Mitochondrial transfer in the progression and treatment of cardiac disease.

Mitochondria are the primary site for energy production and play a crucial role in supporting normal physiological functions of the human body. In cardiomyocytes (CMs), mitochondria can occupy up to 30 % of the cell volume, providing sufficient energy for CMs contraction and relaxation. However, some pathological conditions such as ischemia, hypoxia, infection, and the side effect of drugs, can cause mitochondrial dysfunction in CMs, leading to various myocardial injury-related diseases including myocardial infarction (MI), myocardial hypertrophy, and heart failure. Self-control of mitochondria quality and conversion of metabolism pathway in energy production can serve as the self-rescue measure to avoid autologous mitochondrial damage. Particularly, mitochondrial transfer from the neighboring or extraneous cells enables to mitigate mitochondrial dysfunction and restore their biological functions in CMs. Here, we described the homeostatic control strategies and related mechanisms of mitochondria in injured CMs, including autologous mitochondrial quality control, mitochondrial energy conversion, and especially the exogenetic mitochondrial donation. Additionally, this review emphasizes on the therapeutic effects and potential application of utilizing mitochondrial transfer in reducing myocardial injury. We hope that this review can provide theoretical clues for the developing of advanced therapeutics to treat cardiac diseases.

hP-MSCs attenuate severe acute pancreatitis in mice via inhibiting NLRP3 inflammasome-mediated acinar cell pyroptosis.

BACKGROUND: Severe acute pancreatitis (SAP) is a serious gastrointestinal disease that is facilitated by pancreatic acinar cell death. The protective role of human placental mesenchymal stem cells (hP-MSCs) in SAP has been demonstrated in our previous studies. However, the underlying mechanisms of this therapy remain unclear. Herein, we investigated the regularity of acinar cell pyroptosis during SAP and investigated whether the protective effect of hP-MSCs was associated with the inhibition of acinar cell pyroptosis. METHODS: A mouse model of SAP was established by the retrograde injection of sodium taurocholate (NaTC) solution in the pancreatic duct. For the hP-MSCs group, hP-MSCs were injected via the tail vein and were monitored in vivo. Transmission electron microscopy (TEM) was used to observe the pyroptosis-associated ultramorphology of acinar cells. Immunofluorescence and Western blotting were subsequently used to assess the localization and expression of pyroptosis-associated proteins in acinar cells. Systemic inflammation and local injury-associated parameters were evaluated. RESULTS: Acinar cell pyroptosis was observed during SAP, and the expression of pyroptosis-associated proteins initially increased, peaked at 24 h, and subsequently showed a decreasing trend. hP-MSCs effectively attenuated systemic inflammation and local injury in the SAP model mice. Importantly, hP-MSCs decreased the expression of pyroptosis-associated proteins and the activity of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in acinar cells. CONCLUSIONS: Our study demonstrates the regularity and important role of acinar cell pyroptosis during SAP. hP-MSCs attenuate inflammation and inhibit acinar cell pyroptosis via suppressing NLRP3 inflammasome activation, thereby exerting a protective effect against SAP.

Construction of tissue-engineered vascular grafts with enhanced patency by integrating heparin, cell-adhesive peptide, and carbon monoxide nanogenerators into acellular blood vessels.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) have garnered significant attention as a potential treatment modality for vascular bypass grafting and replacement therapy. However, the intimal hyperplasia and thrombosis are two major complications that impair graft patency during transplantation. To address this issue, we fabricated the covalent-organic framework (COF)-based carbon monoxide (CO) nanogenerator-and co-immobilized with LXW-7 peptide and heparin to establish a multifunctional surface on TEVGs constructed from acellular blood vessels for preventing thrombosis and stenosis. The cell-adhesive peptide LXW-7 could capture endothelial-forming cells (EFCs) to promote endothelialization, while the antithrombotic molecule heparin prevented thrombus formation. The reactive oxygen species (ROS)-triggered CO release suppressed the adhesion and activation of macrophages, leading to the reduction of ROS and inflammatory factors. As a result, the endothelial-to-mesenchymal transition (EndMT) triggered by inflammation was restricted, facilitating the maintenance of the homeostasis of the neo-endothelium and preventing pathological remodeling in TEVGs. When transplanted in vivo, these vascular grafts exhibited negligible intimal hyperplasia and remained patent for 3 months. This achievement provided a novel approach for constructing antithrombotic and anti-hyperplastic TEVGs.

