Tyramine-enhanced zwitterion hyaluronan hydrogel coating for anti-fouling and anti-thrombosis

Zwitterions have aroused much interest to endow implantable medical devices with anti-fouling and anti-thrombosis performance,due to their ability to form a hydrated layer that can provide a good barrier against protein and cell adhesion. Herein,tyramine modified sulfobetaine-derived sodium hyaluronan(HST) hydrogel coating was fabricated, in which hyaluronan(HA)was used as polysaccharide skeleton to graft zwitterionic sulfobetaine, and tyramine was introduced as crosslinker to construct both the network of hydrogel and a strong covalent bond between coating and substrate. Hydrogel coating was prepared by spin coating or painting HST prepolymer solution under ultraviolet light irradiation. The obtained HST hydrogel coating shows good stability. Moreover, in addition to its outstanding anti-fouling performance and good biocompatibility, it can effectively prevent thrombosis in blood circulation ex vivo. This work offers a universal strategy to prepare a high-performance anti-fouling and antithrombosis coating, which is expected to promote the development of functional coatings for biomedical materials.

Simulation,construction and characterization of a multi-functional thrombolytic agent with anti-thrombosis activity

Prourokinase(scu-PA),a thrombolytic agent,was inserted between Gly118 and Ile119 with foreign anti-thrombosis functional motif(Lys-Gly-Asp-Trp-motif)to construct a multi-functional chimeric molecule.The molecular model of a chimera was simulated and pre-dicted.The recombinant chimeric protein was expressed by the baculovirus-insect cell expression system and puri-fied by affinity chromatography.The physico-chemical characteristics of the chimeric molecule were assayed.The thrombolytic activity was determined to be 90000 IU/mg of fibrinolytic special activity by the fibrin-plate method.The anti-thrombosis activities were also assayed with IC50 of 9.6 μM by an inhibition test of ADP-induced platelet aggregation.

The Antithrombotic Effects of P6A and its Derivatives

P6A was able to increase coronary blood flow and improve hemodynamics in the coronary thrombosis model of dogs In the binding of fibrinogen to GP IIb/IIIa,RGD is the key sequence In the present paper the effects of the coupling compounds of P6A and its derivatives,QP6A with RGDS,RGDV and RGDF were tested The effects of the coupling compounds so obtained on carotid thrombosis in rats were investigated At the dose of 5 μmol/kg,RGDS and RGDV exhibited no antithrombotic effects,whereas at 2.5μmol/kg RGDF decreased the dry-weight ofthrombus significantly On the other hand,P6A(5μmol/kg)and QP6A(2.5μmol/kg)showed significant antithrombosis activities.All of the coupling compounds,except P6A-RGDF and QP6A-RGDF,had potent antithrombosis effects.

Antithrombotic treatment strategy for patients with coronary artery ectasia and acute myocardial infarction: A case report

BACKGROUND There is no consensus on the antithrombotic treatment strategy for patients with coronary artery ectasia(CAE).CASE SUMMARY This case reports the dynamic observation of a patient for 48 mo after a diagnosis of CAE with acute myocardial infarction(AMI).The first antithrombotic agents used were aspirin(100 mg/d)and clopidogrel(75 mg/d).During the sixth month of observation,a second AMI occurred involving the same culprit vessel;therefore,antithrombotic agents were changed to aspirin(100 mg/d)and ticagrelor(90 mg twice per day).Twelve months after the second AMI,an attempt to reduce the dosage ticagrelor failed;therefore the original dose was continued.The CAE was relatively stable during the following 4 years.CONCLUSION This case indicates that a combination of aspirin and ticagrelor may be more effective for CAE patients with AMI than aspirin and clopidogrel.

Design, construction and characterization of prourokinase mutant engineered by introduction of special Lys-Gly-Asp-Trp-motif

A recombinant prourokinase chimera was constructed by introduction of Lys-Gly-Asp-Trp-motif between Gly118 and Ile119 among the kringle domain. The structure of designed protein was predicted and simulated. The recombinant prourokinase chimera was produced in insect cell sf9 with baculovirus-expression vector and existed as active form. Chimera protein was purified by affinity chromatography coupled with antibody. The special activity of the chimera was 90,000 IU/mg detected by fibrin plate determination. It was also shown that chimera inhibited ADP-induced platelet aggregation in a concentration depenent manner. These results showed the prourokinase chimera exhibited not only high fibrinolytic activity but also had anti-thrombosis function.

Nitric oxide-generating compound and bio-clickable peptide mimic for synergistically tailoring surface anti-thrombogenic and anti-microbial dual-functions

Application of extracorporeal circuits and indwelling medical devices has saved many lives.However,it is accompanied with two major complications:thrombosis and infection.To address this issue,we apply therapeutic nitric oxide gas(NO)and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual functions.Such functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)chelated copper ions(Cu-DOTA)and dibenzylcyclooctyne-(DBCO-)modified antimicrobial peptide based on carbodiimide and click chemistry respectively.The integration of peptide and Cu-DOTA grants the modified surface the ability to not only efficiently inhibit bacterial growth,but also catalytically generate NO from endogenous s-nitrosothiols(RSNO)to reduce adhesion and activation of platelets,preventing the formation of thrombus.We envision that the stepwise synergistic modification strategy by using anticoagulant NO and antibacterial peptide would facilitate the surface multifunctional engineering of extracorporeal circuits and indwelling medical devices,with reduced clinical complications associated with thrombosis and infection.

Preparation of phospholipid-based polycarbonate urethanes for potential applications of blood-contacting implants

Polyurethanes are widely used in interventional devices due to the excellent physicochemical property.However,non-specific adhesion and severe inflammatory response of ordinary polyurethanes may lead to severe complications of intravenous devices.Herein,a novel phospholipid-based polycarbonate urethanes(PCUs)were developed via two-step solution polymerization by direct synthesis based on functional raw materials.Furthermore,PCUs were coated on biomedical metal sheets to construct biomimetic anti-fouling surface.The results of stress–strain curves exhibited excellent tensile properties of PCUs films.Differential scanning calorimetry results indicated that the microphase separation of such PCUs polymers could be well regulated by adjusting the formulation of chain extender,leading to different biological response.In vitro blood compatibility tests including bovine serum albumin adsorption,fibrinogen adsorption and denaturation,platelet adhesion and whole-blood experiment showed superior performance in inhibition non-specific adhesion of PCUs samples.Endothelial cells and smooth muscle cells culture tests further revealed a good anti-cell adhesion ability.Finally,animal experiments including ex vivo blood circulation and subcutaneous inflammation animal experiments indicated a strong ability in anti-thrombosis and histocompatibility.These results high light the strong anti-adhesion property of phospholipid-based PCUs films,which may be applied to the blood-contacting implants such as intravenous catheter or antithrombotic surface in the future.