Endothelial Cell Adhesion Research Articles

The Effect of Platelet Fibrin Plasma (PFP) on Postoperative Refractory Wounds: Physiologically Concentrated Platelet Plasma in Wound Repair.

Surgical wounds that can't complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing. The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function. PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate > 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells. Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds. Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.

Construction and biocompatibility evaluation of CS-FA/VA composite coating on the surface of ZE21B vascular stent

Magnesium alloys have become the focus of attention as a new generation of vascular stent materials due to their excellent mechanical properties and degradability. However, their rapid degradation rate and poor surface endothelialization performance have become key factors limiting their clinical application. In this study, the Mg-Zn-Y-Nd (ZE21B) surface was modified with the magnesium fluoride (MgF2) corrosion-resistant layer, and the polydopamine (PDA) layer was used to immobilize the chitosan (CS)-ferulic acid (FA)/vanillic acid (VA) bioactive composite coating. The results of the electrochemical and hydrogen evolution experiments showed that the corrosion current density and hydrogen release of the modified ZE21B alloy significantly decreased, and its corrosion resistance was enhanced; the results of the hemolysis rate and whole blood experiments showed that the adhesion of blood components such as white blood cells and platelets on the surface of the modified ZE21B alloy significantly decreased, improving the blood compatibility of the magnesium alloy; the results of in vitro cell experiments showed that the modified ZE21B alloy effectively promoted endothelial cell (ECs) adhesion and proliferation, and inhibited smooth muscle cell (SMCs) pathological proliferation. These enhancements suggest that the CS-FA/VA coating significantly improves both the corrosion resistance and biological compatibility of the ZE21B alloy.

Bidirectional Elastic PTFE Small Diameter Artificial Blood Vessel Grafts and Surface Antithrombotic Functionalized Construction.

Expanded polytetrafluoroethylene (ePTFE) failed to achieve clinical application in the field of small-diameter blood vessels due to its lack of elasticity in the circumferential direction and high stiffness. Excellent multidirectional elasticity and dynamic compliance matching with natural blood vessels are important means to solve the problem of acute thrombosis and poor long-term patency. Herein, novel PTFE spinning blood vessels were prepared by the PTFE emulsion electrospinning process, which not only presented good bidirectional elasticity but also promoted the adhesion and proliferation of endothelial cells and induced the contractile expression of SMCs. And, a PTFE-shish and aminated polycaprolactone (PCL)-kebab structure has been developed that converted the chemically inert PTFE surface into a drug-loading platform for the multifunctionalization of PTFE vascular grafts. It provides novel preparation methods for the application of new bidirectional elastic small-diameter artificial blood vessels and their surface functionalization construction.

Flexible and Stretchable Photoelectrochemical Sensing toward True-to-Life Monitoring of Hydrogen Peroxide Regulation in Endothelial Mechanotransduction.

Hydrogen peroxide (H2O2) levels play a vital role in redox regulation and maintaining the physiological balance of living cells, especially in cell mechanotransduction. Despite the achievements on strain-induced cellular H2O2 monitoring, the applied voltage for H2O2 electrooxidation possibly gave rise to an abnormal expression and inadequate accuracy, which was still an inescapable concern. Hence, we decorated an interlaced CuO@TiO2 nanowires (NWs) semiconductor meshwork onto a polydimethylsiloxane film-supported gold nanotubes substrate (Au NTs/PDMS) to construct a flexible photoelectrochemical (PEC) sensing platform. Under white light irradiation, CuO@TiO2 NWs synergistically exhibited great stretchability and the PEC platform enabled stable photocurrent responses from the reduction of H2O2 even during mechanical deformation. Moreover, the admirable biocompatibility and an almost negligible open circuit voltage of +0.18 V for the CuO@TiO2 NWs/Au NTs/PDMS sensor guaranteed human umbilical vein endothelial cells (HUVECs) adhesion tightly thereon even under continuous illumination for 30 min. Finally, the as-proposed stretchable PEC sensor achieved sensitive and true-to-life monitoring of transient H2O2 release during HUVECs deformation, in which H2O2 release was positively correlated to mechanical strains. This investigation opens a new shade path on in situ cellular sensing and meanwhile greatly expands the application mode of the PEC approach.