Construction of millimeter-scale vascularized engineered myocardial tissue using a mixed gel.

Engineering myocardium has shown great clinal potential for repairing permanent myocardial injury. However, the lack of perfusing blood vessels and difficulties in preparing a thick-engineered myocardium result in its limited clinical use. We prepared a mixed gel containing fibrin (5 mg/ml) and collagen I (0.2 mg/ml) and verified that human umbilical vein endothelial cells (HUVECs) and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could form microvascular lumens and myocardial cell clusters by harnessing the low-hardness and hyperelastic characteristics of fibrin. hiPSC-CMs and HUVECs in the mixed gel formed self-organized cell clusters, which were then cultured in different media using a three-phase approach. The successfully constructed vascularized engineered myocardial tissue had a spherical structure and final diameter of 1-2 mm. The tissue exhibited autonomous beats that occurred at a frequency similar to a normal human heart rate. The internal microvascular lumen could be maintained for 6 weeks and showed good results during preliminary surface re-vascularization in vitro and vascular remodeling in vivo. In summary, we propose a simple method for constructing vascularized engineered myocardial tissue, through phased cultivation that does not rely on high-end manufacturing equipment and cutting-edge preparation techniques. The constructed tissue has potential value for clinical use after preliminary evaluation.

Promotional Properties of ACC Deaminase-Producing Bacterial Strain DY1-3 and Its Enhancement of Maize Resistance to Salt and Drought Stresses.

Salt stress and drought stress can decrease the growth and productivity of agricultural crops. Plant growth-promoting bacteria (PGPB) may protect and promote plant growth at abiotic stress. The aim of this study was to search for bacterial strains that can help crops resist rises in drought and salt stresses, to improve crop seed resistance under drought and salt stresses, and to investigate the effect of bacterial strains that can help crop resist external stresses under different stress conditions. Pseudomonas DY1-3, a strain from the soil under the glacier moss community of Tien Shan No. 1, was selected to investigate its growth-promoting effects. Previous studies have shown that this strain is capable of producing ACC (1-aminocyclopropane-1-carboxylic acid) deaminase. In this experiment, multifunctional biochemical test assays were evaluated to determine their potential as PGPB and their bacterial growth-promoting properties and stress-resistant effects on maize plants were verified through seed germination experiments and pot experiments. The results showed that strain DY1-3 has good salt and drought tolerance, as well as the ability to melt phosphorus, fix nitrogen, and produce iron carriers, IAA, EPS, and other pro-biomasses. This study on the growth-promoting effects of the DY1-3 bacterial strain on maize seeds revealed that the germination rate, primary root length, germ length, number of root meristems, and vigor index of the maize seeds were increased after soaking them in bacterial solution under no-stress, drought-stress, and salt-stress environments. In the potting experiments, seedlings in the experimental group inoculated with DY1-3 showed increased stem thicknesses, primary root length, numbers of root meristems, and plant height compared to control seedlings using sterile water. In the study on the physiological properties of the plants related to resistance to stress, the SOD, POD, CAT, and chlorophyll contents of the seedlings in the experimental group, to which the DY1-3 strain was applied, were higher than those of the control group of seedlings to which the bacterial solution was not applied. The addition of the bacterial solution reduced the content of MDA in the experimental group seedlings, which indicated that DY1-3 could positively affect the promotion of maize seedlings and seeds against abiotic stress. In this study, it was concluded that strain DY1-3 is a valuable strain for application, which can produce a variety of pro-biotic substances to promote plant growth in stress-free environments or to help plants resist abiotic stresses. In addition to this, the strain itself has good salt and drought tolerance, making it an option to help crops grown in saline soils to withstand abiotic stresses, and a promising candidate for future application in agricultural biofertilizers.

