequential, alternating, or simultaneous manner. The generation of activated protein C (aPC) and inhibition of activated factor X (FXa) was consistent with the molecular composition of the surface. The fabrication of a rechargeable anti-thrombogenic surface was demonstrated on an expanded polytetrafluoroethylene (ePTFE) vascular graft with reconstitution of the surface bound coating 4 weeks after in vivo implantation in a rat model.

Anti-thrombotic polymer surfaces modified with zwitterionic and fluorinated surface-migrating oligomers

For the development of anti-thrombotic biomaterials, blending a surface migrating oligomer (SMO) in a biomedical polymer has been focused as a promising alternative way to conventional coatings. In this study, novel SMOs with the polyurethane backbone containing zwitterion and fluorine were synthesized and blended it with polyvinyl chloride (PVC) to confer synergistic anti-thrombotic performance through anti-fouling effect. Studies using elemental analysis, FT IR, 1H NMR and ion chromatography demonstrated the successful incorporation of sulfobetaine and fluorine in the SMOs. The thermal analysis characterized PVC/SMO-blended films with varied glass transition temperatures. X-ray photoelectron spectroscopy represented high compositions of sulfur and fluorine atoms at the surface of SMOs-blended PVCs, proving that SMOs effectively migrated toward the surface during the film preparation. The SMOs-blended PVC films not only improved resistivity to the adsorption of albumin and fibrinogen but also inhibited the adhesion and activation of human platelets, meaning enhanced anti-fouling effect and thereby anti-thrombogenicity. In particular, the SMOs-blended PVCs with both sulfobetaine and fluorine were synergistically effective in the reduction in cell/platelet adhesion and protein adsorption. In summary, our results give a positive cue that the novel type of SMOs containing both sulfobetaine and fluorinated segments can be a promising material for anti-thrombogenic surface modification in cardiovascular applications.

Antithrombogenic poly(2-methoxyethyl acrylate) elastomer via triblock copolymerization with poly(methyl methacrylate)

For the development of blood-contacting biomedical devices, preventing platelet adhesion and avoiding subsequent thrombosis through antithrombogenic surface are vitally important. Poly (2-methoxyethyl acrylate) (PMEA) is a synthetic viscous polymer with an excellent antithrombogenic property, which has already been used as an antithrombogenic coating for biomedical purposes. The PMEA coating, however, can be easily broken due to its liquid-like feature, since the glass transition temperature (Tg) of PMEA is at −25οC. Solidifying PMEA has, therefore, been desperately desired for the improvement of the stability of PMEA coating. Also, once solidified, PMEA could be utilized not only for coating but also for structural materials for medical devices, expanding the application range of PMEA. In this study, PMEA was first solidified by triblock copolymerization with poly (methyl methacrylate) (PMMA) to obtain thermoplastic elastomers with excellent antithrombogenicity. We synthesized PMMA-PMEA-PMMA triblock copolymers with different volume fractions of PMMA (fMMA) by atom transfer radical polymerization (ATRP). The synthesis and the chemical structures of the new triblock copolymers were characterized and confirmed by proton nuclear magnetic resonance (1H NMR) analyses and gel permeation chromatography (GPC). The synthesized elastomeric triblocks were then compression-molded at 180οC to obtain solid transparent films. The tensile property was measured and the drastic change from the soft-elastomer phase to the hard-plastic phase was clearly observed by varying fMMA. It was found that the new triblocks possessed significantly higher tensile strengths than the other solidified PMEA by the previous studies. The platelet adhesion test revealed that the number of adherent platelets on the triblocks with fMMA of 0.12 and 0.40 was almost the same as that on pure PMEA, indicating that the synthesized triblocks possessed excellent antithrombogenicity similar to liquid PMEA. Further investigation on hydrated water and microphase-separated structures eventually revealed that the new triblock copolymers with a sufficient amount of intermediate water or with microphase separation on the surface resulted in excellent antithrombogenicity.

