Anti-platelet Adhesion Research Articles

Amphiphilic poly(methacryloxyethyl sulfobetaine)-block-poly(ε-caprolactone) blended polyvinyl chloride plastics: Study on the Relationship between molecular structure and antibiofouling properties

The blending of amphiphilic copolymers with plastics is an important method for preparing antibiofouling medical plastics. However, enhancing the enrichment of amphiphilic copolymers on the plastic surface, thereby improving the antibiofouling performance of the plastics remain challenging tasks. Herein, we designed and synthesized a series of amphphilic copolymers, denoted as PSB-b-nPCL. These copolymers possess similar chemical compositions but exhibit distinct topological structures. Antibiofouling flexible polyvinyl chloride (PVC) films were prepared by blending PSB-b-nPCL with PVC. These films showed excellent mechanical and thermal properties. X-ray photoelectron spectroscopy, water contact angle and hydration capacity tests demonstrated that PSB-b-nPCL which bearing more PCL blocks were more prone to migrating to the film surface, thereby enhancing the film’s hydrophilicity. Furthermore, anti-protein adsorption, anti-bacterial and anti-platelet adhesion properties of the films were investigated. It was found that topological structure can obviously affect the antibiofouling performance of films. Specifically, films blended with PSB-b-nPCL containing more PCL blocks exhibited superior performance. The optimal blended film achieved a reduction of 96.4% in bovine albumin adsorption, 82% in platelet adhesion, and nearly complete inhibition of bacterial adhesion. We anticipate that the strategy presented in this work will pave a new path for the development of high performance antibiofouling plastics.

Fabrication of an Antibacterial/Anticoagulant Dual-Functional Surface for Left Ventricular Assist Devices via Mussel-Inspired Polydopamine Chemistry.

Infections and thrombosis remain unsolved problems for implanted cardiovascular devices, such as left ventricular assist devices. Hence, the development of surfaces with improved blood compatibility and antimicrobial properties is imperative to reduce complications after artificial heart implantation. In this work, we report a novel approach to fabricate multifunctional surfaces for left ventricular transplanted ventricular assist devices (LVADs) by immobilizing nitric oxide (NO) generation catalysts and heparin and reducing silver nanoparticles in situ. The general view, structure, and chemical compositions of the pure/modified surfaces were characterized using digital imaging, scanning electron microscope (SEM), atomic force microscope (AFM), water contact angle (WCA), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma (ICP). All of the results demonstrated that the AgNPs and heparin were successfully immobilized on the surface. The Cu ions and NO release experimental results showed that the immobilized copper ions could catalyze the production of NO from S-nitrosothiols within the biological system. Meanwhile, due to the synergistic anticoagulant effect of NO and surface-immobilized heparin, the fabricated modified surfaces exhibited antiplatelet adhesion activities and good hemocompatibility. Finally, the antimicrobial activity of the samples was evaluated by Escherichia coli and Staphylococcus aureus, and cytocompatibility was measured using human umbilical vein endothelial cells (HUVECs). The results demonstrated that silver nanoparticles (AgNPs) immobilized by surface reduction reaction did not cause any significant inhibition of cell proliferation while providing stable and effective antimicrobial properties. We envision that this simple surface modification strategy with bifunctional activities of antimicrobial and anticoagulant will find widespread use in clinically used indwelling left ventricular assist devices.

Customized Vascular Repair Microenvironment: Poly(lactic acid)-Gelatin Nanofibrous Scaffold Decorated with bFGF and Ag@Fe3O4 Core-Shell Nanowires.

