Prolonged patency of fully covered self-expandable metal stents with an externally anchored plastic stent in distal malignant biliary obstruction.

BACKGROUND : Fully covered self-expandable metal stents (FCSEMSs) are widely used for endoscopic treatment of distal malignant biliary obstruction (dMBO). We aimed to assess the efficacy of anchoring an external plastic stent to an FCSEMS in dMBO. METHODS : A multicenter retrospective cohort study was performed in patients with dMBO to compare stent patency between FCSEMSs and FCSEMSs with an externally anchored plastic stent (EPS). For external anchoring, a 7-Fr double-pigtail plastic stent (DPPS) was placed first in the bile duct, then an FCSEMS was deployed side-by-side. RESULTS : Among a total of 185 patients, 65 had an FCSEMS alone and 120 had an FCSEMS with an EPS. The median stent patency was significantly longer in the FCSEMS with an EPS group than in the FCSEMS only group (342 vs. 240 days; P = 0.04). The rate of stent migration was significantly lower in the FCSEMS with an EPS group than in the FCSEMS only group (10.8 % vs. 27.7 %; P = 0.01). There were no significant differences in the rates of stent occlusion and adverse events between the two groups. CONCLUSIONS : A novel and simple technique of anchoring an external plastic stent may decrease the risk of FCSEMS migration and prolong stent patency, without significantly increasing the adverse events rate in dMBO.

Efficacy of an internal anchoring plastic stent to prevent migration of a fully covered metal stent in malignant distal biliary strictures: a randomized controlled study.

BACKGROUND: Two types of self-expandable metal stents (SEMS) are available for malignant distal biliary obstruction: fully covered SEMS (FCSEMS) and uncovered SEMS. FCSEMS can prevent stent ingrowth, but a major concern is spontaneous migration. This study aimed to determine whether the additional insertion of a double-pigtail plastic stent to anchor the FCSEMS can prevent migration. METHODS: 68 patients with unresectable, malignant, distal, biliary obstruction were included in this multicenter, randomized, superiority trial. The patients were randomly assigned to receive either the FCSEMS plus an anchoring plastic stent (n = 33) or an FCSEMS alone (n = 35). After placement of the FCSEMS, the anchoring stent was inserted inside the FCSEMS. The primary outcome was the rate of stent migration during the 6-month follow-up. The secondary outcomes were stent-related adverse events, stent patency, and survival rates. RESULTS: The baseline characteristics were similar between the two groups. The rate of stent migration at 6 months was significantly lower in patients with the FCSEMS plus anchoring stent (15 % vs. 40 %; P = 0.02). The mean stent patency was significantly longer in the FCSEMS plus anchoring group (237 days [95 % confidence interval [CI] 199 to 275] vs. 173 days [95 %CI 130 to 217]; P = 0.048). There were no significant differences in stent-related adverse events and overall survival rates at 6 months between the two groups. CONCLUSIONS: Our data suggest that the additional double-pigtail plastic stent anchored the FCSEMS to prevent migration and prolonged patency without any serious adverse events.

Synergistic Effect of Detection and Separation for Pathogen Using Magnetic Clusters.

Early diagnosis of infectious diseases is important for treatment; therefore, selective and rapid detection of pathogenic bacteria is essential for human health. We report a strategy for highly selective detection and rapid separation of pathogenic microorganisms using magnetic nanoparticle clusters. Our approach to develop probes for pathogenic bacteria, including Salmonella, is based on a theoretically optimized model for the size of clustered magnetic nanoparticles. The clusters were modified to provide enhanced aqueous solubility and versatile conjugation sites for antibody immobilization. The clusters with the desired magnetic property were then prepared at critical micelle concentration (CMC) by evaporation-induced self-assembly (EISA). Two different types of target-specific antibodies for H- and O-antigens were incorporated on the cluster surface for selective binding to biological compartments of the flagella and cell body, respectively. For the two different specific binding properties, Salmonella were effectively captured with the O-antibody-coated polysorbate 80-coated magnetic nanoclusters (PCMNCs). The synergistic effect of combining selective targeting and the clustered magnetic probe leads to both selective and rapid detection of infectious pathogens.

HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers.

