Bioactive Metal-Organic Frameworks as a Distinctive Platform to Diagnosis and Treat Vascular Diseases.

Vascular diseases (VDs) pose the leading threat worldwide due to high morbidity and mortality. The detection of VDs is commonly dependent on individual signs, which limits the accuracy and timeliness of therapies, especially for asymptomatic patients in clinical management. Therefore, more effective early diagnosis and lesion-targeted treatments remain a pressing clinical need. Metal-organic frameworks (MOFs) are porous crystalline materials formed by the coordination of inorganic metal ions and organic ligands. Due to their unique high specific surface area, structural flexibility, and functional versatility, MOFs are recognized as highly promising candidates for diagnostic and therapeutic applications in the field of VDs. In this review, the potential of MOFs to act as biosensors, contrast agents, artificial nanozymes, and multifunctional therapeutic agents in the diagnosis and treatment of VDs from the clinical perspective, highlighting the integration between clinical methods with MOFs is generalized. At the same time, multidisciplinary cooperation from chemistry, physics, biology, and medicine to promote the substantial commercial transformation of MOFs in tackling VDs is called for.

Molecular identification and functional analysis of chitinase genes reveal their importance in the metamorphosis of Sarcophaga peregrina (Diptera: Sarcophagidae).

Chitinases play a crucial role in insect metamorphosis by facilitating chitin degradation. Sarcophaga peregrina (Robineau-Desvoidy, 1830) (Diptera: Sarcophagidae) is a typical holometabolous insect and an important hygiene pest that causes myiasis in humans and other mammals and acts as a vector for various parasitic agents, including bacteria, viruses, and parasites. Enhancing the understanding of the metamorphosis in this species has significance for vector control. In this study, we identified a total of 12 chitinase genes in S. peregrina using bioinformatic analysis methods. Based on transcriptome data, SpIDGF2 and SpCht10 were selected for further functional investigation. The down-regulation of these genes by RNA interference led to developmental delays, disruptions in molting, and differences in cuticle composition during the pupal stage. These findings underscore the pivotal role of chitinase genes in the metamorphic process and offer valuable insights for effective control strategies.

Redox stimulus disulfide conjugated polyethyleneimine as a shuttle for gene transfer.

Redox-responsive cationic polymers have gained considerable attention in gene delivery due to low cytotoxicity and spatio-temporal release of DNA into the cells. Here, we reported the synthesis of reducible disulfide conjugated polyethyleneimine (1.8 kDa) (denoted as SS-PEI) and its application to transfer pEGFP-ZNF580 plasmid (pZNF580) into EA.hy926 cell. This reducible SS-PEI polymer was prepared by one-step polycondensation reaction of low molecular weight PEI with bis-(p-nitrophenyl)-3,3'-dithiodipropionate. The SS-PEI successfully condensed pZNF580 into nano-sized complexes (170 ± 1.5 nm to 255 ± 1.6 nm) with zeta potentials of 3 ± 0.4 mV to 17 ± 0.9 mV. The complexes could be triggered to release pZNF580 when exposed to the reducing environment of 5 mM dithiothreitol. Besides, the SS-PEI exhibited low cytotoxicity. In vitro transfection results showed that SS-PEI exhibited good transfection efficiency comparable to PEI25kDa. Thus, the SS-PEI could act as an reducible gene carrier with good transfection efficiency and low cytotoxicity.

Multifunctional Gene Carriers Labeled by Perylene Diimide Derivative as Fluorescent Probe for Tracking Gene Delivery.