Vascular defects caused by trauma or vascular diseases can significantly impact normal blood circulation, resulting in serious health complications. Vascular grafts have evolved as a popular approach for vascular reconstruction with promising outcomes. However, four of the greatest challenges for successful application of small-diameter vascular grafts are (1) postoperative anti-infection, (2) preventing thrombosis formation, (3) utilizing the inflammatory response to the graft to induce tissue regeneration and repair, and (4) noninvasive monitoring of the scaffold and integration. The present study demonstrated a basic fibroblast growth factor (bFGF) and oleic acid dispersed Ag@Fe3O4 core-shell nanowires (OA-Ag@Fe3O4 CSNWs) codecorated poly(lactic acid) (PLA)/gelatin (Gel) multifunctional electrospun vascular grafts (bAPG). The Ag@Fe3O4 CSNWs have sustained Ag+ release and exceptional photothermal capabilities to effectively suppress bacterial infections both in vitro and in vivo, noninvasive magnetic resonance imaging (MRI) modality to monitor the position of the graft, and antiplatelet adhesion properties to promise long-term patency. The gradually released bFGF from the bAPG scaffold promotes the M2 macrophage polarization and enhances the recruitment of macrophages, endothelial cells (ECs) and fibroblast cells. This significant regulation of diverse cell behavior has been proven to be beneficial to vascular repair and regeneration both in vitro and in vivo. Therefore, this study supplies a method to prepare multifunctional vascular-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for vascular tissue engineering.

Fabrication of metal-organic frameworks containing Cu2+ coated medical PVC catheters with durable antiplatelet and antibacterial activities

Polyvinyl chloride (PVC) catheters are widely used in medical environments especially in blood-contacting devices. In this study, a copper containing MOF material was coated on a PVC catheter to endow it with antiplatelet adhesion and antibacterial activity for potential clinical applications. The immobilization of the coordination polymer containing Cu2+ (Cu-MOF) on the inner surface of PVC catheters was carried out using a bioinspired coating combined with a layer-by-layer self-assembly strategy. Characterization of the Cu-MOF modified surfaces was confirmed using micro-infrared spectroscopy (MIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and water contact angle measurements (WCA). The resultant modified surfaces significantly reduced non-specific adsorption to model proteins with excellent anti-biofouling activity, as well as significantly inhibited the platelet adhesion and activation with superior antiplatelet activity. In vitro whole blood circulation test using a peristaltic pump also showed good antithrombotic properties. Besides, the Cu-MOF modified surfaces exhibited good hemocompatibility (hemolysis ratio < 5 %) and excellent antibacterial activity (approximately 97 % against S. auerus and E. coli). This study develops a simple and effective method for the surface modification of medical PVC catheter as potential blood-contacting biomaterials.

Peripheral vascular bioresorbable scaffolds: Past, present, and future

As peripheral vascular disease affects more and more people in the world, interventional treatment of peripheral blood vessels evolves from percutaneous transluminal angioplasty to bioresorbable vascular scaffolds (BVS). At present, the materials of peripheral vascular bioresorbable scaffolds mainly include polymers and metal materials, and have achieved certain clinical application effects. Examples of these BVS are provided, and their advantages and defects are discussed. Poly-L-lactic acid is most commonly used in polymer BVS. There have been some polymer BVS entering clinical research for peripheral blood vessels since the 10 s, and have various outcomes. Metal materials for BVS mainly include magnesium alloy, iron alloy, and zinc alloy. The improved magnesium alloy BVS show excellent antiplatelet adhesion ability and can reduce the formation of acute stent thrombosis in clinical research. The iron alloy BVS and zinc alloy BVS also show excellent performance in animal experiments. The drug coating of BVS is expected to be improved. Finally, prospects of future development are highlighted. With the continuous improvement of manufacturing and drug-coating process, their therapeutic effect is expected to continue to improve.

Cell adhesion behavior of poly(l‐lactide‐co‐glycolide)‐poly(1,5‐dioxepan‐2‐one) random multiblock copolymers

AbstractAlthough bioabsorbable polymers are promising implant materials, implanting hydrophobic polymers induces platelet adhesions and subsequent thrombus formation. We recently reported that a multiblock copolymer composed of poly(l‐lactide‐co‐glycolide) (PLGA) and poly(1,5‐dioxepan‐2‐one) (PDXO) exhibited antiplatelet adhesive behavior. In this study, the cell adhesion behaviors of PLGA and PDXO random multiblock copolymers (PLGA−PDXO RMBCs) were examined. All the RMBCs showed antiplatelet adhesion behavior, and the copolymers containing 40 or 51 mol% of the PDXO component showed good antiplatelet adhesive behavior. Good culture behavior was observed for HeLa cells, but human umbilical vein endothelial cells (HUVECs) proliferation was poor on PLGA−PDXO RMBC surfaces. The cell attachment inhibition studies revealed that both integrin‐dependent and integrin‐independent interactions worked for HeLa cell culture, whereas only integrin‐dependent interactions played an important role for HUVEC culture proliferation on copolymer surfaces. The findings of this study revealed the unique cell‐selective adhesion behavior of PDXO containing multiblock polymers—being nonadhesive to platelets and HUVECs, and adhesive to HeLa cells.