Evaluation of Antithrombogenic pHPC on CoCr Substrates for Biomedical Applications

Bare metal endovascular implants pose a significant risk of causing thrombogenic complications. Antithrombogenic surface modifications, such as phenox’s “Hydrophilic Polymer Coating” (pHPC), which was originally developed for NiTi implants, decrease the thrombogenicity of metal surfaces. In this study, the transferability of pHPC onto biomedical CoCr-based alloys is examined. Coated surfaces were characterized via contact-angle measurement and atomic force microscopy. The equivalence of the antithrombogenic effect in contact with whole human blood was demonstrated in vitro for CoCr plates compared to NiTi plates on a platform shaker and for braided devices in a Chandler loop. Platelet adhesion was assessed via scanning electron microscopy and fluorescence microscopy. The coating efficiency of pHPC on CoCr plates was confirmed by a reduction of the contact angle from 84.4° ± 5.1° to 36.2° ± 5.2°. The surface roughness was not affected by the application of pHPC. Platelet adhesion was significantly reduced on pHPC-coated specimens. The platelet covered area was reduced by 85% for coated CoCr plates compared to uncoated samples. Uncoated braided devices were completely covered by platelets, while on the pHPC-coated samples, very few platelets were visible. In conclusion, the antithrombogenic effect of pHPC coating can be successfully applied on CoCr plates as well as stent-like CoCr braids.

Outcome of Flow Diverters with Surface Modifications in Treatment of Cerebral Aneurysms: Systematic Review and Meta-analysis.

Newer flow diverters are enhanced with antithrombogenic surface modifications like the Pipeline Embolization Device with Shield Technology and the Derivo Embolization Device and are purported to facilitate deployment and reduce ischemic events. Our aim was to review the safety and efficacy of surface-modified flow diverters in treating patients with cerebral aneurysms. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review and meta-analysis covering 3 major data bases and gray literature between 2014 and 2019. Two reviewers independently reviewed human studies of surface-modified flow diverters for eligibility based on predetermined criteria. The random effects model and Freeman-Tukey arcsine transformation were used to pool efficacy outcomes (technical success, aneurysm occlusion at 6 and 12 months) and safety outcomes (mortality, morbidity, all ischemia, and serious ischemia). Subgroup analysis was performed to compare outcomes between 2 different flow diverters. Eight single-arm case series involving 911 patients and 1060 aneurysms were included. The median follow-up was 8.24 months. Pooled estimate for technical success was 99.6%, while the aneurysm occlusion at 6 and 12 months were 80.5%, and 85.6%, respectively. Pooled estimates for mortality, morbidity, total ischemia, and serious ischemia rates were 0.7%, 6.0%, 6.7%, and 1.8%, respectively. Most studies were of good quality, and no significant heterogeneity was observed. Limitations include a retrospective, observational design in some studies; heterogeneous and underreported antiplatelet therapy; and potential performance and ecologic bias. Early-to-midterm safety and efficacy for surface-modified flow diverters appear comparable with older devices, especially for small, unruptured anterior circulation aneurysms. Long-term clinical data are required to further corroborate these results.

Toward Innovative Hemocompatible Surfaces: Crystallographic Plane Impact on Platelet Activation.

The anticoagulation treatment of cardiovascular patients, which is mandatory after implantation of heart valves or stents, has significantly adverse effects on life quality. This treatment can be reduced or even circumvented by developing novel antithrombogenic surfaces of blood-contacting implants. Thus, we aim to discover materials exhibiting outstanding hemocompatibility compared to other available synthetic materials. We present promising surficial characteristics of single crystalline alumina in terms of platelet activation inhibition. In order to elucidate the relation between its crystallographic properties including the plane orientation and blood cell behavior, we examined endothelialization, cytocompatibility, and platelet activation at the blood-alumina interfaces in a controlled experimental setup. We observed that the cell response is highly sensitive to the plane orientation and differs significantly for (0001) and (11-20) planes of Al2O3. Our results reveal for the first time the dependence of platelet activation on crystallographic orientation, which is assumed to be a critical condition controlling the thrombogenicity. Additionally, we used an endothelial cell monolayer as an internal control since endothelial cells have an impact on vessel integrity and implant acceptance. We successfully demonstrate that Al2O3(11-20) exhibits enhanced hemocompatibility in contrast to Al2O3(0001) and is comparable to the physiological endothelial monolayer in vitro.

