Functional Drug Delivery Research Articles

Core-Shell Structured Theranostics

Cancer threatens the life and well-being of human beings. Millions of newly diagnosed cancer cases and a large number of deaths caused by cancer are reported each year in the world. Early detection and effective treatment are key to reduce cancer mortality, which can be potentially realized by using “theranostics”. Theranostics are a group of hybrid nanoparticles that perform in cancer patients to provide both diagnostic and therapeutic functions through a single nano-sized structure. In particular, core-shell structured theranostics have shown unique physicochemical properties, allowing them to facilitate molecular/cell targeting, bio-imaging, and drug delivery functions. This review, therefore, aims to present and discuss the recent development of research on core-shell structured theranostics. Specifically, it focuses on core-shell structured theranostics made of metals, silica and polymers. Different aspects, such as synthesis and structure, of core-shell structured theranostics are discussed in this review. This review helps readers to have a good understanding of the design and fabrication of core-shell structured theranostics.

Electrospun core-shell nanofibers with encapsulated enamel matrix derivative for guided periodontal tissue regeneration.

The osteogenic effect of a composite electrospun core-shell nanofiber membrane encapsulated with Emdogain® (EMD) was evaluated. The membrane was developed through coaxial electrospinning using polycaprolactone as the shell and polyethylene glycol as the core. The effects of the membrane on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) were examined using Alizarin Red S staining and qRT-PCR. Characterization of the nanofiber membrane demonstrated core-shell morphology with a mean diameter of ~1 µm. Examination of the release of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) from core-shell nanofibers over a 22-day period showed improved release profile of encapsulated proteins as compared to solid nanofibers. When cultured on EMD-containing core-shell nanofibers, PDLSCs showed significantly improved osteogenic differentiation with increased Alizarin Red S staining and enhanced osteogenic gene expression, namely OCN, RUNX2, ALP, and OPN. Core-shell nanofiber membranes may improve outcomes in periodontal regenerative therapy through simultaneous mechanical barrier and controlled drug delivery function.

Polymeric Composite Matrix with High Biobased Content as Pharmaceutically Relevant Molecular Encapsulation and Release Platform.

Drug delivery systems (DDS) that can temporally control the rate and extent of release of therapeutically active molecules find applications in many clinical settings, ranging from infection control to cancer therapy. With an aim to design a locally implantable, controlled-release DDS, we demonstrated the feasibility of using cellulose nanocrystal (CNC)-reinforced poly (l-lactic acid) (PLA) composite beads. The performance of the platform was evaluated using doxorubicin (DOX) as a model drug for applications in triple-negative breast cancer. A facile, nonsolvent-induced phase separation (NIPS) method was adopted to form composite beads. We observed that CNC loading within these beads played a critical role in the mechanical stability, porosity, water uptake, diffusion, release, and pharmacological activity of the drug from the delivery system. When loaded with DOX, composite beads significantly controlled the release of the drug in a pH-dependent pattern. For example, PLA/CNC beads containing 37.5 wt % of CNCs showed a biphasic release of DOX, where 41 and 82% of the loaded drug were released at pH 7.4 and pH 5.5, respectively, over 7 days. Drug release followed Korsmeyer's kinetics, indicating that the release mechanism was mostly diffusion and swelling-controlled. We showed that DOX released from drug-loaded PLA/CNC composite beads locally suppressed the growth and proliferation of triple-negative breast cancer cells, MBA-MB-231, via the apoptotic pathway. The efficacy of the DDS was evaluated in human tissue explants. We envision that such systems will find applications for designing biobased platforms with programmed stability and drug delivery functions.

Biotinylated chitosan macromolecule based nanosystems: A review from chemical design to biological targets

World Health Organization estimates that 30–50% of cancers are preventable by healthy lifestyle choices, early detection and adequate therapy. When the conventional therapeutic strategies are still regulated by the lack of selectivity, multidrug resistance and severe toxic side effects, nanotechnology grants a new frontier for cancer management since it targets cancer cells and spares healthy tissues. This review highlights recent studies using biotin molecule combined with functional nanomaterials used in biomedical applications, with a particular attention on biotinylated chitosan-based nanosystems. Succinctly, this review focuses on five areas of recent advances in biotin engineering: (a) biotin features, (b) biotinylation approaches, (c) biotin functionalized chitosan based nanosystems for drug and gene delivery functions, (d) diagnostic and theranostic perspectives, and (e) author's inputs to the biotin-chitosan based tumour-targeting drug delivery structures. Precisely engineered biotinylated-chitosan macromolecules shaped into nanosystems are anticipated to emerge as next-generation platforms for treatment and molecular imaging modalities applications.