Bioinspired chitosan based functionalization of biomedical implant surfaces for enhanced hemocompatibility, antioxidation and anticoagulation potential: an in silico and in vitro study.

Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger activation of multiple reactive mechanisms including coagulation cascade and potentially causing serious adverse clinical events like late thrombosis. Active ingredients from natural sources including Foeniculum vulgare, Angelica sinensis, and Cinnamomum verum have the ability to inhibit the coagulation cascade and thrombus formation around biomedical implants. These properties are of interest for the development of a novel drug for biomedical implants to potentially solve the current blood clotting and coagulation problems which lead to stent thrombosis. The objective of this study was to incorporate different anticoagulants from natural sources into a degradable matrix of chitosan with varying concentrations ranging from 5% to 15% and a composite containing all three drugs. The presence of anticoagulant constituents was identified using GC-MS. Subsequently, all the compositions were characterized principally by using Fourier transform infrared spectroscopy and scanning electron microscopy while the drug release profile was determined using UV-spectrometry for a 30 days immersion period. The results indicated an initial burst release which was subsequently followed by the sustained release pattern. Compared to heparin loaded chitosan, DPPH and hemolysis tests revealed better blood compatibility of natural drug loaded films. Moreover, the anticoagulation activity of natural drugs was equivalent to the heparin loaded film; however, through docking, the mechanism of inhibition of the coagulation cascade of the novel drug was found to be through blocking the extrinsic pathway. The study suggested that the proposed drug composite expresses an optimum composition which may be a practicable and appropriate candidate for biomedical implant coatings.

Dragging 3D printing technique controls pore sizes of tissue engineered blood vessels to induce spontaneous cellular assembly

To date, several off-the-shelf products such as artificial blood vessel grafts have been reported and clinically tested for small diameter vessel (SDV) replacement. However, conventional artificial blood vessel grafts lack endothelium and, thus, are not ideal for SDV transplantation as they can cause thrombosis. In addition, a successful artificial blood vessel graft for SDV must have sufficient mechanical properties to withstand various external stresses. Here, we developed a spontaneous cellular assembly SDV (S-SDV) that develops without additional intervention. By improving the dragging 3D printing technique, SDV constructs with free-form, multilayers and controllable pore size can be fabricated at once. Then, The S-SDV filled in the natural polymer bioink containing human umbilical vein endothelial cells (HUVECs) and human aorta smooth muscle cells (HAoSMCs). The endothelium can be induced by migration and self-assembly of endothelial cells through pores of the SDV construct. The antiplatelet adhesion of the formed endothelium on the luminal surface was also confirmed. In addition, this S-SDV had sufficient mechanical properties (burst pressure, suture retention, leakage test) for transplantation. We believe that the S-SDV could address the challenges of conventional SDVs: notably, endothelial formation and mechanical properties. In particular, the S-SDV can be designed simply as a free-form structure with a desired pore size. Since endothelial formation through the pore is easy even in free-form constructs, it is expected to be useful for endothelial formation in vascular structures with branch or curve shapes, and in other tubular tissues such as the esophagus.

Construction of ZnONRs-PDA/PMPC nanocomposites on the surface of magnesium alloy with enhanced corrosion resistance and antibacterial performances