Hyaluronic Acid-Based Nanogels Produced by Microfluidics-Facilitated Self-Assembly Improves the Safety Profile of the Cationic Host Defense Peptide Novicidin.

PURPOSE: Cationic host defence peptides constitute a promising class of therapeutic drug leads with a wide range of therapeutic applications, including anticancer therapy, immunomodulation, and antimicrobial activity. Although potent and efficacious, systemic toxicity and low chemical stability have hampered their commercial development. To overcome these challenges a novel nanogel-based drug delivery system was designed. METHOD: The peptide novicidin was self-assembled with an octenyl succinic anhydride-modified analogue of hyaluronic acid, and this formulation was optimized using a microfluidics-based quality-by-design approach. RESULTS: By applying design-of-experiment it was demonstrated that the encapsulation efficiency of novicidin (15% to 71%) and the zeta potential (-24 to -57 mV) of the nanogels could be tailored by changing the preparation process parameters, with a maximum peptide loading of 36 ± 4%. The nanogels exhibited good colloidal stability under different ionic strength conditions and allowed complete release of the peptide over 14 days. Furthermore, self-assembly of novicidin with hyaluronic acid into nanogels significantly improved the safety profile at least five-fold and six-fold when tested in HUVECs and NIH 3T3 cells, respectively, whilst showing no loss of antimicrobial activity against Escherichia coli and Staphylococcus aureus. CONCLUSION: Formulation in nanogels could be a viable approach to improve the safety profile of host defence peptides.

3D printing modality effect: Distinct printing outcomes dependent on selective laser sintering (SLS) and melt extrusion.

A direct and comprehensive comparative study on different 3D printing modalities was performed. We employed two representative 3D printing modalities, laser- and extrusion-based, which are currently used to produce patient-specific medical implants for clinical translation, to assess how these two different 3D printing modalities affect printing outcomes. The same solid and porous constructs were created from the same biomaterial, a blend of 96% poly-ε-caprolactone (PCL) and 4% hydroxyapatite (HA), using two different 3D printing modalities. Constructs were analyzed to assess their printing characteristics, including morphological, mechanical, and biological properties. We also performed an in vitro accelerated degradation study to compare their degradation behaviors. Despite the same input material, the 3D constructs created from different 3D printing modalities showed distinct differences in morphology, surface roughness and internal void fraction, which resulted in different mechanical properties and cell responses. In addition, the constructs exhibited different degradation rates depending on the 3D printing modalities. Given that each 3D printing modality has inherent characteristics that impact printing outcomes and ultimately implant performance, understanding the characteristics is crucial in selecting the 3D printing modality to create reliable biomedical implants.

Synthesis of polymer-lipid nanoparticles for image-guided delivery of dual modality therapy.

For advanced treatment of diseases such as cancer, multicomponent, multifunctional nanoparticles hold great promise. In the current study we report the synthesis of a complex nanoparticle (NP) system with dual drug loading as well as diagnostic properties. To that aim we present a methodology where chemically modified poly(lactic-co-glycolic) acid (PLGA) polymer is formulated into a polymer-lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric core and an anti-angiogenic drug sorafenib (SRF) in the lipidic corona. The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In addition, a near-infrared (NIR) Cy7 dye was incorporated in the coating. To fabricate the NP we used a microfluidics-based technique that offers unique NP synthesis conditions, which allowed for encapsulation and fine-tuning of optimal ratios of all the NP components. NP phantoms could be visualized with computed tomography (CT) and near-infrared (NIR) fluorescence imaging. We observed timed release of the encapsulated drugs, with fast release of the corona drug SRF and delayed release of a core drug DOX. In tumor bearing mice intravenously administered NPs were found to accumulate at the tumor site by fluorescence imaging.

Mass production and size control of lipid-polymer hybrid nanoparticles through controlled microvortices.

Lipid-polymer hybrid (LPH) nanoparticles can deliver a wide range of therapeutic compounds in a controlled manner. LPH nanoparticle syntheses using microfluidics improve the mixing process but are restricted by a low throughput. In this study, we present a pattern-tunable microvortex platform that allows mass production and size control of LPH nanoparticles with superior reproducibility and homogeneity. We demonstrate that by varying flow rates (i.e., Reynolds number (30-150)) we can control the nanoparticle size (30-170 nm) with high productivity (∼3 g/hour) and low polydispersity (∼0.1). Our approach may contribute to efficient development and optimization of a wide range of multicomponent nanoparticles for medical imaging and drug delivery.