A Complete Review on Mucoadhesive Buccal Tablets

Drug actions can be improved by novel drug delivery system, such as mucoadhesive system. Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and prolongs the residence time of the dosage form at the site of application. Bio adhesion may be defined as the state in which two materials, at least one of which is of a biological nature, are held together for extend periods of time by interfacial forces. Buccal mucosa is the preferred site for both systemic and local drug action. The mucosa has a rich blood supply and it relatively permeable. Buccal trans mucosal delivery helps to bypass first- pass metabolism by allowing direct access to the systemic circulation through the internal jugular vein. This article briefly describes. Introduction to mucoadhesive drug delivery system, structure and function of oral mucosal membrane, buccal drug delivery and mucoadhesive property, theories and mechanism of mucoadhesion, mechanism to increase drug delivery through buccal route, buccal drug delivery system formulation design, characterization of buccal tablet, evaluation of buccal tablet.

Degradation of Titanium Sintered with Magnesium: Effect of Hydrogen Uptake

Multifunctional materials based on a combination of permanent and degradable metals open new perspectives for medical implants combining osseoconductivity and drug-delivery functions which can significantly decrease the number of implants’ revision. In this work, hybrid magnesium-titanium materials were produced via sintering, and the properties of the permanent titanium component before and after the degradation of the temporary magnesium part were evaluated. The changes of chemical composition and mechanical parameters were determined. Loading of hydrogen into the titanium part at room temperature was observed, which deteriorated the mechanical characteristics but could also simultaneously improve the biocompatibility of the permanent titanium implant. The control of degradation of the magnesium part and the modification of the titanium part are required for the development of partly degradable hybrid implants.

Selective Motion Control of a Novel Magnetic-Driven Minirobot With Targeted Drug Sustained-Release Function

In this article, we propose a novel magnetic-actuated multimodule drug sustained-release minirobot (DSM) manipulated by an external rotating electromagnetic field. The structure of the DSM is mainly divided into three parts: 1) a shell; 2) an internal propeller; and 3) a drug chamber. The shell can effectively protect the intestinal tract and reduce the various resistances during the work; the built-in propeller not only realizes active locomotion but also saves internal space, which provides the feasibility for the development of functional modules of the robot. The drug chamber pushes the carried drugs out of the chamber similar to a syringe. With structural optimization, we have realized the sustained-release and quantitative drug delivery based on the characteristics of minimagnets’ individual starting frequency- and pitch-related calculations. The main challenge to achieve these functions is to manipulate two magnets in the same magnetic field to drive different functional modules, without mutual interference between the two magnets. In this article, a series of simulations and experiments are conducted to evaluate DSM's motion performance, drug delivery function, and dose control during drug delivery. In the experiment, two different drug delivery points were set up to make DSM spray the drug on the fester areas twice respectively. Finally, an <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vitro</i> experiment using the DSM prototype was executed with fresh pig large intestine in a curved shape pipe mold.

Comparison of Long-Term Safety and Efficacy of Bioresorbable Scaffolds between Patients with and without Diabetes Mellitus.

Diabetes mellitus (DM) is a major risk of cardiovascular events. Bioresorbable stent frame materials capable of providing mechanical support and drug-delivery functions have been developed in an attempt to improve long-term outcomes. However, publications about the long-term outcomes of bioresorbable scaffolds (BRS) in DM patients are still limited. The aim of this study was to investigate the long-term safety and efficacy of BRS between patients with and without diabetes. Data regarding BRS placement in consecutive patients receiving percutaneous coronary interventions were collected from the cardiovascular center of a single tertiary medical center from 2014 to 2017. A total of 138 cases were included and followed up for 4 years. The mortality rate was 1.1% in the non-diabetic group and 4.1% in the diabetic group (p = 0.2542). No cardiac mortality was observed. One patient had an acute myocardial infarction (0.7%) in the non-diabetic group. The rate of target lesion revascularization was 3.4% in the non-diabetic group and 4.08% in the diabetic group. The ratio of target vessel revascularization was 6.74% in the non-diabetic group and 4.1% in the diabetic group. This study demonstrated no significant difference in long-term outcomes after BRS implantation between patients with and without diabetes in a single tertiary medical center.