Programmed Release METTL3-14 Inhibitor Microneedle Protects Myocardial Function by Reducing Drp1 m6A Modification-Mediated Mitochondrial Fission.

M6A modification is an RNA-important processing event mediated by methyltransferases METTL3 and METTL14 and the demethylases. M6A dynamic changes after myocardial infarction (MI), involved in the massive loss of cardiomyocytes due to hypoxia, as well as the recruitment and activation of myofibroblasts. Balanced mitochondrial fusion and fission are essential to maintain intracardiac homeostasis and reduce poststress myocardial remodeling. Double-layer programmed drug release microneedle (DPDMN) breaks the limitations of existing therapeutic interventions in one period or one type of cells, and multitargeted cellular combination has more potential in MI therapy. By employing hypoxia-ischemic and TGF-ß1-induced fibrosis cell models, we found that METTL3-14 inhibition effectively decreased cardiomyocyte death through the reduction of mitochondrial fragmentation and inhibiting myofibrillar transformation. DPDMN treatment of MI in rat models showed improved cardiac function and decreased infarct size and fibrosis level, demonstrating its superior effectiveness. The DPDMN delivers METTL3 inhibitor swiftly in the early phase to rescue dying cardiomyocytes and slowly in the late phase to achieve long-term suppression of fibroblast over proliferation, collagen synthesis, and deposition. RIP assay and mechanistic investigation confirmed that METTL3 inhibition reduced the translation efficiency of Drp1 mRNA by 5'UTR m6A modification, thus decreasing the Drp1 protein level and mitochondrial fragment after hypoxic-ischemic injury. This project investigated the efficacy of DPDMNs-loaded METTL3 inhibitor in MI treatment and the downstream signaling pathway proteins, providing an experimental foundation for the translation of the utility, safety, and versatility of microneedle drug delivery for MI into clinical applications.

Bacterial Diversity Analysis and Screening for ACC Deaminase-Producing Strains in Moss-Covered Soil at Different Altitudes in Tianshan Mountains-A Case Study of Glacier No. 1.

The elevation of the snowline of the No. 1 Glacier in the Tianshan Mountains is increasing due to global warming, which has created favorable conditions for moss invasion and offers an opportunity to investigate the synergistic effects of incipient succession by mosses, plants, and soils. In this study, the concept of altitude distance was used instead of succession time. To investigate the changes of bacterial-community diversity in moss-covered soils during glacial degeneration, the relationship between bacterial community structure and environmental factors was analyzed and valuable microorganisms in moss-covered soils were explored. To do so, the determination of soil physicochemical properties, high-throughput sequencing, the screening of ACC-deaminase-producing bacteria, and the determination of ACC-deaminase activity of strains were performed on five moss-covered soils at different elevations. The results showed that the soil total potassium content, soil available phosphorus content, soil available potassium content, and soil organic-matter content of the AY3550 sample belt were significantly different compared with those of other sample belts (p < 0.05). Secondly, there was a significant difference (p < 0.05) in the ACE index or Chao1 index between the moss-covered-soil AY3550 sample-belt and the AY3750 sample-belt bacterial communities as the succession progressed. The results of PCA analysis, RDA analysis, and cluster analysis at the genus level showed that the community structure of the AY3550 sample belt and the other four sample belts differed greatly and could be divided into two successional stages. The enzyme activities of the 33 ACC-deaminase-producing bacteria isolated and purified from moss-covered soil at different altitudes ranged from 0.067 to 4.7375 U/mg, with strains DY1-3, DY1-4, and EY2-5 having the highest enzyme activities. All three strains were identified as Pseudomonas by morphology, physiology, biochemistry, and molecular biology. This study provides a basis for the changes in moss-covered soil microhabitats during glacial degradation under the synergistic effects of moss, soil, and microbial communities, as well as a theoretical basis for the excavation of valuable microorganisms under glacial moss-covered soils.

