[Silver Ion Decreases Foreign Body Reaction and Venous Neointimal Hyperplasia through the Inhibition of Interleukin-33 Expression].

INTRODUCTION: Vascular prosthetic grafts are widely used in vascular surgery; however, graft infection remains a major concern. Silver-coated vascular grafts have demonstrated anti-infection properties in clinical settings; however, whether the silver irons influence foreign body reaction or neointimal hyperplasia remains unclear. METHODS: Sodium alginate and hyaluronic acid (SA/HA) hydrogel patches loaded with rhodamine, with or without silver, were fabricated. Patches were implanted in the subcutaneous or abdominal cavity and inferior vena cava of rats. Samples were harvested on day 14 and examined via immunohistochemical and immunofluorescence analyses. RESULTS: Silver hydrogel was found to decrease the foreign body reaction; after subcutaneous and abdominal cavity implantation in rats, the capsule was found to be thinner in the silver hydrogel group than in the control hydrogel group. The silver hydrogel group had fewer CD68-positive cells and proliferating cell nuclear antigen and interleukin-33 (IL-33) dual-positive cells than the control hydrogel group. Additionally, the silver hydrogel patch reduced the neointimal thickness after patch venoplasty in rats, and the number of IL-33- and IL-1ß-positive cells was lower than that in the control patch. CONCLUSION: Silver-loaded SA/HA hydrogel patches decreased the foreign body reaction and venous neointimal hyperplasia in rats by the inhibition of IL-33 expression.

Recent advances in tissue repair of the blood-brain barrier after stroke.

The selective permeability of the blood-brain barrier (BBB) enables the necessary exchange of substances between the brain parenchyma and circulating blood and is important for the normal functioning of the central nervous system. Ischemic stroke inflicts damage upon the BBB, triggering adverse stroke outcomes such as cerebral edema, hemorrhagic transformation, and aggravated neuroinflammation. Therefore, effective repair of the damaged BBB after stroke and neovascularization that allows for the unique selective transfer of substances from the BBB after stroke is necessary and important for the recovery of brain function. This review focuses on four important therapies that have effects of BBB tissue repair after stroke in the last seven years. Most of these new therapies show increased expression of BBB tight-junction proteins, and some show beneficial results in terms of enhanced pericyte coverage at the injured vessels. This review also briefly outlines three effective classes of approaches and their mechanisms for promoting neoangiogenesis following a stroke.

A hyaluronic acid / chitosan composite functionalized hydrogel based on enzyme-catalyzed and Schiff base reaction for promoting wound healing.

The healing of full-thickness skin defect has been a clinical challenge. Hydrogels with multiple functions inspired by extracellular matrix are expected to be used as wound dressing. In this paper, dopamine-grafted oxidized hyaluronic acid was blended with quaternary ammonium chitosan to form a composite functionalized hydrogel by enzyme-catalyzed cross-linking and Schiff base reaction. The hydrogel has convenient preparation, good biocompatibility, antibacterial and antioxidant, high adhesion and self-healing properties. The results in vivo show that the hydrogel can effectively close the wound and accelerate the speed of wound healing by up-regulating the expression of angiogenic protein and promoting the distribution of collagen deposition more uniform and regular. It is expected that this composite functionalized hydrogel dressing has great potential in wound regeneration.

New insights into balancing wound healing and scarless skin repair.

Scars caused by skin injuries after burns, wounds, abrasions and operations have serious physical and psychological effects on patients. In recent years, the research of scar free wound repair has been greatly expanded. However, understanding the complex mechanisms of wound healing, in which various cells, cytokines and mechanical force interact, is critical to developing a treatment that can achieve scarless wound healing. Therefore, this paper reviews the types of wounds, the mechanism of scar formation in the healing process, and the current research progress on the dual consideration of wound healing and scar prevention, and some strategies for the treatment of scar free wound repair.

Three-dimensional bioprinting of artificial blood vessel: Process, bioinks, and challenges.