Ultra-thin, high strength, antibiotic-eluting sutures for prevention of ophthalmic infection.

Sutures are applied almost universally at the site of trauma or surgery, making them an ideal platform to modulate the local, postoperative biological response, and improve surgical outcomes. To date, the only globally marketed drug‐eluting sutures are coated with triclosan for antibacterial application in general surgery. Loading drug directly into the suture rather than coating the surface offers the potential to provide drug delivery functionality to microsurgical sutures and achieve sustained drug delivery without increasing suture thickness. However, conventional methods for drug incorporation directly into the suture adversely affect breaking strength. Thus, there are no market offerings for drug‐eluting sutures, drug‐coated, or otherwise, in ophthalmology, where very thin sutures are required. Sutures themselves help facilitate bacterial infection, and antibiotic eye drops are commonly prescribed to prevent infection after ocular surgeries. An antibiotic‐eluting suture may prevent bacterial colonization of sutures and preclude patient compliance issues with eye drops. We report twisting of hundreds of individual drug‐loaded, electrospun nanofibers into a single, ultra‐thin, multifilament suture capable of meeting both size and strength requirements for microsurgical ocular procedures. Nanofiber‐based polycaprolactone sutures demonstrated no loss in strength with loading of 8% levofloxacin, unlike monofilament sutures which lost more than 50% strength. Moreover, nanofiber‐based sutures retained strength with loading of a broad range of drugs, provided antibiotic delivery for 30 days in rat eyes, and prevented ocular infection in a rat model of bacterial keratitis.

Potential for Treatment of Glioblastoma: New Aspects of Superparamagnetic Iron Oxide Nanoparticles.

Glioblastoma (GB) is a highly aggressive and infiltrative brain tumor characterized by poor outcomes and a high rate of recurrence despite maximal safe resection, chemotherapy, and radiation. Superparamagnetic iron oxide nanoparticles (SPIONs) are a novel tool that can be used for many applications including magnetic targeting, drug delivery, gene delivery, hyperthermia treatment, cell tracking, or multiple simultaneous functions. SPIONs are studied as a magnetic resonance imaging tumor contrast agent by targeting tumor cell proteins or tumor vasculature. Drug delivery to GB tumor has been targeted with SPIONs in murine models. In addition to targeting tumor cells for imaging or drug-delivery, SPION has also been shown to be effective at targeting for hyperthermia. Along with animal models, human trials have been conducted for a number of different modes of SPION utilization, with important findings and lessons for further preclinical and clinical experiments. SPIONs are opening up several new avenues for monitoring and treatment of GB tumors; here, we review the current research and a variety of possible clinical applications.

Chemotaxis-Driven 2D Nanosheet for Directional Drug Delivery toward the Tumor Microenvironment.

Micro/nanoscaled motor particles represent a group of intelligent materials that can precisely and rapidly respond to biological microenvironments and improve therapeutic outcomes. In order to maximize biomedical application potentials, developing a nanoscaled motor particle that is able to move autonomously toward a biological target is highly desired but still remains a critical challenge. Herein, a 2D nanosheet-based catalytic nanomotor with chemotaxis behavior is developed for enhanced drug delivery toward the tumor microenvironment. The nanomotors are constructed via a facile one-pot method and exhibit ultrathin monolayer nanosheet morphology. The 2D structure of nanomotors allows high catalytic activity, leading to responsive, sustained, and relatively long distance movement. Importantly, this nanomotor demonstrates directional motion toward the high gradient of H2 O2 fuel, exhibiting excellent chemotactic properties. After loading an anticancer drug doxorubicin, the nanomotor shows effective inhibition on cancer cell growth in simulated tumor microenvironments. The practical drug delivery application is further strengthened by the intracellular acidity-triggered biodegradability of the nanomotor after accomplishing the directional drug delivery function. This proof-of-concept work highlights the efficient catalytic activity, tumor microenvironment-guided chemotactic movement, excellent cellular performance of the 2D nanomotor, and opens an avenue for biomedical applications such as controlled and smart drug delivery.