Long-Lived Photoacid-Doped Conducting Composites Induce Photocurrent for Efficient Wound Healing.

Electrical stimulation is an effective strategy for facilitating wound healing. However, it is hindered by unwieldy electrical systems. In this study, a light-powered dressing based on long-lived photoacid generator (PAG)-doped polyaniline composites is used, which can generate a photocurrent under visible light irradiation to interact with the endogenous electric field and facilitate skin growth. Light-controlled proton binding and dissociation result in oxidation and reduction of the polyaniline backbone, inducing charge transfer to generate a photocurrent. Due to the rapid intramolecular photoreaction of PAG, a long-lived proton-induced localized acidic environment is formed, which protects the wound from microbial infection. In summary, a simple and effective therapeutic strategy is introduced for light-powered and biocompatible wound dressings that show great potential for wound treatment.

Selective modes affect gene feature and function differentiation of tetraploid Brassica species in their evolution and domestication.

The genus Brassica contains a diverse group of important vegetables and oilseed crops. Genome sequencing has been completed for the six species (B. rapa, B. oleracea, B. nigra, B. carinata, B. napus, and B. juncea) in U's triangle model. The purpose of the study is to investigate whether positively and negatively selected genes (PSGs and NSGs) affect gene feature and function differentiation of Brassica tetraploids in their evolution and domestication. A total of 9,701 PSGs were found in the A, B and C subgenomes of the three tetraploids, of which, a higher number of PSGs were identified in the C subgenome as comparing to the A and B subgenomes. The PSGs of the three tetraploids had more tandem duplicated genes, higher single copy, lower multi-copy, shorter exon length and fewer exon number than the NSGs, suggesting that the selective modes affected the gene feature of Brassica tetraploids. The PSGs of all the three tetraploids enriched in a few common KEGG pathways relating to environmental adaption (such as Phenylpropanoid biosynthesis, Riboflavin metabolism, Isoflavonoid biosynthesis, Plant-pathogen interaction and Tropane, piperidine and pyridine alkaloid biosynthesis) and reproduction (Homologous recombination). Whereas, the NSGs of the three tetraploids significantly enriched in dozens of biologic processes and pathways without clear relationships with evolution. Moreover, the PSGs of B. carinata were found specifically enriched in lipid biosynthesis and metabolism which possibly contributed to the domestication of B. carinata as an oil crop. Our data suggest that selective modes affected the gene feature of Brassica tetraploids, and PSGs contributed in not only the evolution but also the domestication of Brassica tetraploids.

Prostate primary intravascular large B-cell lymphoma: A case report.

Intravascular large B-cell lymphoma (IVLBCL) is a distinct subtype of extranodal diffuse large B-cell lymphoma (DLBCL) and mainly affects elderly population characterized by selective infiltration of neoplastic cells within the lumina of small vessels. Prostate primary IVLBCL is extremely rare. Herein we present a case of a 76-year-old male patient who was admitted with symptoms of severe lower urinary tract obstruction. IVLBCL was diagnosed based on histopathological and immunohistochemical examination of the precious tissue specimens though transurethral prostate resection. Awareness and accurate diagnosis are very important to guide the clinicals in formulation of diagnosis and treatment plan.

Layer-by-Layer Assembly of a Polysaccharide "Armor" on the Cell Surface Enabling the Prophylaxis of Virus Infection.