Glycocalyx‐Like Hydrogel Coatings for Small Diameter Vascular Grafts

AbstractNovel biological vascular conduits, such as decellularized tissue engineered vascular grafts (TEVGs) are hindered by high thrombogenicity. To mimic the antithrombogenic surface of native vessels with a continuous glycosaminoglycan layer that is present on endothelial cells (ECs), a hyaluronic acid (HA) modified surface is established, to effectively shield blood platelets from collagen‐triggered activation. Using the amine groups present on 4 mm diameter decellularized TEVGs, a continuous HA hydrogel coating is built via a bifunctional thiol‐reactive cross‐linker, thereby avoiding nonspecific collagen matrix cross‐linking. The HA hydrogel layer recreates a luminal wall, “hiding” exposed collagen from the bloodstream. In vitro blood tests show that adhered platelets, fibrinogen absorption, and fibrin formation on HA‐coated decellularized TEVGs are significantly lower than on uncoated decellularized TEVGs. The HA surface also inhibits macrophage adhesion in vitro. HA‐coated decellularized syngeneic rat aortae (≈1.5 mm diameter), and TEVGs in rat and canine models, respectively, are protected from aggressive thrombus formation, and preserve normal blood flow. Re‐endothelialization is also observed. HA‐coated TEVGs may be an off‐the‐shelf small‐diameter vascular graft with dual benefits: antithrombogenic protection and promotion of endothelium.

Anti-thrombogenic coatings for devices in neurointerventional surgery: Case report and review of the literature

Background:Stent-assisted coiling and extra-saccular flow diversion require dual anti-platelet therapy due to the thrombogenic properties of the implants. While both methods are widely accepted, thromboembolic complications and the detrimental effects of dual anti-platelet therapy remain a concern. Anti-thrombogenic surface coatings aim to solve both of these issues. Current developments are discussed within the framework of an actual clinical case.Case description:A 33-year-old male patient lost consciousness while doing sport and was administered 500 mg acetylsalicylic acid on site. Computed tomography revealed a massive subarachnoid haemorrhage, and digital subtraction angiography showed an aneurysm of the right middle cerebral artery. Stent-assisted coiling using a neck bridging device with a hydrophilic coating (pCONUS_HPC) was considered as an appropriate approach. Another 500 mg acetylsalicylic acid IV was given. After the single anti-platelet therapy was seen to be effective, a pCONUS_HPC was implanted, and the aneurysm sac subsequently fully occluded using coils. No thrombus formation was encountered. During the following days, 2 × 500 mg acetylsalicylic acid IV daily were required to maintain single anti-platelet therapy, monitored by frequent response testing. Follow-up digital subtraction angiography after 13 days confirmed the occlusion of the aneurysm and the patency of the middle cerebral artery.Conclusion: A variety of ways to reduce the thrombogenicity of neurovascular stents is discussed. Hydrophilic surface coatings are a valid concept to improve the haemocompatibility of neurovascular implants while avoiding the use of dual anti-platelet therapy. Phosphorylcholine and phenox hydrophilic polymer coating are currently the most promising candidates. This concept is supported by anecdotal experience. However, formalised registries and randomised trials are currently being established.

SPR biosensor for quantification of fetuin-A as a promising multibiomarker.

Early diagnosis of ongoing malignant disease is crucial to improve survival rate and life quality of the patients and requires sensitive detection of specific biomarkers e.g. prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), etc. In spite of current technological advances, malignant diseases are still identified in rather late stages, which have detrimental effect on the prognosis and treatment of the disease. Here, we present a biosensor able to detect fetuin-A, a potential multibiomarker. The biosensing platform is based on polymer brush combining antifouling monomer units of N-(2-hydroxypropyl)methacrylamide (HPMA) and carboxybetaine methacrylamide (CBMAA), statistically copolymerized by surfaceinitiated atom transfer radical polymerization. The copolymer poly(HPMA-co-CBMAA) exhibits excellent non-fouling properties in the most relevant biological media (i.e. blood plasma) as well as antithrombogenic surface properties by preventing the adhesion of blood components (i.e. leukocytes; platelets; and erythrocytes). Moreover, the polymer brush can be easily functionalized with biorecognition elements maintaining high resistance to blood fouling and the binding capacity can be regulated by tuning the ratio between CBMAA and HPMA units. The superior antifouling properties of the copolymer even after biofunctionalization were exploited to fabricate a new plasmonic biosensor for the analysis of fetuin-A in real clinical blood plasma samples. The assay used in this work can be explored as labelfree affinity biosensor for diagnostics of different biomarkers in real clinical plasma samples and to shift the early biomarker detection toward novel biosensor technologies allowing point of care analysis.