GRIP1 is Involved in the Interaction of Vimentin Filaments with Focal Adhesions in Endothelial Cells

GRIP1 is Involved in the Interaction of Vimentin Filaments with Focal Adhesions in Endothelial Cells

NIR stimulated epigallocatechin gallate loaded polydopamine with enhanced antibacterial and ROS scavenging abilities for improved infectious wound healing

Infectious wound healing is complicated with and limited by infection and oxidative stress at the wound site. In recent years, various evidences suggest that nanozymes with multiple enzymatic activities have enabled the development of novel strategies for infectious wound healing. In this study, epigallocatechin gallate loaded polydopamine (P@E) was developed to act as a potent reactive oxygen species (ROS) scavenger for scavenging ROS, alleviating inflammatory responses, and promoting infectious wound healing. Combining with near infrared (NIR) irradiation, P@E presented excellent antibacterial ability of Escherichia coli (E. coli, 93.6%) and methicillin-resistant Staphylococcus aureus (MRSA, 87.6%). Specifically, P@E+NIR exhibited the most potent antioxidant, anti-inflammatory and cell proliferation behaviors through down-regulating intracellular ROS levels (81.9% and 94.3% for NIH3T3 and RAW264.7 respectively) and inducible nitric oxide synthase (iNOS) expression level (55.7%), and up-regulating the expression levels of arginase-1 (Arg-1, 71.4%), heat shock protein 70 (HSP70, 48.6%) and platelet endothelial cell adhesion molecule (CD31, 35.3%) compared to control group. Meanwhile, it also efficiently induced M2 directional polarization of lipopolysaccharide induced murine macrophages to achieve anti-inflammation, indicated by the down-regulation of CD86 (86.2%), and up-regulation of CD206 (85.6%). Significantly, it was also observed that P@E+NIR presented the excellent behaviors of inhibiting wound infection, alleviating wound inflammation, as well as promoting skin tissue repairing. Altogether, it has developed the strategy of using P@E combining with NIR irradiation for the synergistic enhanced healing of infectious skin wound, which can serve as a promising therapeutic strategy for its clinical treatment.

Polymeric artificial heart valves derived from modified diol-based polycarbonate polyurethanes

A series of polycarbonate silicone polyurethanes (SiPCUs) have been synthesized to develop elastomers with the mechanical properties, biostability, and biocompatibility required for artificial heart valve manufacturing. In these SiPCUs, the polar functional group 4,4′-dicyclohexylmethane diisocyanate (HMDI) was incorporated into the soft segment 1,6-poly (hexamethylene carbonate) diol (PCDL) to form the modified macromolecular diol, PCDL-HMDI-PCDL. The hard segment consisted of HMDI and the chain extenders 1,4-butanediol and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyl disiloxane (BHTD). The synthesized PHC-PCUB improves the excessive microphase separation caused by the introduction of PDMS. This material possesses good physicochemical properties, long-term oxidative degradation stability, and comparatively low mechanical performance loss after degradation. Compared to the commercially available bioprosthetic heart valve (BHV) material Glut-PP, PHC-PCUB demonstrated enhanced biocompatibility, good thromboresistant properties, less calcification, and higher endothelial cell adhesion. Furthermore, valve prototypes fabricated with PHC-PCUB showed improved hemodynamic performance under various simulated conditions, highlighting the potential of PHC-PCUB as an advanced material for valve leaflets. Statement of SignificanceArtificial heart valves are crucial for treating valve diseases, and polyurethane-based valves present a promising alternative due to their durability, strong biocompatibility, and customizable properties. This study improves the biostability and post-degradation mechanical properties of siloxane polyurethanes by reducing the content of polydimethylsiloxane (PDMS) and adding modified diol (PCDL-HMDI-PCDL). By integrating hexamethylene diisocyanate (HMDI) and chain extenders, we developed polycarbonate siloxane polyurethanes (SiPCUs) that improve phase mixing, mechanical strength, and oxidative stability. These SiPCUs also exhibit good thromboresistance and calcification resistance, low cytotoxicity, and promote cell adhesion, positioning them as highly promising materials for heart valve leaflets, effectively addressing the limitations of current mechanical and bioprosthetic valves.