Acquisition of human alveolar bone-derived stromal cells using minimally irrigated implant osteotomy: in vitro and in vivo evaluations.

OBJECTIVES: Implant osteotomy yields a substantial amount of bone in the form of bone chips entrapped within drill flutes, and can provide a promising cell source for tissue engineering. The aims of this study were to isolate human alveolar bone-derived stromal cells (hABCs) obtained during implant osteotomy, and to evaluate osteogenic differentiation capacity of hABCs. MATERIAL AND METHODS: Bone chips were obtained by minimally irrigated implant drilling technique from 10 human donors. Isolated cells were studied with respect to their colony-forming efficiency, surface marker expression by immunofluorescence staining, fluorescence-activated cell sorting analysis and self-renewal potency. To verify the differentiation activity, in vitro osteogenic and adipogenic gene expressions were evaluated by reverse transcription-polymerase chain reaction, and in vitro formation of mineralized nodule and adipocytes was also evaluated. In vivo bone-forming activity was assessed by ectopic transplantation in immunocompromised mice (n = 5). RESULTS: Human alveolar bone-derived stromal cells population with characteristics of mesenchymal stem cells was present in the isolated cells. Upon hABC transplantation, significant ectopic bone formation was induced with the characteristics of fully matured bone tissue. CONCLUSION: The data support the feasibility of using hABCs as a source of stem cells for dentoalveolar bone tissue reconstruction. The cell source has an advantage that the hABCs can be easily acquired during implant surgery.

Maturation of alveolar bone following implantation of an rhGDF-5/PLGA composite into 1-wall intra-bony defects in dogs: 24-week histometric observations.

OBJECTIVE: The aim of this study was to evaluate long-term (24 weeks) alveolar bone maturation following surgical application of recombinant human growth/differentiation factor-5 (rhGDF-5) in an injectable poly-lactide-co-glycolide-acid (PLGA) composite carrier using an established periodontal defect model. METHODS: Routine, bilateral, 4 × 5 mm (width × depth), 1-wall, critical-size, intra-bony periodontal defects were surgically created at the 2nd and 4th mandibular premolar teeth in 10 Beagle dogs. The animals were randomized to receive (split-mouth design; defect sites in the same jaw quadrant getting the same treatment) rhGDF-5/PLGA high dose (188 µg/defect) versus sham-surgery control (5 animals), and rhGDF-5/PLGA low dose (37 µg/defect) versus carrier control (5 animals). The animals were euthanized for histometric analysis following a 24-week healing interval. RESULTS: Clinical healing was uneventful. The rhGDF-5 high dose significantly increased bone formation compared with controls in terms of bone area (p < 0.05), and a high degree of bone maturation was observed in the rhGDF-5/PLGA high dose group. Root resorption/ankylosis or other aberrant healing events were not observed. CONCLUSION: The rhGDF-5/PLGA appears to support alveolar bone healing/regeneration and the rhGDF-5/PLGA high dose uniquely increased maturation of the regenerated bone.

Piperazine-derived lipid nanoparticles deliver mRNA to immune cells in vivo.

In humans, lipid nanoparticles (LNPs) have safely delivered therapeutic RNA to hepatocytes after systemic administration and to antigen-presenting cells after intramuscular injection. However, systemic RNA delivery to non-hepatocytes remains challenging, especially without targeting ligands such as antibodies, peptides, or aptamers. Here we report that piperazine-containing ionizable lipids (Pi-Lipids) preferentially deliver mRNA to immune cells in vivo without targeting ligands. After synthesizing and characterizing Pi-Lipids, we use high-throughput DNA barcoding to quantify how 65 chemically distinct LNPs functionally delivered mRNA (i.e., mRNA translated into functional, gene-editing protein) in 14 cell types directly in vivo. By analyzing the relationships between lipid structure and cellular targeting, we identify lipid traits that increase delivery in vivo. In addition, we characterize Pi-A10, an LNP that preferentially delivers mRNA to the liver and splenic immune cells at the clinically relevant dose of 0.3 mg/kg. These data demonstrate that high-throughput in vivo studies can identify nanoparticles with natural non-hepatocyte tropism and support the hypothesis that lipids with bioactive small-molecule motifs can deliver mRNA in vivo.