Multifunctional carriers with both gene transfection property and fluorescent tracking function have attracted significant attention in recent years. Herein, a kind of perylene diimide derivative (PDI-C10C8) is conjugated onto the polyethylenimine-g-poly(lactide-co-glycolide)-g-polyethylenimine (PLGA-PEI) polymer to obtain fluorescent multifunctional polymer and micelles (abbreviated as MP). Then, the REDV-G-TAT-G-NLS (TP-G) peptide sequence is grafted onto this MP to obtain multifunctional micelles labeled by perylene diimide derivative (MP-TP-G). These micelles exhibit enhanced photobleaching stability compared with the reference Cy5-labeled micelles, and the fluorescent images of cellular uptake show bright red emission without any background noise. Confocal laser scanning microscope (CLSM) experiments show that gene complexes can deliver gene into nucleus. MP-TP-G carriers do not enter into the cell nucleus, which proves that the nuclear localization signal sequence may not exert its nucleus accumulation ability via conjugating to the amphiphilic polymers. The high transfection efficiency and the enhanced photobleaching stability, combined with the ability to monitor the detailed process of cellular uptake and gene delivery, make these multifunctional micelles have great potential application for endothelialization of artificial blood vessels and gene delivery process study.

Oligohistidine and targeting peptide functionalized TAT-NLS for enhancing cellular uptake and promoting angiogenesis in vivo.

BACKGROUND: Gene therapy has been developed and used in medical treatment for many years, especially for the enhancement of endothelialization and angiogenesis. But slow endosomal escape rate is still one of the major barriers to successful gene delivery. In order to evaluate whether introducing oligohistidine (Hn) sequence into gene carriers can promote endosomal escape and gene transfection or not, we designed and synthesized Arg-Glu-Asp-Val (REDV) peptide functionalized TAT-NLS-Hn (TAT: typical cell-penetrating peptide, NLS: nuclear localization signals, Hn: oligohistidine sequence, n: 4, 8 and 12) peptides with different Hn sequence lengths. pEGFP-ZNF580 (pZNF580) was condensed by these peptides to form gene complexes, which were used to transfect human umbilical vein endothelial cells (HUVECs). RESULTS: MTT assay showed that the gene complexes exhibited low cytotoxicity for HUVECs. The results of cellular uptake and co-localization ratio demonstrated that the gene complexes prepared from TAT-NLS-Hn with long Hn sequence (n = 12) benefited for high internalization efficiency of pZNF580. In addition, the results of western blot analysis and PCR assay of REDV-TAT-NLS-H12/pZNF580 complexes showed significantly enhanced gene expression at protein and mRNA level. Wound healing assay and transwell migration assay also confirmed the improved proliferation and migration ability of the transfected HUVECs by these complexes. Furthermore, the in vitro and in vivo angiogenesis assay illustrated that these complexes could promote the tube formation ability of HUVECs. CONCLUSION: The above results indicated that the delivery efficiency of pZNF580 and its expression could be enhanced by introducing Hn sequence into gene carriers. The Hn sequence in REDV-TAT-NLS-Hn is beneficial for high gene transfection. These REDV and Hn functionalized TAT-NLS peptides are promising gene carriers in gene therapy.

Ionic Self-Assembled Derivative of Tetraphenylethylene: Synthesis, Enhanced Solid-State Emission, Liquid-Crystalline Structure, and Cu2+ Detection Ability.

A novel tetraphenylethylene complex composed of 4',4'',4''',4''''-(ethene-1,1,2,2-tetrayl)tetrabiphenyl-4-carboxylic acid (H4 ETTC) and dimethyldioctadecylammonium bromide (DOAB) with enhanced solid-state emission is designed and synthesized through an ionic self-assembly (ISA) strategy. The aggregation-induced emission property, phase behavior, and supramolecular structure of the complex are characterized by a combination of experimental measurements. The experimental results reveal that the ISA complex can self-assemble into an ordered helical supramolecular structure with enhanced luminescent properties, although the ETTC cores possess extensive conjugation and high rigidity. Due to the prolonged conjugation length, the fluorescence quantum yield of ETTC-DOAB is boosted to 66 %. Moreover, it is demonstrated that assemblies of the ISA complex are an effective sensor for Cu2+ . Owing to the disassembly modulation of ETTC-DOAB aggregations, the fluorescence emission of the assemblies can be selectively and sensitively quenched by Cu2+ , with a detection limit as low as 12.6 nm. The enhanced emission efficiency, in combination with the liquid crystallinity and superior sensing performance to Cu2+ , make the ETTC-DOAB complex a potential candidate for the fabrication of a luminescent device and chemosensor for Cu2+ detection.