Magnesium alloy (MgA) with satisfactory biodegradability and excellent mechanical properties has been widely applied in new degradable medical implant materials, especially cardiovascular scaffold materials. However, fast degradation and limited biological activities always restrict the application of MgA. Herein, we have constructed multi-functional inorganic-organic nanocomposites (ZnONRs-PDA/PMPC) onto the surface of micro-arc oxidation pretreated magnesium alloys (MgA-MgO), where ZnO nanorods (ZnONRs) were grown by a microwave-assisted hydrothermal method, and polydopamine/poly(2-methacryloyloxyethyl phosphorylcholine) (PDA/PMPC) films were prepared by a co-deposition strategy. The morphology and composition of MgA-MgO-ZnONRs-PDA/PMPC were characterized by field emission-scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD), and so on. The MgA-MgO-ZnONRs-PDA/PMPC exhibited good hydrophilic property with a water contact angle of 37.4° and improved the corrosion resistance performance with decreasing the corrosion current density (icorr) by 3 orders of magnitude compared with pristine MgA. Moreover, the MgA-MgO-ZnONRs-PDA/PMPC showed good anti-platelet adhesion performance and excellent antibacterial activities with bactericidal rates of 98.1% against S. aureus and 96.2% against E. coli. This work provides an easy and effective method to fabricate a multi-functional nanocomposite with excellent corrosion resistance and biological activities that would facilitate the potential applications of MgA in biomedical fields.

Zwitterionic coating assisted by dopamine with metal-phenolic networks loaded on titanium with improved biocompatibility and antibacterial property for artificial heart.

Introduction: Titanium (Ti) and Ti-based alloy materials are commonly used to develop artificial hearts. To prevent bacterial infections and thrombus in patients with implanted artificial hearts, long-term prophylactic antibiotics and anti-thrombotic drugs are required, and this may lead to health complications. Therefore, the development of optimized antibacterial and antifouling surfaces for Ti-based substrate is especially critical when designing artificial heart implants. Methods: In this study, polydopamine and poly-(sulfobetaine methacrylate) polymers were co-deposited to form a coating on the surface of Ti substrate, a process initiated by Cu2+ metal ions. The mechanism for the fabrication of the coating was investigated by coating thickness measurements as well as Ultraviolet-visible and X-ray Photoelectron (XPS) spectroscopy. Characterization of the coating was observed by optical imaging, scanning electron microscope (SEM), XPS, atomic force microscope (AFM), water contact angle and film thickness. In addition, antibacterial property of the coating was tested using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as model strains, while the material biocompatibility was assessed by the antiplatelet adhesion test using platelet-rich plasma and in vitro cytotoxicity tests using human umbilical vein endothelial cells and red blood cells. Results and discussion: Optical imaging, SEM, XPS, AFM, water contact angle, and film thickness tests demonstrated that the coating was successfully deposited on the Ti substrate surface. The biocompatibility and antibacterial assays showed that the developed surface holds great potential for improving the antibacterial and antiplatelet adhesion properties of Ti-based heart implants.

Simultaneous deposition of tannic acid derivative and covalent conjugation of poly(2-methyl-2-oxazoline) for the construction of antifouling coatings

Bacterial adhesion and subsequent colonization play an important role in the failure of biomedical implants and devices. Thus, development of a simple surface modification strategy to combat bacterial adhesion is highly desirable. In this work, “one-pot” fabrication of antifouling coatings based on simultaneous surface adhesion of trihydroxyphenyl and dihydroxyphenyl moieties of tannic acid (TA) derivative and covalent conjugation of hydrophilic poly(2-methyl-2-oxazoline) (PMOXA) was demonstrated. Surface co-depositions of TA/PMOXA hybrids of different TA derivative to PMOXA weight ratios and different molecular weights of PMOXA were conducted. The surface hydrophilicity and deposition universality on various substrates were investigated. The anti-bacterial and anti-platelet adhesion, as well as anti-biofilm formation abilities, of the TA/PMOXA-based coating were also studied. In vitro hemolysis and cytotoxicity, and in vivo biocompatibility of the TA/PMOXA-based coating were further evaluated. All the results indicate that the TA/PMOXA-based coating could be employed as an antifouling additive on biomedical implants and devices.

Influence of Spin Coating and Dip Coating with Gelatin/Hydroxyapatite for Bioresorbable Mg Alloy Orthopedic Implants: In Vitro and In Vivo Studies.