Optimization of lipid nanoparticles for the delivery of nebulized therapeutic mRNA to the lungs.

Lipid nanoparticles (LNPs) for the efficient delivery of drugs need to be designed for the particular administration route and type of drug. Here we report the design of LNPs for the efficient delivery of therapeutic RNAs to the lung via nebulization. We optimized the composition, molar ratios and structure of LNPs made of lipids, neutral or cationic helper lipids and poly(ethylene glycol) (PEG) by evaluating the performance of LNPs belonging to six clusters occupying extremes in chemical space, and then pooling the lead clusters and expanding their diversity. We found that a low (high) molar ratio of PEG improves the performance of LNPs with neutral (cationic) helper lipids, an identified and optimal LNP for low-dose messenger RNA delivery. Nebulized delivery of an mRNA encoding a broadly neutralizing antibody targeting haemagglutinin via the optimized LNP protected mice from a lethal challenge of the H1N1 subtype of influenza A virus, and delivered mRNA more efficiently than LNPs previously optimized for systemic delivery. A cluster approach to LNP design may facilitate the optimization of LNPs for other administration routes and therapeutics.

Polymeric Nanoparticles Controlled by On-Chip Self-Assembly Enhance Cancer Treatment Effectiveness.

Nanoparticle (NP)-based drug delivery systems or nanomedicines have broadened the horizon of translational research for decades. Conventional bulk mixing synthesis methods have impeded successful clinical translations of nanomedicines due to the limited ability of the controlled, scalable production with high uniformity. Herein, an on-chip preparation of self-assembled, drug-encapsulated polymeric NPs is presented for their improved uniformity and homogeneity that results in enhanced anti-cancer effect in vitro and in vivo. The NPs are formulated through rapid convective mixing of two aqueous solutions of a hydrophilic polymer and an anti-cancer drug, doxorubicin (DOX), in the swirling microvortex reactor (SMR). Compared to conventional bulk-mixed NPs (BMPs), the microvortex-synthesized NPs (MVPs) exhibit narrower size distributions and better size tunability. It is found that the improved uniformity and homogeneity of the MVPs not only enhance cellular uptake and anti-cancer effect with pH-responsive drug release in vitro, but also result in an improved tumor regression and decreased side effects at off-targeted organs in vivo. The findings demonstrate that uniformly designed NPs with more homogeneous properties can induce a significant enhancement of an anti-cancer effect in vivo. The results show the potential of a high-speed on-chip synthesis as a scalable manufacturing platform for reliable clinical translations of nanomedicines.

Dynamics of individual polymers using microfluidic based microcurvilinear flow.

Polymer dynamics play an important role in a diversity of fields including materials science, physics, biology and medicine. The spatiotemporal responses of individual molecules such as biopolymers have been critical to the development of new materials, the expanded understanding of cell structures including cytoskeletal dynamics, and DNA replication. The ability to probe single molecule dynamics however is often limited by the availability of small-scale technologies that can manipulate these systems to uncover highly intricate behaviors. Advances in micro- and nano-scale technologies have simultaneously provided us with valuable tools that can interface with these systems including methods such as microfluidics. Here, we report on the creation of micro-curvilinear flow through a small-scale fluidic approach, which we have been used to impose a flow-based high radial acceleration ( approximately 10(3) g) on individual flexible polymers. We were able to employ this microfluidic-based approach to adjust and control flow velocity and acceleration to observe real-time dynamics of fluorescently labeled lambda-phage DNA molecules in our device. This allowed us to impose mechanical stimulation including stretching and bending on single molecules in localized regimes through a simple and straightforward technology-based method. We found that the flexible DNA molecules exhibited multimodal responses including distinct conformations and controllable curvatures; these characteristics were directly related to both the elongation and bending dynamics dictated by their locations within the curvilinear flow. We analyzed the dynamics of these individual molecules to determine their elongation strain rates and curvatures ( approximately 0.09 microm(-1)) at different locations in this system to probe the individual polymer structural response. These results demonstrate our ability to create high radial acceleration flow and observe real-time dynamic responses applied directly to individual DNA molecules. This approach may also be useful for studying other biologically based polymers including additional nucleic acids, actin filaments, and microtubules and provide a platform to understand the material properties of flexible polymers at a small scale.