Surface topography of polylactic acid nanofibrous mats: influence on blood compatibility.

Fabricating nanofibrous scaffolds with robust blood compatibility remains an unmet challenge for cardiovascular applications since anti-thrombogenic surface coatings did not withstand physiological shear force. Hence, the present study envisages the influence of smooth and porous topographies of poly(lactic acid) (PLA) nanofibers on hemocompatibility as it could offer time-independent blood compatibility. Further, recent studies have evolved to integrate various contrasting agents for augmenting the prognostic properties of tissue engineered scaffolds; an attempt was also made to synthesize Curcumin-superparamagnetic iron oxide nanoparticle complex (Cur-SPION) as a contrasting agent and impregnated into PLA nanofibers for evaluating the blood compatibility. Herein, electrospun nanofibers of PLA with different topographies (smooth and porous) were fabricated and characterized for surface morphology, zeta potential, fluorescence, and crystallinity. The scaffolds with smooth, porous and rough surface topographies were thoroughly investigated for its hemocompatibility by evaluating hemolysis percentage, platelet adhesion, in vitro kinetic clotting time, serum protein adsorption, plasma recalcification time (PRT), capture and release of erythrocytes. Although the nanofibers of all three groups showed acceptable hemolytic percentage (HP < 5%), the adhered RBCs on Cur-SPION based fibers undergo morphological transformation from biconcave discocytes to echinocytes with cube-like protrusions. On the contrary, no morphological changes were observed in RBCs cultured on smooth and porous nanofibers. Porous fibers exhibited excellent anti-thrombogenic property and adhered lesser platelets and maintained the discoidal morphology of native platelets. Cur-SPION integrated PLA nanofibers showed inactivated platelets with anti-thrombogenic activity compared to smooth nanofibers. In conclusion, PLA nanofibers porous topography did not affect the RBC membrane integrity and maintained discoidal morphology of platelets with superior anti-thrombogenic activity. However, smooth and Cur-SPION integrated PLA nanofibers were found to activate the platelets and deform the RBC membrane integrity, respectively. Hence, the nanofibers with porous structures provide an ideal topography for time-independent hemocompatibility.

Shear Conditioning of Adipose Stem Cells for Reduced Platelet Binding to Engineered Vascular Grafts.

Conferring antithrombogenicity to tissue-engineered vascular grafts remains a major challenge, especially for urgent bypass grafting that excludes approaches based on expanding autologous endothelial cells (ECs) that requires weeks of cell culture. Adipose-derived stem cells (ASCs) are available from most patients in sufficient number for coronary bypass graft seeding and may be effective as allogeneic cells. We thus compared the adhesion and platelet binding of human ASCs that were shear conditioned with constant and pulsatile shear stress (SS) after seeding the cells on a biologically engineered matrix suitable for arterial grafts. A monolayer of cells was maintained up to 15 dyn/cm2 constant SS and up to 15 dyn/cm2 mean pulsatile SS for 6 days of shear flow. Platelet binding was reduced from 83% to 6% of surface area and nitric oxide production was increased 23-fold with 7.5-15 dyn/cm2 constant SS, but not pulsatile SS, relative to cells cultured statically on the matrix for 6 days. The reduction in platelet binding varied from no reduction to maximum reduction over a constant shear range of ∼2 to 4 dyn/cm2, respectively. Collectively, the study supports the potential use of ASCs to seed the luminal surface of a vascular graft made from this biologically engineered matrix to confer an antithrombogenic surface during the development of an endothelium from the seeded cells or the surrounding blood and tissue.