Core/Shell Gene Carriers with Different Lengths of PLGA Chains to Transfect Endothelial Cells.

In order to improve the transfection efficiency and reduce the cytotoxicity of gene carriers, many strategies have been used to develop novel gene carriers. In this study, five complex micelles (MSP(2 k), MSP(4 k), MSP(6 k), MSP(8 k), and MSP(10 k)) were prepared from methoxy-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (mPEG-b-PLGA) and sorbitol-poly(d,l-lactide-co-glycolide)-graft-PEI (sorbitol-PLGA-g-PEI, where the designed molecular weights of PLGA chains were 2 kDa, 4 kDa, 6 kDa, 8 kDa, and 10 kDa, respectively) copolymers by a self-assembly method, and the mass ratio of mPEG-b-PLGA to sorbitol-PLGA-g-PEI was 1/3. These complex micelles and their gene complexes had appropriate sizes and zeta potentials, and pEGFP-ZNF580 (pDNA) could be efficiently internalized into EA.hy926 cells by their gene complexes (MSP(2 k)/pDNA, MSP(4 k)/pDNA, MSP(6 k)/pDNA, MSP(8 k)/pDNA, and MSP(10 k)/pDNA). The MTT assay results demonstrated that the gene complexes had low cytotoxicity in vitro. When the hydrophobic PLGA chain increased above 6 kDa, the gene complexes showed higher performance than that prepared from short hydrophobic chains. Moreover, the relative ZNF580 protein expression levels in MSP(6 k)/pDNA, MSP(8 k)/pDNA, and MSP(10 k)/pDNA) groups were 79.6%, 71.2%, and 73%, respectively. These gene complexes could promote the transfection of endothelial cells, while providing important information and insight for the design of new and effective gene carriers to promote the proliferation and migration of endothelial cells.

Multitargeting Gene Delivery Systems for Enhancing the Transfection of Endothelial Cells.

Gene therapy demonstrates promising prospects on cardiovascular diseases. However, nonviral gene delivery system has relatively low transfection efficiency, especially for endothelial cells (ECs). Herein, typical cell-penetrating peptide (TAT), nuclear localization signals (NLSs), and REDV functional peptide have been used to prepare multitargeting complexes. These complexes exhibit higher transfection efficiency owing to the targeting sequences of REDV and NLSs as well as the cell-penetrating function of TAT. The multifunction of the complexes provides high cell uptake, endo/lysosomal escape, and nucleus accumulation of the encapsulated DNA. Thus these multitargeting complexes can provide a potential platform for gene delivery, especially for EC transfection.

Correction: Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications.

Correction for 'Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications' by Xiangkui Ren et al., Chem. Soc. Rev., 2015, DOI: .

Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications.

Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts.

Electrospun scaffolds of silk fibroin and poly(lactide-co-glycolide) for endothelial cell growth.

Electrospun scaffolds of silk fibroin (SF) and poly(lactide-co-glycolide) (PLGA) were prepared to mimic the morphology and chemistry of the extracellular matrix. The SF/PLGA scaffolds were treated with ethanol to improve their usability. After ethanol treatment the scaffolds exhibited a smooth surface and uniform fibers. SF transformed from random coil conformation to ß-sheet structure after ethanol treatment, so that the SF/PLGA scaffolds showed low hydrophilicity and dissolving rate in water. The mechanical properties and the hydrophilicity of the blended fibrous scaffolds were affected by the weight ratio of SF and PLGA. During degradation of ethanol-treated SF/PLGA scaffolds in vitro, the fibers became thin along with the degradation time. Human umbilical vein endothelial cells (HUVECs) were seeded onto the ethanol-treated nanofibrous scaffolds for cell viability, attachment and morphogenesis studies. These SF/PLGA scaffolds could enhance the viability, spreading and attachment of HUVECs. Based on these results, these ethanol-treated scaffolds are proposed to be a good candidate for endothelial cell growth.

Amphiphilic multi-targeting copolymer micelles efficiently deliver pZNF580 to promote endothelial cell proliferation and migration.