Glucose and pH dual-responsive hydrogels with antibacterial, reactive oxygen species scavenging, and angiogenesis properties for promoting the healing of infected diabetic foot ulcers

The healing process of diabetic foot ulcers is challenging due to the presence of a complex and severe inflammatory microenvironment, characterized by hyperglycemia, low pH, susceptibility to infection, vascular dysfunction, and over-expression of reactive oxygen species (ROS), which can potentially lead to amputation or even mortality. Herein, a glucose and pH dual-responsive hydrogel was designed and prepared by crosslinking phenylboronic acid-grafted quaternary chitosan (QF, 4 wt%) with dopamine-grafted oxidized hyaluronic acid (OD, 5 wt%) through phenylboronation, schiff-base reaction, and other techniques. The multifunctional QO/@PV@AB7 hydrogel was prepared by incorporating pravastatin-loaded chitosan nanoparticles (CSNPs@PV, 2 mg/mL) and antimicrobial peptide AMP-AB7 loaded silica nanoparticles (SiO2NPs@AB7, 0.5 mg/mL). The results demonstrate that the QO/@PV@AB7 hydrogel exhibits good responsiveness to acidic conditions and high glucose levels, while effectively scavenging various types of ROS. Moreover, it exerted protective effects against oxidative stress on cells, enhanced HUVECs viability, and promoted angiogenesis. Notably, the QO/@PV@AB7 hydrogel displayed potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Additionally, in an MRSA-infected rat model of diabetic foot wounds, administration of the QO/@PV@AB7 hydrogel led to increased secretion of pro-angiogenic factors such as vascular endothelial nitric oxide synthase (eNOS), vascular endothelial-generating factor (VEGF), and endothelial cell adhesion molecule (CD31). Furthermore, the hydrogel significantly reduced the levels of inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while simultaneously increasing the levels of anti-inflammatory cytokines such as interleukin-10 (IL-10). The findings suggest that multifunctional hydrogels incorporating PV@CSNPs and SiO2NPs@AB7 demonstrate promising potential as a therapeutic approach for the treatment of diabetic foot. Statement of SignificanceHere, a glucose and pH dual-responsive QO/@PV@AB7 hydrogel with antimicrobial and angiogenesis-promoting properties was developed for the treatment of infected wounds in diabetic feet. Our findings demonstrate that the proposed hydrogel exhibits good responsiveness, effectively scavenges various types of reactive oxygen species (DPPH, O2-, -OH, and ABTS+), provides protection against oxidative stress, enhances HUVECs cell viability, and promotes angiogenesis. Notably, it also demonstrates potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and E. coli. Additionally, in vivo experiments demonstrated that the hydrogel exhibited accelerated wound healing in MRSA-infected diabetic foot ulcers, with a reduction of four days compared to the control group.

3D-printed poly(p-dioxanone)/graphene oxide composite bioresorbable stents for congenital heart disease treatment