A comparison of the Niti-D biliary uncovered stent and the uncovered Wallstent in malignant biliary obstruction.

BACKGROUND: The conformability of uncovered self-expandable metal stents (SEMSs) plays an important role in maintaining stent patency. However, whether increased conformability can prolong the duration of SEMS patency remains to be proved. OBJECTIVE: The aim of this study was to examine the efficacy and complication rates of the Niti-D biliary uncovered metal stent (NDS), which is more conformable than the uncovered Wallstent. DESIGN: Nonrandomized, retrospective study. SETTING: Tertiary-care academic medical center. PATIENTS: From March 2005 to July 2007, 101 patients received an NDS (41 cases) or a Wallstent (60 cases) for malignant biliary obstruction. INTERVENTIONS: SEMS placement. RESULTS: Stent occlusion occurred in 11 patients (26.8%) with the NDS and 17 patients (28.3%) with the Wallstent. The median duration of stent patency tended to be longer for the NDS group (153 days) than for the Wallstent group (124 days); however, the difference was not statistically significant (P = .204). The median duration of overall survival of patients was 160 days for the NDS and 148 days for the Wallstent. The subgroup analysis showed that 27 patients had hilar obstruction (NDS 13, Wallstent 14). The median duration of stent patency was 249 days for the NDS group and 76 days for the Wallstent group; this difference was statistically significant (P = .006). The complications included pancreatitis in 3 NDS cases and 5 Wallstent cases. LIMITATION: The absence of prospective randomized recruitment. CONCLUSION: The results of this study showed no significant differences between the NDS and the Wallstent for the palliative endoscopic management of malignant biliary obstruction. There were no significant differences in patency, complication rates, and patient survival between the more conformable NDS and the conventional Wallstent. However, the NDS, which has good conformability, may be preferred for hilar obstruction.

Step-wise endoscopic approach to palliative bilateral biliary drainage for unresectable advanced malignant hilar obstruction.

The ideal type of stent utilized at index endoscopic retrograde cholangiopancreatography (ERCP) in management of malignant hilar obstruction (MHO) remains unclear. We aimed to determine the ideal stent choice in patients with MHO. In this retrospective study, patients with unresectable MHO were separated into the plastic stent (PS) group and the self-expandable metal stent (SEMS) group. The primary outcome was the risk and rate of rescue percutaneous transhepatic biliary drainage (PTBD). The secondary outcomes were the progression-free survival, the overall survival and the PTBD-free period (days). Thirty-six patients in the PS group and 38 patients in the SEMS group were enrolled. The risk for PTBD was higher in SEMS group (HR = 2.205, 95% C.I. 0.977-4.977, P = 0.057). The rate of PTBD was significantly lower in the PS group. (22.2% vs 50.0%, P = 0.017) There were no differences in overall survival and progression-free survival (410 and 269 in the PS group, 395 and 266 in the SEMS group, P = 0.663 and P = 0.757). The PTBD-free period was significantly longer in the PS group. (836.43 vs 586.40, P = 0.039) Although comparable in clinical efficacy, utilization of PS at index ERCP may reduce patient's discomfort by avoiding PTBD and prolonging PTBD-free period in patients with MHO.

Development of a Shape-Memory Tube to Prevent Vascular Stenosis.

Inserting a graft into vessels with different diameters frequently causes severe damage to the host vessels. Poor flow patency is an unresolved issue in grafts, particularly those with diameters less than 6 mm, because of vessel occlusion caused by disturbed blood flow following fast clotting. Herein, successful patency in the deployment of an ≈2 mm diameter graft into a porcine vessel is reported. A new library of property-tunable shape-memory polymers that prevent vessel damage by expanding the graft diameter circumferentially upon implantation is presented. The polymers undergo seven consecutive cycles of strain energy-preserved shape programming. Moreover, the new graft tube, which features a diffuser shape, minimizes disturbed flow formation and prevents thrombosis because its surface is coated with nitric-oxide-releasing peptides. Improved patency in a porcine vessel for 18 d is demonstrated while occlusive vascular remodeling occurs. These insights will help advance vascular graft design.