Suitable biomechanical properties, good biocompatibility, and osteoconductivity of a degradable magnesium (Mg) alloy make it a potential material for orthopedic implants. The main limitation of Mg is its high corrosion rate in the human body. Surface modification is necessary to improve the Mg corrosion resistance. In this work, a polymeric layer of gelatin/nanohydroxyapatite (Gel/nHA) was coated on a ZK60 Mg alloy by dip coating and spin coating to test the corrosion resistance and biocompatibility in vitro and in vivo. The results from the in vitro test revealed that the coated groups reduced the corrosion rate with the corrosion current density by 59 and 81%, from 31.22 to 12.83 μA/cm2 and 5.83 μA/cm2 in the spin coating and dip coating groups, respectively. The dip coating group showed better corrosion resistance than the spin coating group with the lowest released hydrogen content (17.5 mL) and lowest pH value (8.23) and reducing the current density by 45%. In vitro, the relative growth rate was over 75% in all groups tested with MG63, demonstrating that the Mg substrate and coating materials were within the safety range. The dip coating and spin coating groups enhanced the cell proliferation with significantly higher OD values (3.3, 3.0, and 2.5, respectively) and had better antihemolysis and antiplatelet adhesion abilities than the uncoated group. The two coating methods showed no difference in the cellular response, cell migration, hemolysis, and platelet adhesion test. In in vivo tests in rats, the dip coating group also showed a higher corrosion resistance with a lower corrosion rate and mass loss than the spin coating group. In addition, the blood biochemistry and histopathology results indicated that all materials used in this study were biocompatible with living subjects. The present research confirmed that the two methods have no noticeable difference in cell and organ response but the corrosion resistance of dip coating was higher than that of spin coating either in vitro or in vivo.

Preparation and performance of random- and oriented-fiber membranes with core-shell structures via coaxial electrospinning.

The cells and tissue in the human body are orderly and directionally arranged, and constructing an ideal biomimetic extracellular matrix is still a major problem to be solved in tissue engineering. In the field of the bioresorbable vascular grafts, the long-term functional prognosis requires that cells first migrate and grow along the physiological arrangement direction of the vessel itself. Moreover, the graft is required to promote the formation of neointima and the development of the vessel walls while ensuring that the whole repair process does not form a thrombus. In this study, poly (l-lactide-co-ε-caprolactone) (PLCL) shell layers and polyethylene oxide (PEO) core layers with different microstructures and loaded with sodium tanshinone IIA sulfonate (STS) were prepared by coaxial electrospinning. The mechanical properties proved that the fiber membranes had good mechanical support, higher than that of the human aorta, as well as great suture retention strengths. The hydrophilicity of the oriented-fiber membranes was greatly improved compared with that of the random-fiber membranes. Furthermore, we investigated the biocompatibility and hemocompatibility of different functional fiber membranes, and the results showed that the oriented-fiber membranes containing sodium tanshinone IIA sulfonate had an excellent antiplatelet adhesion effect compared to other fiber membranes. Cytological analysis confirmed that the functional fiber membranes were non-cytotoxic and had significant cell proliferation capacities. The oriented-fiber membranes induced cell growth along the orientation direction. Degradation tests showed that the pH variation range had little change, the material mass was gradually reduced, and the fiber morphology was slowly destroyed. Thus, results indicated the degradation rate of the oriented-fiber graft likely is suitable for the process of new tissue regeneration, while the random-fiber graft with a low degradation rate may cause the material to reside in the tissue for too long, which would impede new tissue reconstitution. In summary, the oriented-functional-fiber membranes possessing core-shell structures with sodium tanshinone IIA sulfonate/polyethylene oxide loading could be used as tissue engineering materials for applications such as vascular grafts with good prospects, and their clinical application potential will be further explored in future research.

Nanofibrous polytetrafluoroethylene/poly(ε-caprolactone) membrane with hierarchical structures for vascular patch.

With the prevalence of cardiovascular diseases, developing cardiovascular supplements is becoming increasingly urgent. The ability of cells to rapidly adhere and proliferate to achieve endothelialization is extremely important for vascular grafts. In this work, we electrospun polytetrafluoroethylene (PTFE) nanofibrous membranes and used induced crystallization to manufacture poly(ε-caprolactone) (PCL) shish-kebab microstructures on PTFE nanofibers to overcome the inertness of PTFE, and promote cell adhesion and proliferation. PCL lamella periodically grew on the surface of PTFE nanofibers yielding a hierarchical structure, which improved the biocompatibility and mechanical properties of the PTFE nanofibrous membrane. The deposition of PCL lamella improved the hydrophilicity of electrospun PTFE nanofibers membrane, leading to good cell proliferation and adhesion. Also, due to the surface inertness of the substrate material PTFE, this PTFE/PCL composite film has good anti-platelet adhesion properties. Furthermore, cell proliferation could be regulated by controlling the integrity of the PCL crystal network. The vascular patch showed similar mechanical properties to natural blood vessels, providing a new strategy for vascular tissue engineering.