Bioresorbable stents (BRSs) offer significant advantages in treating congenital heart disease-related vascular stenoses, especially for pediatric patients. However, the insufficient mechanical performance of polymeric BRSs remains a critical challenge. In this study, Poly(p-dioxanone) (PPDO) was incorporated with graphene oxide (GO) for the first time to improve both mechanical properties and biocompatibility. PPDO/GO composites with varying GO contents were fabricated via solution mixing and solvent casting, and tensile tests revealed that lower GO content levels (0.2% and 0.5%) significantly improved the Young’s modulus, tensile strength, and elongation at break of PPDO due to hydrogen bonding and increased degree of crystallinity. 3D-printed PPDO/GO sliding-lock stents with optimal GO contents were fabricated by fused deposition modeling and demonstrated superior compression force compared to pristine PPDO stents. In vitro hemocompatibility and cytocompatibility assessments showed that 3D-printed PPDO/GO stents exhibited low hemolysis rate, reduced platelet adhesion, and enhanced adhesion and proliferation of endothelial cells. In vivo evaluation further demonstrated improved endothelialization in rat abdominal aortas implanted with 3D-printed PPDO/GO filaments for 4 weeks. Overall, PPDO/0.5%GO exhibited superior performance in compression force, hemocompatibility, cytocompatibility, and in vivo endothelialization. This study, for the first time, combines PPDO with GO and explains the mechanism of the enhanced mechanical properties of PPDO/GO composite material. Using 3D printing, PPDO/GO BRS with improved compression performance and biocompatibility were developed, highlighting its potential value for treating pediatric patients with CHD-related vascular stenoses.

Metabolomic signature identifies HDL and apolipoproteins as potential biomarker for systemic sclerosis with interstitial lung disease

BackgroundHigh-density lipoproteins (HDL) affect endothelial functions such as the expression of endothelial cell adhesion molecules and exert anti-apoptotic/-thrombotic functionalities. Therefore, profound analysis of lipoproteins may unveil biomarkers for (micro-)vasculopathy in systemic sclerosis (SSc) and mortality determining disease manifestations like interstitial lung disease (SSc-ILD). Because nuclear magnetic resonance (NMR) spectroscopy provides a wide range of lipoprotein parameters beyond the capabilities of classical analyses it has been used herein to examine lipoprotein profiles in SSc. MethodsTo detect the metabolic and lipidomic profile serum samples from clinically well-characterized SSc patients (n = 100) and age-and sex-matched healthy controls (n = 40) were analyzed by 1H NMR spectroscopy using Bruker's in-vitro diagnostic research (IVDr) protocol. Statistical analyses were performed to validate significant findings and to search for associations between lipoproteins and clinical phenotypes. ResultsPatients with SSc-ILD and lung fibrosis displayed reduced HDL levels. Furthermore, a reduction in apolipoprotein A1 + A2 and its HDL fractions reflected a distinct lipoprotein profile for SSc-ILD patients. This association was independent of potential clinical confounders for dyslipidemia. Notably, in SSc-ILD HDL levels correlate with FVC (forced vital capacity), DLCO (diffusion capacity of the lungs for carbon monoxide), and the modified Rodnan-Skin-Score. ConclusionThese results suggest HDL and its lipoproteins may be considered as potential new biomarkers for SSc-ILD. Immune-mediated HDL effects on the endothelium facilitate microvasculopathy - one of the pathophysiological hallmarks in SSc. Therefore, a closer prospective evaluation of the capability of HDL-determination and its lipoproteins regarding a more individualized evaluation of SSc-ILD is warranted.

NLRP3 inhibitor combined with Yimusake improves erectile dysfunction in rats with diabetes mellitus through the attenuation of pyroptosis