Airborne pathogens, such as the world-spreading severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), cause global epidemics via transmission through the respiratory pathway. It is of great urgency to develop adequate interventions that can protect individuals against future pandemics. This study presents a nasal spray that forms a polysaccharide "armor" on the cell surface through the layer-by-layer self-assembly (LBL) method to minimize the risk of virus infection. The nasal spray has two separate components: chitosan and alginate. Harnessing the electrostatic interaction, inhaling the two polysaccharides alternatively enables the assembly of a barrier that reduces virus uptake into the cells. The results showed that this approach has no obvious cellular injury and endows cells with the ability to resist the infection of adenovirus and SARS-CoV-2 pseudovirus. Such a method can be a potential preventive strategy for protecting the respiratory tract against multiple viruses, especially the upcoming SARS-CoV-2 variants.

Harnessing Oxidative Microenvironment for In Vivo Synthesis of Subcellular Conductive Polymer Microesicles Enhances Nerve Reconstruction.

Conductive polymers (CPs) are promising biomaterials to address signal connection at biointerfaces for tissue regeneration. However, regulating material microstructure at the subcellular scale to provide a more seamless interface between conductive substrates and cells remains a great challenge. Here, we demonstrate that chemical factors and enzyme-carried subcellular structures at lesion site provide a natural bioreactor to self-assemble conductive microvesicles (CMVs) for improving bioelectrical signal reconstruction. The synthesized CMVs contribute to the electrical conduction of the injured nerve in the early stage. Moreover, CMVs are eventually expelled via lymphatic capillary to minimize space-occupying and chronic inflammation. Therefore, we provide a prototype to integrate specific physiological microenvironments and polymer chemistry to manufacture subcellular functional materials with self-adaptive interface in vivo for biomedical applications.

The evolution of the expansin gene family in Brassica species.

Expansin gene (EXP) family plays important roles in plant growth and crop improvement. However, it has not been well studied in the Brassica genus that includes several important agricultural and horticultural crops. To get insight to the evolution and expansion of EXP family in Brassica, Brassica EXPs which are homologues of 35 known AtEXPs of Arabidopsis were comprehensively and systematically analyzed in the present study. In total, 340 Brassica EXPs were clustered into four groups that corresponded multiple alignment to four subfamilies of AtEXPs, with divergent conserved motifs and cis-acting elements among groups. To understand the expansion of EXP family, an integrated genomic block system was constructed among Arabidopsis and Brassica species based on 24 known ancestral karyotype blocks. Obvious gene loss, segmental duplication, tandem duplication and DNA sequence repeat events were found during the expansion of Brassica EXPs, of which the segmental duplication was possibly the major driving force. The divergence time was estimated in 1109 orthologs pairs of EXPs, revealing the divergence of Brassica EXPs from AtEXPs during ~30 MYA, and the divergence of EXPs among Brassica species during 13.50-17.94 MYA. Selective mode analysis revealed that the purifying selection was the major contributor to expansion of Brassica EXPs. This study provides new insights into the evolution and expansion of the EXP family in Brassica genus.

Biofunctionalized fibrin gel co-embedded with BMSCs and VEGF for accelerating skin injury repair.

Rapid and effective repair of epithelial tissue is desirable for improving the success rate of operation and reducing postoperative complications. Hydrogel is a widely studied wound repair material, especially as a wound dressing for damaged epithelial tissue. Based on the catalytic effect of thrombin on fibrinogen, in this study, a three-dimensional fibrin gel which of adequate epithelial cell compatibility was constructed by using thrombin and fibrinogen under the cross-linking action of calcium ion. Immunofluorescence staining and hematoxylin-eosin (H&E) staining showed that bone marrow mesenchymal stem cell (BMSC) was embedded in fibrin gel. Furthermore, vascular endothelial growth factor (VEGF) was used to induce BMSC to differentiate into CD31+ and vWF+ endothelial cell (EC) in fibrin gel. The results showed that the fibrin gel surface may effectively promote the adhesion and proliferation of EC and smooth muscle cell (SMC). After 15 days of culture, it was found that the BMSC embedded in the hydrogel had differentiated into EC. The results of in vivo skin wound experiment in rats further proved that the fibrin gel containing BMSC could promote wound healing and repair, and showed the potential to promote neovascularization at the injured site. The construction method of hydrogel materials proposed in this study has potential application value in the field of regenerative medicine.