Cationic copolymers are widely used in gene delivery as a non-viral gene vector, but their applications are limited by low transfection efficiency and high cytotoxicity. In order to enhance the transfection efficiency of copolymer micelles to endothelial cells (HUVECs) and reduce their cytotoxicity, this study synthesized an amphipathic multi-targeted copolymer micelle delivery system PCLMD-PPEGMA-NLS-TAT-REDV (TCMs). Gel test results showed that TCMs showed good pZNF580 binding ability and could effectively load the pZNF580 plasmid. The CCK-8 results show that when the concentration of TCMs is greater than 60 µg mL-1, it will affect cell viability and have low cytotoxicity. We found that the multi-targeted copolymer micelles can be effectively taken up by HUVECs in vitro. The transfection efficiency of TCMs@pZNF580 (w/wpZNF580 = 3) to HUVECs was comparable to that of the positive control group lip2000@pZNF580, and WB also showed the same trend. In addition, the TCMs@pZNF580 complex also significantly enhanced the proliferation and migration of HUVECs. The experimental results on blood vessel formation showed that TCMs@pZNF580 accelerated the vascularization of HUVECs. This experiment provided a new technology platform for targeted gene therapy, especially for endothelialization and vascularization. The research results have important reference value for the treatment of cardiovascular diseases.

Polyethylenimine-modified graphene quantum dots promote endothelial cell proliferation.

Endothelial cell proliferation plays an important role in angiogenesis and treatment of related diseases. The aim of this study was to evaluate the effect of polyethylenimine (PEI)-modified graphene quantum dots (GQDs) gene vectors on endothelial cell proliferation. The GQDs-cationic polymer gene vectors were synthesized by amidation reaction, and used to deliver pZNF580 gene to Human umbilical vein endothelial cells (HUVECs) for promoting their proliferation. The chemical modification of GQDs can adjust gene vectors' surface properties and charge distribution, thereby enhancing their interaction with gene molecules, which could effectively compress the pZNF580 gene. The CCK-8 assay showed that the cell viability was higher than 80% at higher vector concentration (40 µg/mL), demonstrating that the GQDs-cationic polymer gene vectors and their gene complex nanoparticles (NPs) having low cytotoxicity. The results of the live/dead cell double staining assay were consistent with those of the CCK-8 assay, in which the cell viability of the A-GQDs/pZNF580 (94.38 ± 6.39%), C-GQDs-PEI- polylactic acid-co-polyacetic acid (PLGA)/pZNF580 (98.65 ± 6.60%) and N-GQDs-PEI-PLGA/pZNF580 (90.08 ± 1.60%) groups was significantly higher than that of the Lipofectamine 2000/pZNF580 (71.98 ± 3.53%) positive treatment group. The results of transfection and western blot experiments showed that the vector significantly enhanced the delivery of plasmid to HUVECs and increased the expression of pZNF580 in HUVECs. In addition, the gene NPs better promote endothelial cell migration and proliferation. The cell migration rate and proliferation ability of C-GQDs-PEI-PLGA/pZNF580 and N-GQDs-PEI-PLGA/pZNF580 treatment groups were higher than those of Lipofectamine 2000/pDNA treatment group. Modified GQDs possess the potential to serve as efficient gene carriers. They tightly bind gene molecules through charge and other non-covalent interactions, significantly improving the efficiency of gene delivery and ensuring the smooth release of genes within the cell. This innovative strategy provides a powerful means to promote endothelial cell proliferation.

Peptide functionalized biomimetic gene complexes enhance specificity for vascular endothelial regeneration.