Erectile dysfunction (ED) is a prevalent complication associated with diabetes mellitus (DM), yet pharmacological treatments for diabetes-related erectile dysfunction (DMED) continue to be inadequate in clinical settings. Our previous studies have indicated that there is a close correlation between ED and pyroptosis, but the specific mechanism remains unclear. In this study, we sought to explore the therapeutic effects of DMED through the modulation of NLRP3, aiming to elucidate its potential molecular mechanisms. The DMED rat model was established via intraperitoneal injection of streptozotocin. The rats were randomly assigned to the control group, the DMED group, the Yimusake group, the MCC950 (NLRP3 inhibitor) group, and the MCC950+Yimusake group. Erectile function of rats was observed by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). HE staining was performed to observe the histopathological changes in penile; immunofluorescence was performed to measure the level of CD31 (Platelet endothelial cell adhesion molecule-1) in penile. Besides, immunohistochemistry, RT-qPCR and Western blot were performed to demonstrate the expression of NLRP3, caspase-1, IL-1β and eNOS. After treatment with the MCC950 and Yimusake, the number of blood sinusoids and small vessels significantly reduced in penile tissue; NLRP3, caspase-1, IL-1β proteins and mRNA expression decreased, eNOS protein and mRNA expression increased. Compare with the Y group and the MCC950 group, MCC950+Yimusake group had a more significant effect. MCC950 and Yimusake might potentially suppress pyroptosis in the penile tissue of DMED rats by modulating the NLRP3/caspase-1 pathway, thus enhancing erectile function. This discovery could offer a promising therapeutic approach for individuals with DMED.

Amorphous zinc phosphate nanoclusters loaded polycarbonate thermosensitive hydrogel: An innovative strategy for promoting wound healing

Skin trauma is a matter of great concern for public health, emphasizing the importance of reconstructing the microenvironment at the trauma site to facilitate tissue regeneration. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we prepared a thermosensitive hydrogel based on a hydrophilic-hydrophobic-hydrophilic triblock polycarbonate polymer (PTP), and created a composite hydrogel, PTPH-AZP, by incorporating amorphous zinc phosphate (AZP) nanoclusters. We evaluated the effects of PTPH-AZP on human umbilical vein endothelial cells (HUVECs) and the ability to promote skin wound healing. According to the results, PTPH-AZP was found to promote the proliferation, migration, and tube formation of HUVECs through the sustained release of Zn2+ at appropriate concentrations. In vivo experiments demonstrated that in the early-mid stages of wound healing, PTPH-AZP promotes increases in Platelet Endothelial Cell Adhesion Molecule-1 (CD31) and α-Smooth Muscle Actin (α-SMA) content within the wound area, facilitating accelerated re-epithelialization and enhanced collagen deposition. In later healing stages, epidermal thickness in the PTPH-AZP treated group was significantly improved, aligning with surrounding intact skin with no instances of attenuated or hypertrophic scarring observed. The findings from the in vivo study suggested that PTPH-AZP may have a positive impact on vascularization and wound healing. In conclusion, this study presents a promising strategy for skin wound healing, highlighting the potential of PTPH-AZP as an effective therapeutic approach.

Hydrogels with Independently Controlled Adhesion Ligand Mobility and Viscoelasticity Increase Cell Adhesion and Spreading.

A primary objective in designing hydrogels for cell culture is recreating the cell-matrix interactions found within human tissues. Identifying the most important biomaterial features for these interactions is challenging because it is difficult to independently adjust variables such as matrix stiffness, stress relaxation, the mobility of adhesion ligands and the ability of these ligands to support cellular forces. In this work we designed a hydrogel platform consisting of interpenetrating polymer networks of covalently crosslinked poly(ethylene glycol) (PEG) and self-assembled peptide amphiphiles (PA). We can tailor the storage modulus of the hydrogel by altering the concentration and composition of each network, and we can tune the stress relaxation half-life through the non-covalent bonding in the PA network. Ligand mobility can be adjusted independently of the matrix mechanical properties by attaching the RGD cell adhesion ligand to either the covalent PEG network, the dynamic PA network, or both networks at once. Interestingly, our findings show that endothelial cell adhesion formation and spreading is maximized in soft, viscoelastic gels in which RGD adhesion ligands are present on both the covalent PEG and non-covalent PA networks. The dynamic nature of cell adhesion domains, coupled with their ability to exert substantial forces on the matrix, suggests that having different presentations of RGD ligands which are either mobile or are capable of withstanding significant forces are needed mimic different aspects of complex cell-matrix adhesions. By demonstrating how different presentations of RGD ligands affect cell behavior independently of viscoelastic properties, these results contribute to the rational design of hydrogels that facilitate desired cell-matrix interactions, with the potential of improving in vitro models and regenerative therapies.