Selective endothelialization and alleviation of neointimal hyperplasia by functionalizing the Ti-O surface with l-selenocystine and KREDVC.

Due to their relatively good biocompatibility and inactivity, titanium oxide films (Ti-O) are used in the coating of coronary stents, which reduces metal corrosion, slows metal ion release, and improves endothelial cell (EC) compatibility. Here, we report further functionalizing Ti-O with biological cues for selective endothelialization. Selenocystine with an l- or a d-enantiomer was first immobilized on the Ti-O film via polydopamine to generate nitric oxide (NO) endogenously, which inhibited smooth muscle cell (SMC) proliferation, followed by the grafting of a functional KREDVC peptide to induce EC adhesion. The synergistic effects of the immobilized KREDVC, surface chirality, and NO generation on selective endothelialization were investigated. The results showed that the surface chirality of the l-enantiomer and KREDVC grafting significantly enhanced the attachment and growth of ECs compared to SMCs. An in vivo study showed von Willebrand factor expression was increased and neointimal hyperplasia was significantly decreased in samples with l-selenocystine immobilization and KREDVC grafting. In summary, these findings provide new insights on the surface modification of cardiovascular implants with selective endothelialization.

Immobilization of nano Cu-MOFs with polydopamine coating for adaptable gasotransmitter generation and copper ion delivery on cardiovascular stents.

In-stent restenosis is worsened by thrombosis, acute inflammation, and uncontrollable smooth muscle cells (SMCs) proliferation at the early stage of implantation. Tailoring the stent surface can inhibit thrombosis, intimal hyperplasia, and accelerate re-endothelialization. In situ nitric oxide (NO) generation is considered as a promising method to improve anti-coagulation and anti-hyperplasia abilities. Copper based metal organic frameworks showed great potential as catalysts for NO generation, and copper ion (Cu2+) was demonstrated to promote endothelial cells (ECs) growth. Herein, by using polydopamine as the linker and coating matrix, nanoscale copper-based metal organic frameworks (nano Cu-MOFs) were immobilized onto the titanium surface for simultaneous nitric oxide (NO) catalytic generation and Cu2+ delivery. The nano Cu-MOFs-immobilized coating exhibited desirable NO release and adaptable Cu2+ delivery. Such coating inhibited platelet aggregation and activation via NO-cGMP signaling pathway, and significantly reduced thrombosis in an ex vivo extracorporeal circulation model. NO release and Cu2+ delivery showed synergetic effect to promote EC proliferation. Moreover, SMCs and macrophage proliferation was suppressed by the nano Cu-MOFs-immobilized coating, thereby reducing neointimal hyperplasia in vivo. Overall, this biocompatible coating is convenient for the surface modification of cardiovascular stents and effectively prevents the late stent thrombosis and in-stent restenosis associated with stent implantation.

Copper-Based SURMOFs for Nitric Oxide Generation: Hemocompatibility, Vascular Cell Growth, and Tissue Response.

A coating that can generate nitric oxide (NO) for surface modification of cardiovascular stents with adaptable NO release is an efficient approach to prevent thrombosis and neointimal hyperplasia. Herein, we prepared a copper-based surface-attached metal-organic framework (Cu-SURMOFs) of copper(II) benzene-1,3,5-tricarboxylate (CuBTC) using a layer-by-layer assembly method (LBL) for NO generation on the surface of alkali-activated titanium. It was easy to control surface chemistry and NO release by changing the number of LBL deposition cycles. The obtained CuBTC coating was characterized by X-ray diffraction, scanning electron microscopy, Fourier transform infrared, and X-ray photoelectron spectroscopy analysis and was able to decompose endogenous S-nitrosoglutathoine (GSNO) to catalytically produce NO. The resulting NO flux increased with increased deposition cycles. The coating prepared with 10 cycles of deposition showed ideal NO release and promoted proliferation of endothelial cells, suppressed growth of smooth muscle cells and macrophages, and inhibited platelet adhesion and activation. Further evaluation of thrombogenicity in an arteriovenous shunt model showed that the CuBTC coating had great ability to prevent thrombosis, and in vivo implantation of CuBTC-coated titanium wire demonstrated a significant inhibition of intimal hyperplasia. The results showed that use of copper-based SURMOFs could be a promising strategy for the surface modification of cardiovascular stents.