Influence of Acid, Ethanol, and Anthocyanin Pigment on the Optical and Mechanical Properties of a Nanohybrid Dental Composite Resin.

This study investigated the influences of acidity, ethanol, and pigment on the optical properties, microhardness, and surface roughness (Ra) of a nanohybrid dental composite resin. A total of 108 disc-shaped specimens were fabricated using a nanohybrid dental composite and allocated into 36 different storage solutions according to the levels of pH (2.0, 3.0, 4.0, and 5.5), ethanol (0%, 20%, and 40%), and anthocyanin pigment (0%, 2.5%, and 12.5%). Measurements of the colorimetric parameter and the amount of color change (ΔE), translucency parameter (TP), microhardness, and surface roughness (Ra) were performed at 24 h (baseline), 1-, 2-, 3-, and 4-weeks. Repeated measures of analysis of variance (ANOVA) with a Tukey honestly significant difference test and Pearson correlation analysis were carried out (α = 0.05). Pigment of 12.5% or 40% ethanol significantly increased the ΔE (P < 0.001, P = 0.048, respectively). Pigment of 2.5% or 12.5% significantly decreased the TP (P = 0.001, P < 0.001, respectively). Microhardness of composite resin stored in pH 2.0, 3.0, 4.0 solution was lower than that for pH 5.5 (P < 0.001). Pigment, ethanol, and pH did not influence the Ra. TP change and ΔE, and Ra and ΔE had a significant positive correlation (P < 0.05). In conclusion, pigment and ethanol levels influenced the optical properties and acidity affected the microhardness of composite resin.

Robust manufacturing of lipid-polymer nanoparticles through feedback control of parallelized swirling microvortices.

A variety of therapeutic and/or diagnostic nanoparticles (NPs), or nanomedicines, have been formulated for improved drug delivery and imaging applications. Microfluidic technology enables continuous and highly reproducible synthesis of NPs through controlled mixing processes at the micro- and nanoscale. Yet, the inherent low-throughput remains a critical roadblock, precluding the probable applications of new nanomedicines for clinical translation. Here we present robust manufacturing of lipid-polymer NPs (LPNPs) through feedback controlled operation of parallelized swirling microvortex reactors (SMRs). We demonstrate the capability of a single SMR to continuously produce multicomponent NPs and the high-throughput performance of parallelized SMRs for large-scale production (1.8 kg d-1) of LPNPs while maintaining the physicochemical properties. Finally, we present robust and reliable manufacturing of NPs by integrating the parallelized SMR platform with our custom high-precision feedback control system that addresses unpredictable disturbances during the production. Our approach may contribute to efficient development and optimization of a wide range of multicomponent NPs for medical imaging and drug delivery, ultimately facilitating good manufacturing practice (GMP) production and accelerating the clinical translation.

Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity.

The leading cause of synthetic graft failure includes thrombotic occlusion and intimal hyperplasia at the site of vascular anastomosis. Herein, we report a co-immobilization strategy of heparin and potent anti-neointimal drug (Mitogen Activated Protein Kinase II inhibitory peptide; MK2i) by using a tyrosinase-catalyzed oxidative reaction for preventing thrombotic occlusion and neointimal formation of synthetic vascular grafts. The binding of heparin-tyramine polymer (HT) onto the polycarprolactone (PCL) surface enhanced blood compatibility with significantly reduced protein absorption (64.7% decrease) and platelet adhesion (85.6% decrease) compared to bare PCL surface. When loading MK2i, 1) the HT depot surface gained high MK2i-loading efficiency through charge-charge interaction, and 2) this depot platform enabled long-term, controlled release over 4weeks (92-272µg/mL of MK2i). The released MK2i showed significant inhibitory effects on VSMC migration through down-regulated phosphorylation of target proteins (HSP27 and CREB) associated with intimal hyperplasia. In addition, it was found that the released MK2i infiltrated into the tissue with a cumulative manner in ex vivo human saphenous vein (HSV) model. This present study demonstrates that enzymatically HT-coated surface modification is an effective strategy to induce long-term MK2i release as well as hemocompatibility, thereby improving anti-neointimal activity of synthetic vascular grafts.