Differential effects of macrophage subtype-specific cytokines on fibroblast proliferation and endothelial cell function in co-culture system.

Macrophages are involved in several critical activities associated with tissue repair and regeneration. Current approaches in regenerative medicine are focusing on leveraging the innate immune response to accelerate tissue regeneration and improve long-term healing outcomes. Of particular interest in this regard are the currently known, four main M2 macrophage subtypes: M2interleukin (IL)-4,IL-13, M2IC, M2IL-10, M2non-selective adenosine receptor agonists (NECA) (M2IL-4,IL-13 → M2NECA). In this study, rat bone marrow-derived macrophages (M0) were polarized to each of the four subtypes M2IL-4,IL-13 → M2NECA and cultured for 72 h in vitro. Luminex assay results highlighted increased production of tissue inhibitor of metalloproteinases-1 (TIMP-1) for M2IL-4,IL-13, higher amounts of transforming growth factor-beta 1 (TGF-β1) for M2IL-10, and elevated vascular endothelial growth factor A (VEGF-A) from M2NECA. Co-culture experiments performed with M2IL-10 macrophages and L929 fibroblasts highlighted the increased production of soluble collagen within the media as well as higher amounts of collagen in the extracellular matrix. Human umbilical vein endothelial cells (HUVECs) were co-cultured with M2NECA macrophages, which demonstrated an increase in intercellular adhesion molecule (ICAM) and platelet endothelial cell adhesion molecule (PECAM), as well as increased formation of endothelial tubes. The findings of this study emphasize a critical demand for further characterization and analyses of distinct M2 subtypes and careful selection of specific macrophage populations for regeneration of specific tissue types. The current, broad classification of "M2" may be sufficient in many general tissue engineering applications, but, as conditions are constantly in flux within the microenvironment in vivo, a higher degree of specificity and control over the initial M2 subtype could result in more consistent long-term outcomes where macrophages are utilized as part of an overall regenerative strategy.

Enhanced diabetic foot ulcer treatment with a chitosan-based thermosensitive hydrogel loaded self-assembled multi-functional nanoparticles for antibacterial and angiogenic effects

Inhibiting bacterial growth and promoting angiogenesis are essential for enhancing wound healing in diabetic patients. Excessive oxidative stress at the wound site can also lead to an accumulation of reactive oxygen species. To address these challenges, a smart thermosensitive hydrogel loaded with therapeutic agents was developed. This formulation features self-assembled nanoparticles named CIZ, consisting of chlorogenic acid (CA), indocyanine green (ICG), and zinc ions (Zn2+). These nanoparticles are loaded into a chitosan-β-glycerophosphate hydrogel, named CIZ@G, which enables rapid gel formation under photothermal effects. The hydrogel demonstrates good biocompatibility and effectively releases drugs into diabetic foot ulcers (DFU) wound. Benefiting from the dual actions of CA and zinc ions, the hydrogel exhibits potent antioxidative and anti-inflammatory effects, enhances the expression of vascular endothelial growth factor (VEGF) and Platelet endothelial cell adhesion molecule-1 (CD31), and promotes angiogenesis. Both in vitro and in vivo experiments confirm that CIZ@G can effectively inhibit the growth of Staphylococcus aureus post-laser irradiation and accelerate wound remodeling within 14 days. This approach offers a new strategy for the treatment of diabetic foot ulcers (DFU), potentially transforming patient care in this challenging clinical area.