Development of self-care textile wearables with thermally stimulated drug delivery function via biological and physical investigations

Previous studies have examined and verified the drug loading and releasing functionality from the interior channels of hollow fibers. An integrated design for self-care textile wearables with a thermally stimulated drug delivery function was proposed. To progress the in-depth development of the proposed self-care wearables, physical and biological investigations, including i) liquid release with thermal stimulation and ii) drug release upon thermal stimulation, were conducted. Physical investigation revealed that the concentration of dyes released from the heated specimens increased with higher temperature during the initial first hour of delivery. Moreover, higher cytotoxic effect could be induced with drugs delivered through heated specimens under higher thermal stimulated energy through biological examination. These results set up milestones for demonstrating the influence of thermal energy on different therapeutic requirements, such as rapid-onset transdermal medication.

Microfluidic Shear Processing Control of Biological Reduction Stimuli-Responsive Polymer Nanoparticles for Drug Delivery

We demonstrate microfluidic manufacturing of glutathione (GSH)-responsive polymer nanoparticles (PNPs) with controlled in vitro pharmacological properties for selective drug delivery. This work leverages previous fundamental work on microfluidic control of the physicochemical properties of GSH-responsive PNPs containing cleavable disulfide groups in two different locations (core and interface, DualM PNPs). In this paper, we employ a two-phase gas-liquid microfluidic reactor for the flow-directed manufacturing of paclitaxel-loaded or DiI-loaded DualM PNPs (PAX-PNPs or DiI-PNPs, where DiI is a fluorescent drug surrogate dye). We find that both PAX-PNPs and DiI-PNPs exhibit similar flow-tunable sizes, morphologies, and internal structures to those previously described for empty DualM PNPs. Fluorescent imaging of DiI-PNP formulations shows that microfluidic manufacturing greatly improves the homogeneity of drug dispersion within the PNP population compared to standard bulk microprecipitation. Encapsulation of PAX in DualM PNPs significantly increases its selectivity to cancerous cells, with various PAX-PNP formulations showing higher cytotoxicity against cancerous MCF-7 cells than against non-cancerous HaCaT cells, in contrast to free PAX, which showed similar cytotoxicity in the two cell lines. In addition, the characterization of DualM PNP formulations formed at various microfluidic flow rates reveals that critical figures of merit for drug delivery function-including encapsulation efficiencies, GSH-triggered release rates, rates of cell uptake, cytotoxicities, and selectivity to cancerous cells-exhibit microfluidic flow tunability that mirrors trends in PNP size. These results highlight the potential of two-phase microfluidic manufacturing for controlling both structure and drug delivery function of biological stimuli-responsive nanomedicines toward improved therapeutic outcomes.

Present Situation and Future Progress of Inhaled Lung Cancer Therapy: Necessity of Inhaled Formulations with Drug Delivery Functions.

Inhaled lung cancer therapy is promising because of direct and noninvasive drug delivery to the lungs with low potential for severe systemic toxicity. Thus chemotherapeutic drugs have been administered clinically by nebulization of solution or suspension formulations, which demonstrated their limited pulmonary absorption and relatively mild systemic toxicity. In all these clinical trials, however, there was no obviously superior anticancer efficacy in lung cancer patients even at the maximum doses of drugs limited by pulmonary toxicity. Therefore methods that deliver both higher anticancer efficacy and lower pulmonary toxicity are strongly desired. In addition to the worldwide availability of pressured metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) to treat local respiratory diseases, recent innovations in medicines and technologies are encouraging next steps toward effective inhaled lung cancer therapy with new therapeutic or drug delivery concepts. These include the discovery of target cells/molecules and drug candidates for novel cancer therapy, the development of high-performance inhalation devices for effective pulmonary drug delivery, and the establishment of manufacturing technologies for functional nanoparticles/microparticles. This review highlights the present situation and future progress of inhaled drugs for lung cancer therapy, including an overview of available inhalation devices, pharmacokinetics, and outcomes in clinical trials so far and some novel formulation strategies based on drug delivery systems to achieve enhanced anticancer efficacy and attenuated pulmonary toxicity.