Chitosan-Heparin Polyelectrolyte Multilayer-Modified Poly(vinyl alcohol) Vascular Patches based on a Decellularized Scaffold for Vascular Regeneration.

Vascular patches play an important role in vascular reparation and cardiovascular diseases therapy. Recently, decellularized scaffold (DCS)-based vascular patches have drawn attention for their good biocompatibility and blood compatibility. In this work, we developed a poly(vinyl alcohol)-coated DCS as a vascular patch for vascular regeneration. Polyelectrolyte multilayers (PEMs) were further decorated on the surface via layer-by-layer (LbL) self-assembly to improve the biocompatibility of the vascular patch. According to the in vitro experiment, the vascular patch exhibited rapid endothelialization and good hemocompatibility. Compared with unmodified poly(vinyl alcohol)/DCS, the PEM-modified vascular patch possesses improved hemocompatibility, for example, enhanced anti-platelet adhesion ability, prolonged in vitro coagulation time, and decreased hemolysis rate. Therefore, this vascular patch is conducive to the proliferation and attachment of endothelial progenitor cells. Meanwhile, the in vivo performance in a porcine model was investigated with the in vivo computed tomography angiography and B ultrasound was used to further confirm the vascular regeneration. Excitedly, the porcine artery could remain unblocked for 5 months after implantation. Our current research provides a potential strategy for treating diseased blood vessels in clinical surgery.

Papaverine Infusion Through Aortic Root before Cardiac Self-recovery in Heart Valve Replacement with TiO2 Nanocrystalline Film Material.

This work was to investigate TiO2 nanocrystalline film material in heart valve replacement (HVR) and the effect of papaverine infusion through the aortic root before cardiac self-recovery during the HVR. TiO2 nanocrystalline films were prepared by radio frequency (RF) reactive sputtering. The crystallization characteristics and surface morphology of TiO2 nanocrystalline films were observed by X-ray diffraction and scanning electron microscopy, and the anti-platelet adhesion and anti-coagulation properties of the films were analyzed. 86 patients with heart valve disease were selected and all underwent HVR. They were randomly divided into a control group (routine treatment) and an experimental group (papaverine perfusion through aortic root), with 43 cases in each group. The rate of cardiac self-recovery and the dosage of dopamine were observed. The results showed that the TiO2 nanocrystalline film was composed of a large number of uniform particles, and the average particle size was about 18.97 ± 7.28 nm. The rate of cardiac self-recovery in the experimental group was 97.67%, which was significantly higher than that in the control group (67.44%) (P< 0.05). The dosage of epinephrine, dopamine, and duration of cardiopulmonary bypass (CPB) assistance in the observation group were less than those in the control group (P < 0.05). These results indicated that TiO2 nanocrystalline film could be used in HVR, and papaverine infusion through aortic root before HVR and myocardial protection measures can significantly improve the rate of cardiac self-recovery and promote postoperative recovery.

Crosslinking of dialdehyde heparin: a new strategy for improving the anticoagulant properties of porcine acellular dermal matrix.

The anticoagulant properties of valve materials are essential to maintain blood patency after artificial valve implantation. Porcine acellular dermal matrix (pADM) has low immunogenicity, good biocompatibility, and can reduce calcification by eliminating heterogeneous cells. However, its main component is collagen, which has strong coagulation function and poor anticoagulant activity. When used in heart valve materials, it can easily coagulate and form a life-threatening thrombus. Therefore, it is necessary to improve its anticoagulant performance. The glutaraldehyde (GA) cross-linked valves widely used clinically are easy to calcify with poor anticoagulant performance and cytotoxicity. In this study, dialdehyde heparin containing cross-linking active aldehyde groups was prepared by sodium periodate oxidation, then it was used for crosslinking with pADM to chemically modify its anticoagulant performance. Compared with GA cross-linked pADM (GA-pA), dialdehyde heparin cross-linked pADM (OL-pA) has better thermal stability and biocompatibility, especially its anticoagulant and antiplatelet adhesion were significantly improved, which can reduce the incidence of coagulation, thrombocytopenia and bleeding. In summary, dialdehyde heparin is expected to be applied to modify the anticoagulant properties of pADM and has great potential for the preparation and clinical application of anticoagulant materials such as heart valves and artificial blood vessels.