Mechanistic insights into the impact of WIN 55, 212-2, a synthetic cannabinoid, on adhesion molecules PECAM-1 and VE-cadherin in HeLa cells: implications on cancer processes

The endocannabinoid (eCB) system comprises endogenous ligands, cannabinoid receptors (CBRs), and their regulatory proteins; its alteration leads to many diseases including cancer. Thus, becomes a therapeutic target for synthetic cannabinoids aimed to control cancer cell proliferation, migration, adhesion, and invasion. However, little is known about adhesion molecules regulation through CBRs activation. The aim of this study was to evaluate the effects of a CB1/CB2 agonist, WIN-55, 212-2 (WIN), on the regulation of adhesion molecules platelet endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial cadherin (VE-cadherin) in HeLa cells. CBRs expression was evaluated by immunofluorescence staining in HeLa cells and cell viability (thiazolyl blue tetrazolium bromide), cell adhesion (crystal violet), adhesion molecules expression and location (Western blot and immunofluorescence staining assays) were all assessed on cells treated with different WIN concentrations. Receptors CB1, CB2, and G-protein-coupled receptor 55 were expressed in HeLa cells. Additionally, biphasic effects were observed in their metabolic activity and adhesive properties: low WIN concentrations resulted in significant increases whereas, high ones decreased them compared to controls (p < 0.0001), demonstrating that WIN elicits opposite effects depending on the concentration and exposure time. PECAM-1 was detected in HeLa cell’s cytoplasm, membrane, and perinuclear region, whereas VE-cadherin had a nuclear distribution. There were no significant differences in PECAM-1 and VE-cadherin expression and location, suggesting that WIN does not modulate these proteins. These findings support the potential use of WIN due to its anticancer properties without dysregulating adhesion molecules. WIN possible contribution to inhibit cancer progression should be further investigated.

Furin knockdown inhibited EndMT and abnormal proliferation and migration of endothelial cells.

In the pathogenesis of atherosclerotic cardiovascular disorders, vascular endothelium is crucial. A critical step in the development of atherosclerosis is endothelial dysfunction. Furin may play a factor in vascular remodeling, inflammatory cell infiltration, regulation of plaque stability, and atherosclerosis by affecting the adhesion and migration of endothelial cells. It is yet unknown, though, how furin contributes to endothelial dysfunction. We stimulated endothelial cells with oxidized modified lipoprotein (ox-LDL). Endothelial-to-mesenchymal transition (EndMT) was found using immunofluorescence (IF) and western blot (WB). Furin expression level and Hippo/YAP signal activation were found using reverse transcription-quantitative PCR (RT-qPCR) and WB, respectively. To achieve the goal of furin knockdown, we transfected siRNA using the RNA transmate reagent. Following furin knockdown, cell proliferation, and migration were assessed by the CCK-8, scratch assay, and transwell gold assay, respectively. WB and IF both picked up on EndMT. WB and RT-qPCR, respectively, were used to find furin's expression level. We chose the important micrornas that can regulate furin and we then confirmed them using RT-qPCR. EndMT was created by ox-LDL, evidenced by the up-regulation of mesenchymal cell markers and the down-regulation of endothelial cell markers. Furin expression levels in both protein and mRNA were increased, and the Hippo/YAP signaling pathway was turned on. Furin knockdown dramatically reduced the aberrant migration and proliferation of endothelial cells by ox-LDL stimulation. Furin knockdown can also suppress ox-LDL-induced EndMT, up-regulate indicators of endothelial cells, and down-regulate markers of mesenchymal cells. After ox-LDL stimulation and siRNA transfection, furin's expression level was up-regulated and down-regulated. Our study demonstrated that furin knockdown could affect ox-LDL-induced abnormal endothelial cell proliferation, migration, and EndMT. This implies that furin plays an important role in endothelial dysfunction.