Fabrication and in-vitro Investigation of Polycaprolactone - (Polyvinyl Alcohol/Collagen) Hybrid Nanofiber as Anti-Inflammatory Guided Tissue Regeneration Membrane.

Periodontal disease is the most common oral condition that affects the tissue surrounding the teeth. The oral cavity is colonized by an impressive array of micro-organisms, many of which can colonize the implants such as Guided Tissue Regeneration (GTR) often utilized in recovering procedures that result in inflammation interfering with the bone regeneration. In the current study, a nano-hybrid GTR membrane is developed as a heliacal structure scaffold with localized drug delivery function (Ibuprofen) as an anti-inflammatory agent. Polycaprolactone (PCL) and a blend of Polyvinyl alcohol (PVA)/collagen (Col) (50/50) were electrospun by electrospinning. Ibuprofen (Ibu) was loaded once in the PCL context and once in the hydrophilic portion (PVA/Col). The in vitro release behavior was investigated in each case. Chemical and physical properties were studied for each item. Morphology investigation indicated a heliacal structure with the total average diameter of 1266 nm consististing of porous pores with the average diameter of 256nm. The membranes indicated proper mechanical properties and appropriate biodegradation rate as a potential GTR membrane. The controlled and sustained release of Ibu was obtained from both PCL and PVA/COL loaded membranes. Kinetic model study indicated the following zero-order and Higuchi models for the optimum case of PCL loaded and PVA/Col Ibu loaded scaffolds respectively.

ZnO Nanostructures and Electrospun ZnO-Polymeric Hybrid Nanomaterials in Biomedical, Health, and Sustainability Applications.

ZnO-based nanomaterials are a subject of increasing interest within current research, because of their multifunctional properties, such as piezoelectricity, semi-conductivity, ultraviolet absorption, optical transparency, and photoluminescence, as well as their low toxicity, biodegradability, low cost, and versatility in achieving diverse shapes. Among the numerous fields of application, the use of nanostructured ZnO is increasingly widespread also in the biomedical and healthcare sectors, thanks to its antiseptic and antibacterial properties, role as a promoter in tissue regeneration, selectivity for specific cell lines, and drug delivery function, as well as its electrochemical and optical properties, which make it a good candidate for biomedical applications. Because of its growing use, understanding the toxicity of ZnO nanomaterials and their interaction with biological systems is crucial for manufacturing relevant engineering materials. In the last few years, ZnO nanostructures were also used to functionalize polymer matrices to produce hybrid composite materials with new properties. Among the numerous manufacturing methods, electrospinning is becoming a mainstream technique for the production of scaffolds and mats made of polymeric and metal-oxide nanofibers. In this review, we focus on toxicological aspects and recent developments in the use of ZnO-based nanomaterials for biomedical, healthcare, and sustainability applications, either alone or loaded inside polymeric matrices to make electrospun composite nanomaterials. Bibliographic data were compared and analyzed with the aim of giving homogeneity to the results and highlighting reference trends useful for obtaining a fresh perspective about the toxicity of ZnO nanostructures and their underlying mechanisms for the materials and engineering community.

A Facile and Universal Method to Efficiently Fabricate Diverse Protein Capsules for Multiple Potential Applications.

Proteins are considered to be one of the most important highly reproducible and monodisperse building blocks with specific functions in life sciences and material science. Protein capsules and their hybrids composed of protein-polymer conjugates have been intensively explored in drug delivery, catalysis, and cell-mimicking functions. Herein, we present a facile, universal, and efficient method to fabricate the diverse protein capsules, independent of the molecular weight (Mw), isoelectric points (IEP), wettability, amino acid sequence, and functional domains of enumerated proteins. The protein capsules were well characterized by various techniques. Furthermore, their ability to store the original protein functionality was demonstrated, which was mainly embodied in their enzyme responsiveness and good biocompatibility in vitro and in vivo. We believe that these protein capsules have multiple potential applications such as in drug delivery, tissue engineering, catalysis, and other application fields.

TCT-167 Clinical Outcomes of the Absorb Everolimus-Eluting Bioresorbable Scaffold: Final 5-Year Results From the ABSORB III Trial

The Absorb everolimus-eluting PLLA-based bioresorbable vascular scaffold (BVS) provides 1-year drug delivery and mechanical support functions similar to metallic drug-eluting stents (DES), followed by complete bioresorption in ∼3 years with recovery of vascular structure and function. The large-

Highly Biocompatible Functionalized Layer-by-Layer Ginger Lipid Nano Vectors Targeting P-selectin for Delivery of Doxorubicin to Treat Colon Cancer.