Gene delivery presents great potential in endothelium regeneration and prevention of vascular diseases, but its outcome is inevitably limited by high shear stress and instable microenvironment. Highly efficient nanosystems may alleviate the problem with strong dual-specificity for diseased site and targeted cells. Hence, biomimetic coatings incorporating EC-targeting peptides were constructed by platelets and endothelial cells (ECs) for surface modification. A series of biomimetic gene complexes were fabricated by the biomimetic coatings to deliver pcDNA3.1-VEGF165 plasmid (pVEGF) for rapid recovery of endothelium. The gene complexes possessed good biocompatibility with macrophages, stability with serum and showed no evident cytotoxicity for ECs even at very high concentrations. Furthermore, the peptide modified gene complexes achieved selective internalization in ECs and significant accumulation in endothelium-injured site, especially the REDV-modified and EC-derived gene complexes. They substantially enhanced VEGF expression at mRNA and protein levels, thereby enabling a wound to heal completely within 24 h according to wound healing assay. In an artery endothelium-injured mouse model, the REDV-modified and EC-derived gene complexes presented efficient re-endothelialization with the help of enhanced specificity. The biomimetic gene complexes offer an efficient dual-targeting strategy for rapid recovery of endothelium, and hold potential in vascular tissue regeneration.

ROS-Responsive Poly(α-l-lysine)-Based Nanoparticles Loaded with Doxycycline Combat Oxidative Stress and Bacterial Infection.

Bacterial pneumonia is one of the major threats in clinical practice, and the reactive oxygen species (ROS) generated at the infection site can exacerbate the damage. Currently, conventional antibiotic therapies have low utilization, and their excessive use can result in substantial toxicity. Nanocarrier systems provide an ideal approach for treating bacterial infection by facilitating more efficient utilization of antibiotics. In this study, the ROS-responsive amphiphilic nanoparticles (NPs) are developed and used to encapsulate the antibiotic doxycycline (DOXY) to achieve antibacterial and antioxidant functionalities. The NPs are prepared from poly(α-l-lysine) (α-PLL) and phenylboronic acid pinacol ester simultaneously conjugated carbonyldiimidazole (abbreviated as CDIPB). The phenylboronic acid ester groups on CDIPB could react with excessive ROS to suppress oxidative damage at the infection site. The ROS-responsive degradation of CDIPB also facilitates the rapid release of internal DOXY, effectively killing the accumulated bacteria. Additionally, in vitro cell experiments demonstrate the good biocompatibility of the NPs. These results suggest that the ROS-responsive amphiphilic nanoparticles can serve as a novel nanoplatform for the treatment of bacterial pneumonia.

Age determination of Chrysomya megacephala (Diptera: Calliphoridae) using lifespan patterns, gene expression, and pteridine concentration under constant and variable temperatures.

Chrysomya megacephala (Fabricius, 1794) (Diptera: Calliphoridae), is a blowfly species widely studied in medical, veterinary, and entomological research. Our study examined the impact of constant (15, 20, 25, 30, and 35 °C) and variable (ranging from 21.0 to 25.4 °C, with an average of 23.31 °C) temperatures on the development and larval body length of C. megacephala. Additionally, we analyzed the age of the adult C. megacephala through pteridine content and related metabolic genes analysis. Our findings revealed three distinct growth patterns: isomorphen diagram, isomegalen diagram, and thermal accumulated models. At constant temperatures of 15, 20, 25, 30, and 35 °C, egg-hatching times were 44.5 ± 8.9, 26.7 ± 4.6, 12.6 ± 1.1, 11.0 ± 1.0, and 9.9 ± 1.9 h, respectively, while it was 15.3 ± 5.9 h at variable temperatures. The total development times from oviposition to adult eclosion in C. megacephala required 858.1 ± 69.2, 362.3 ± 5.9, 289.6 ± 17.8, 207.3 ± 9.3, and 184.7 ± 12.1 h at constant temperatures of 15, 20, 25, 30, and 35 °C, respectively. This duration was extended to 282.0 ± 64.1 h under variable temperatures. However, no significant differences were found in hatching times and the total developmental durations between 25 °C and variable temperatures. A developmental threshold temperature (D0) of 9.90 ± 0.77 °C and a thermal summation constant (K) of 4244.0 ± 347.0° hours were ascertained. Pteridine content patterns varied significantly across constant temperatures, but not between 25 °C and variable temperatures. Sex and temperature were identified as the primary factors influencing pteridine levels in the head of C. megacephala. Gene expression associated with pteridine metabolism decreased following adult eclosion, matching with increased pteridine concentration. Further investigations are needed to explore the use of pteridine cofactors for age-grading adult necrophagous flies. These findings provide valuable insights into the lifespan of C. megacephala, thereby offering valuable groundwork for forthcoming investigations and PMImin determination.