Bio‐Inspired Design of 4D‐Printed Scaffolds Capable of Programmable Multi‐Step Transformations Toward Vascular Reconstruction

AbstractMany withered leaves or flowers spontaneously curl and transform from flattened structures into tubular constructs upon dehydration. Inspired by this phenomenon, an innovative strategy is developed to design stimuli‐responsive scaffolds that are capable of programmable transformation from flattened 2D constructs into various curled 3D tissue‐mimicking structures. Specifically, Janus‐structured scaffolds consisting of a passive layer of polycaprolactone and an active, triggered‐transforming layer of methacrylate gelatin/alginate hydrogel are 3D‐printed, which replicate the asymmetrical structure of leaves and enabled on‐demand transformation into desired curvatures and shapes through mimicking the regulation mechanism of leaves curling behavior by mesophyll matrix stiffness and vein patterns. Particularly for vascular reconstruction, multi‐step transformation scaffolds capable of primary 2D‐to‐3D transformation into tubular constructs induced by dehydration, and secondary transformation to adapt to the local intravascular geometry in vivo, are successfully developed. In addition, the oriented polycaprolactone layer of the printed scaffold can enable the adhesion, proliferation, and orientation of endothelial cells, thus demonstrating a novel strategy for the design of tissue‐engineered blood vessels. In general, this study provides an innovative design strategy for programmable biomaterials capable of shape morphing and adaptation in physiological conditions, thereby opening up a new avenue for the design of intelligent biomaterials in regenerative medicine.

Biomimetic hydrogel coatings for improving the corrosion resistance, hemocompatibility, and endothelial cell growth of the magnesium alloy

The fast biodegradation and poor biocompatibility of Mg alloys in physiological environments are still the main problems restricting their application in cardiovascular stents. In this study, the hydrogel coatings (SBMA-AAM) with different proportions of methacryloyl ethyl sulfobetaine (SBMA) and acrylamide (AAM) were built on the surface of AZ31B magnesium alloy through ultraviolet (UV) polymerization. The corrosion degradation behavior, hemocompatibility, and endothelial cell (EC) growth performance of the samples were studied in detail. The findings revealed that the uniform and dense SBMA-AAM coatings could significantly enhance the corrosion resistance. In addition, the hydrogel coatings showed excellent hydrophilicity, which increased the albumin adsorption while inhibiting the fibrinogen adsorption, and thus reduced the platelet adhesion and activation and hemolysis rate, accordingly significantly enhancing their anticoagulant performance. Furthermore, SBMA-AAM hydrogel coating promoted the EC adhesion and proliferation and the vascular endothelial growth factor (VEGF) and nitric oxide (NO) secretion of ECs, which is conducive to promoting endothelialization. When the concentration ratio of SBMA and AAM was 1: 2, the modified magnesium alloy showed the best corrosion resistance and biocompatibility. Therefore, the SBMA-AAM hydrogel coating could effectively regulate the corrosion degradation performance and biocompatibility of Mg alloys, laying a foundation for the application of Mg alloys in cardiovascular stents.

Substrates with Tunable Hydrophobicity for Optimal Cell Adhesion.

Electrospinning is a technique used to create nano/micro-fibrous materials from various polymers for biomedical uses. Polymers like polycaprolactone (PCL) are commonly used, but their hydrophobic properties can limit their applications. To enhance hydrophilicity, nonionic surfactants such as sorbitane monooleate (Span80) and poloxamer (P188) can be added to the PCL electrospinning solution without altering its net charge density. These additions enable the successful production of PCL/P188 and PCL/Span80 fibrous substrates. In this study, P188 and Span80 are incorporated into the PCL solutions; they are successfully electrospun into PCL/P188 and PCL/Span80 substrates, respectively. PCL/P188 substrates show that until a specific P188 concentration, fiber and pore sizes are similar to PCL substrates. However, exceeding 0.30% P188 concentration enlarges fibers, impacting fiber uniformity at higher concentrations. Conversely, higher concentrations of Span80 result in thicker, less uniform fibers, indicating potential disruptions in the electrospinning process. Notably, both surfactants significantly improve substrate hydrophilicity, enhancing the adhesion and proliferation of fibroblasts, endothelial cells, and smooth muscle cells. P188, in particular, shows superior efficacy in promoting cell adhesion and growth at concentrations optimized for different cell types. Therefore, precise surfactant concentrations in the electrospinning solution can lead to the optimization of electrospun substrates for tissue engineering applications.