A biocompatible natural nanoparticle drug delivery system that has specific cancer-targeting function holds vast promise for cancer therapy. Here, a fucoidan/poly-lysine-functionalized layer-by-layer ginger-derived lipid vector (LbL-GDLV) was designed to target P-selectin (overexpressed by endothelial cells) and deliver a loaded drug into vascularized colon cancer. In vitro, LbL-GDLVs selectively bound to P-selectin, and the degradation of the fucoidan outer layer in a milieu similar to the cancer microenvironment resulted in rapid attachment of the cancer cell and internalization of the remaining positively charged poly-lysine coated-GDLVs. Upon enzymolysis of the poly-lysine layer inside the cancer cell, the GDLV core released loaded doxorubicin (Dox) which had the expected effects. In vivo bio-distribution studies showed that intravenously injected LbL-GDLVs exhibited enhanced accumulation at the vascularized tumor site (~ 4.4-fold higher than control vesicles), presumably due to P-selectin-mediated targeting plus the enhanced permeability and retention effect (EPR). In two animal models used to screen anti-cancer efficacy (Luc-HT-29 and HCT-116 xenografts), Dox-loaded LbL-GDLVs (LbL-GDLVs/Dox) significantly inhibited tumor growth and demonstrated much better therapeutic efficiency than free Dox. More importantly, LbL-GDLVs/Dox exhibited excellent biocompatibility, and LbL-GDLVs encapsulation largely reduced the cardiotoxicity of free Dox and avoided the notorious drug resistance of colon cells against free Dox. Together, these findings demonstrate the potential of our newly designed and highly biocompatible plant-derived LbL nanoparticles and their precise colon cancer drug delivery function.

Hybrid electrospun rapamycin-loaded small-diameter decellularized vascular grafts effectively inhibit intimal hyperplasia

For the surgical treatment of coronary artery disease, renal artery stenosis and other peripheral vascular diseases, there is significant demand for small diameter (inner diameter <6 mm) vascular grafts. However, autologous grafts are not always available when the substitute vascular grafts are severely diseased. In our previous work, hybrid small-diameter vascular grafts were successfully fabricated by combining electrospun polycaprolactone (PCL) and decellularized rat aorta (DRA). However, histological assessments of these grafts revealed the development of intimal hyperplasia, indicating potential negative impacts on the long-term patency of these grafts. To address this challenge, PCL nanofibers blended with rapamycin (RM) were electrospun outside the decellularized vascular graft to fabricate a RM-loaded hybrid tissue-engineered vascular graft (RM-HTEV), endowing the graft with a drug delivery function to prevent intimal hyperplasia. RM-HTEV possessed superior mechanical properties compared to DRA and exhibited a sustained drug release profile. To evaluate the applicability of RM-HTEV in vivo, abdominal aorta transplantation was performed on rats. Doppler sonography showed that the grafts were functional for up to 8 weeks in vivo. Moreover, histological analysis of explanted grafts 12 weeks postimplantation demonstrated that RM-HTEV significantly decreased neo-intimal hyperplasia compared with HTEV, without impairing reendothelialization and M2 macrophage polarization. Overall, RM-HTEV represents a promising strategy for developing small-diameter vascular grafts with great clinical translational potential. Statement of SignificanceIn this study, a new type of rapamycin-loaded hybrid tissue-engineered vascular graft (RM-HTEV) was fabricated using electrospinning technology. The unique hybrid bi-layer structure endowed the RM-HTEV with multi-functionality: the exterior rapamycin-loaded electrospun PCL nanofibrous layer enhanced the mechanical properties of the graft and possessed drug releasing property; the interior decellularized aorta layer with porous structure could facilitate cell proliferation and migration. In in vivo implantation experiment, RM-HTEV exhibited satisfying long-term patency rate and significantly inhibited intimal hyperplasia without impairing re-endothelialization and M2 macrophage polarization. This strategy is expected to be a promising strategy for developing bioactive small-diameter vascular grafts with great clinical translational potential.