Electrochemical behavior, biocompatibility and mechanical performance of biodegradable iron with PEI coating.

Coating of the biodegradable metals represents an effective way of modification of their properties. Insufficient biological, mechanical, or degradation performance of pure metals may be enhanced when the proper type of organic polymer coating is used. In our previous work, the significant effect of the polyethyleneimine (PEI) coating not only on the rate but also on the type of corrosion was discovered. To bring a comprehensive overview of the Fe-PEI system performance, iron-based biodegradable scaffolds with polyethyleneimine coating were studied and their cytocompatibility and hemocompatibility, and mechanical properties were evaluated and discussed in this work. Electrochemical impedance spectroscopy (EIS) measurements were conducted for further study of material behavior. Biological analyses (MTS assay, fluorescent imaging, hemocompatibility tests) showed better cell proliferation on the surface of Fe-PEI samples but not sufficient overall cytocompatibility. Good anti-platelet adhesion properties but higher hemolysis when compared to the pure iron was also observed for the coated samples. Mechanical properties of the prepared Fe-PEI material were enhanced after coating. These findings suggest that the Fe-PEI may be an interesting potential biomaterial after further composition optimization resulting in lower cytotoxicity and better hemocompatibility.

Fabrication of a Porous Three-Dimensional Scaffold with Interconnected Flow Channels: Co-Cultured Liver Cells and In Vitro Hemocompatibility Assessment

The development of large-scale human liver scaffolds equipped with interconnected flow channels in three-dimensional space offers a promising strategy for the advancement of liver tissue engineering. Tissue-engineered scaffold must be blood-compatible to address the demand for clinical transplantable liver tissue. Here, we demonstrate the construction of 3-D macro scaffold with interconnected flow channels using the selective laser sintering (SLS) fabrication method. The accuracy of the printed flow channels was ensured by the incorporation of polyglycolic acid (PGA) microparticles as porogens over the conventional method of NaCl salt leaching. The fabricated scaffold was populated with Hep G2, followed by endothelization with endothelial cells (ECs) grown under perfusion of culture medium for up to 10 days. The EC covered scaffold was perfused with platelet-rich plasma for the assessment of hemocompatibility to examine its antiplatelet adhesion properties. Both Hep G2-covered scaffolds exhibited a markedly different albumin production, glucose metabolism and lactate production when compared to EC-Hep G2-covered scaffold. Most importantly, EC-Hep G2-covered scaffold retained the antiplatelet adhesion property associated with the perfusion of platelet-rich plasma through the construct. These results show the potential of fabricating a 3-D scaffold with interconnected flow channels, enabling the perfusion of whole blood and circumventing the limitation of blood compatibility for engineering transplantable liver tissue.

Improved Antithrombogenicity of a Poly(lactic acid) Surface Grafted with Chondroitin Sulfate.

For bioabsorbable vascular scaffolds (BVS), thrombosis is an important clinical problem. Poly(lactic acid) (PLA), as a commonly used manufacturing material of BVS, is always facing thrombosis events in the early stage of BVS implantation, because of a lack of anticoagulant properties. Herein, we introduced carboxyl functional groups on the surface of PLA by photooxidation modification and then used NH2-PEG-NH2 as an intermediate to graft chondroitin sulfate (CS) onto PLA. Fourier transform infrared spectroscopy was used to verify the success of each step of the modification, and X-ray photoelectron spectroscopy was used as a further supplement. The methyl of PLA was oxidized to carboxyl by photooxidation, and the hydrophilicity of PLA surface was improved. CS made endothelial cells better adhere to PLA and resisted the adhesion of platelets. The results showed that the surface of PLA grafted with CS embodies the advantages of promoting endothelial cell adhesion and antiplatelet adhesion, providing a broader application prospect for the application of PLA in BVS.