Platelet Adhesion and Activation on Chiral Surfaces: The Influence of Protein Adsorption.

Adsorbed proteins and their conformational change on blood-contacting biomaterials will determine their final hemocompatibility. It has frequently been reported that surface chirality of biomaterials may highly influence their protein adsorption behavior. Here, lysine and tartaric acid with different chirality were immobilized onto TiO2 films respectively, and the influence of surface chirality on protein adsorption, platelet adhesion, and activation was also investigated. It showed that the l- and d-molecule grafted samples had almost the same grafting density, surface topography, chemical components, and hydrophilicity in this study. However, biological behaviors such as protein adsorption, platelet adhesion, and activation were quite different. The d-lysine grafted surface had a greater ability to inhibit both bovine serum albumin and fibrinogen adsorption, along with less degeneration of fibrinogen compared to the l-lysine anchored surface. However, the d-tartaric acid grafted surface adsorbed more protein but with less denatured fibrinogen compared to the l-tartaric acid grafted one. Further studies showed that the secondary structural change of the adsorbed albumin and fibrinogen on all surfaces with deduction of the α-helix content and increase of disordered structure, while the changing degree was apparently varied. As a result, the d-lysine immobilized surface absorbed less platelets and red blood cells and achieved slightly increased platelet activation. For tartaric acid anchored surfaces, a larger number of platelets adhered to the D-surface but were less activated compared to the L-surface. In conclusion, the surface chirality significantly influenced the adsorption and conformational change of blood plasma protein, which in turn influenced both platelet adhesion and activation.

Controlling Molecular Weight of Hyaluronic Acid Conjugated on Amine-rich Surface: Toward Better Multifunctional Biomaterials for Cardiovascular Implants.

The molecular weights (MWs) of hyaluronic acid (HA) in extracellular matrix secreted from both vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) play crucial roles in the cardiovascular physiology, as HA with appropriate MW influences important pathways of cardiovascular homeostasis, inhibits VSMC synthetic phenotype change and proliferation, inhibits platelet activation and aggregation, promotes endothelial monolayer repair and functionalization, and prevents inflammation and atherosclerosis. In this study, HA samples with gradients of MW (4 × 103, 1 × 105, and 5 × 105 Da) were prepared by covalent conjugation to a copolymerized film of polydopamine and hexamethylendiamine (PDA/HD) as multifunctional coatings (PDA/HD-HA) with potential to improve the biocompatibility of cardiovascular biomaterials. The coatings immobilized with high-MW-HA (PDA/HD-HA-2: 1 × 105 Da; PDA/HD-HA-3: 5 × 105 Da) exhibited a remarkable suppression of platelet activation/aggregation and thrombosis under 15 dyn/cm2 blood flow and simultaneously suppressed the adhesion and proliferation of VSMC and the adhesion, activation, and inflammatory cytokine release of macrophages. In particular, PDA/HD-HA-2 significantly enhanced VEC adhesion, proliferation, migration, and functional factors release, as well as the captured number of endothelial progenitor cells under dynamic condition. The in vivo results indicated that the multifunctional surface (PDA/HD-HA-2) created a favorable microenvironment of endothelial monolayer formation and functionalization for promoting reendothelialization and reducing restenosis of cardiovascular biomaterials.