A potential nonthrombogenic small-diameter vascular scaffold with polyurethane/poly(ethylene glycol) hybrid materials by electrospinning technique.

A small-diameter vascular graft (inner diameter 4 mm) was fabricated from polyurethane (PU) and poly(ethylene glycol) (PEG) solutions by electrospinning technology. The fiber diameter decreased from 1023 +/-185 nm to 394 +/- 106 nm with increasing weight ratio of PEG in electrospinning solutions. The PU/PEG scaffolds showed randomly nanofibrous morphology and well-interconnected porous structure. The hydrophilicity of these scaffolds was improved significantly with increasing weight ratio of PEG. The mechanical properties of electrospun PU/PEG scaffolds were obviously different from that of pure PU scaffold, which was caused by plasticizing or hardening effect imparted by PEG composition. Under hydrated state, the PU/PEG scaffolds demonstrated low mechanical performance due to the hydrophilic property of materials. Compared with dry PU/PEG scaffolds with the same weight ratio of PEG, the tensile strength and elastic modulus of hydrated PU/PEG scaffolds decreased significantly, while the elongation at break increased. The results demonstrated that the electrospun PU/PEG hybrid tubular scaffolds are potential candidates for artificial blood vessels.

Grafting of poly(ethylene glycol) monoacrylates on polycarbonateurethane by UV initiated polymerization for improving hemocompatibility.

Poly(ethylene glycol) monoacrylates (PEGMAs) with a molecular weight between 400 and 1,000 g mol(-1) were grafted by ultraviolet initiated photopolymerization on the surface of polycarbonateurethane (PCU) for increasing its hydrophilicity and improving its hemocompatibility. The surface-grafted PCU films were characterized by Fourier transformation infrared spectroscopy, X-ray photoelectron spectroscopy, water contact angle, scanning electron microscopy (SEM) and atomic force microscopy measurements. The surface properties of the modified films were studied in dry and wetted state. Blood compatibility of the surfaces was evaluated by platelet adhesion tests and adhered platelets were determined by SEM. The results showed that the hydrophilicity of the films had been increased significantly by grafting PEGMAs, and platelets adhesion onto the film surface was obviously suppressed. Furthermore, the molecular weight of PEGMAs had a great effect on the hydrophilicity and hemocompatibility of the PCU films after surface modification and increased with increasing molecular weight of PEGMAs.

Chitosan Hydrogel as Tissue Engineering Scaffolds for Vascular Regeneration Applications.

Chitosan hydrogels have a wide range of applications in tissue engineering scaffolds, mainly due to the advantages of their chemical and physical properties. This review focuses on the application of chitosan hydrogels in tissue engineering scaffolds for vascular regeneration. We have mainly introduced these following aspects: advantages and progress of chitosan hydrogels in vascular regeneration hydrogels and the modification of chitosan hydrogels to improve the application in vascular regeneration. Finally, this paper discusses the prospects of chitosan hydrogels for vascular regeneration.

Restoring endothelial function: shedding light on cardiovascular stent development.

Complete endothelialization is highly important for maintaining long-term patency and avoiding subsequent complications in implanting cardiovascular stents. It not only refers to endothelial cells (ECs) fully covering the inserted stents, but also includes the newly formed endothelium, which could exert physiological functions, such as anti-thrombosis and anti-stenosis. Clinical outcomes have indicated that endothelial dysfunction, especially the insufficiency of antithrombotic and barrier functions, is responsible for stent failure. Learning from vascular pathophysiology, endothelial dysfunction on stents is closely linked to the microenvironment of ECs. Evidence points to inflammatory responses, oxidative stress, altered hemodynamic shear stress, and impaired endothelial barrier affecting the normal growth of ECs, which are the four major causes of endothelial dysfunction. The related molecular mechanisms and efforts dedicated to improving the endothelial function are emphasized in this review. From the perspective of endothelial function, the design principles, advantages, and disadvantages behind current stents are introduced to enlighten the development of new-generation stents, aiming to offer new alternatives for restoring endothelial function.