The coronary artery bypass grafting is a main treatment for restoring the blood supply to the ischemic site by bypassing the narrow part, thereby improving the heart function of the patients. Autologous blood vessels are preferred in coronary artery bypass grafting, but their availability is often limited by due to the underlying disease. Thus, tissue-engineered vascular grafts that are devoid of thrombosis and have mechanical properties comparable to those of natural vessels are urgently required for clinical applications. Most of the commercially available artificial implants are made from polymers, which are prone to thrombosis and restenosis. The biomimetic artificial blood vessel containing vascular tissue cells is the most ideal implant material. Due to its precision control ability, three-dimensional (3D) bioprinting is a promising method to prepare biomimetic system. In the 3D bioprinting process, the bioink is at the core state for building the topological structure and keeping the cell viable. Therefore, in this review, the basic properties and viable materials of the bioink are discussed, and the research of natural polymers in bioink, including decellularized extracellular matrix, hyaluronic acid, and collagen, is emphasized. Besides, the advantages of alginate and Pluronic F127, which are the mainstream sacrificial material during the preparation of artificial vascular graft, are also reviewed. Finally, an overview of the applications in the field of artificial blood vessel is also presented.

Deoxygenative Radical Boration of Inert Amides via a Combination of Relay and Cooperative Catalysis.

Invited for the cover of this issue is the group of Prof. Xiaoming Wang at the Shanghai Institute of Organic Chemistry and Hangzhou Institute for Advanced Study, University of the Chinese Academy of Sciences. The image depicts a combination of relay and cooperative catalysis with a triple iridium-photoredox-organocatalysis system to achieve an unprecedented reductive boration of amides. Read the full text of the article at 10.1002/chem.202301199.

Deoxygenative Radical Boration of Inert Amides via a Combination of Relay and Cooperative Catalysis.

One of the most challenging tasks in organic synthesis is to develop novel methodologies for rapid construction of complex molecules starting from easily available yet inert raw materials. In this context, multi-catalysis strategies have attracted great attention in the discovery of new reactivity profiles that may allow access to many difficult or unattainable transformations. So far the deoxygenative functionalization of ubiquitous amides is usually achieved by nucleophilic attack on the imine or iminium ion intermediate formed via activation of the C=O bond, and these functionalization reagents were often confined to C-based nucleophiles, which largely limited the diversity of the resultant amines. Herein, we disclose a combined strategy of relay and cooperative catalysis with a triple iridium-photoredox-organocatalysis system to achieve an unprecedented reductive boration of amides, affording valuable α-amino boron products which are viable building blocks. In this transformation, the Ir-catalyzed semi-reduction of amides is successfully incorporated with photo-organic catalyzed nucleophilic boryl radical addition, thus delivering the corresponding α-boryl amines in high efficiency.

Surface modification of biodegradable magnesium alloy with poly (L-lactic acid) and sulfonated hyaluronic acid nanoparticles for cardiovascular application.

Magnesium (Mg) and its alloys have attracted extensive attention of researchers in the field of cardiovascular implants due to their good mechanical properties and biosafety. Constructing a multifunctional hybrid coating seems to be an effective strategy to address the insufficient endothelialization and poor corrosion resistance of Mg alloy vascular stents. In this study, a dense layer of magnesium fluoride (MgF2) was prepared on the surface of Mg alloy aiming at better corrosion resistance; Thereafter, sulfonated hyaluronic acid (S-HA) was made into small sized nanoparticles (NP) which were deposited on the MgF2 surface by self-assembly method, followed with poly-L-lactic acid (PLLA) coating preparation by one-step pulling method. The blood and cell tests showed that the composite coating had good blood compatibility, pro-endothelial, anti-hyperplasia and anti-inflammatory functions. Compared to current clinical PLLA@ Rapamycin coating, our PLLA/NP@S-HA coating showed better functions of promoting endothelial cells growth. These results strongly furnished a promising and feasible strategy for the surface modification of Mg-based degradable cardiovascular stents.

Application of Hydrogels as Three-Dimensional Bioprinting Ink for Tissue Engineering.

The use of three-dimensional bioprinting technology combined with the principle of tissue engineering is important for the construction of tissue or organ regeneration microenvironments. As a three-dimensional bioprinting ink, hydrogels need to be highly printable and provide a stiff and cell-friendly microenvironment. At present, hydrogels are used as bioprinting inks in tissue engineering. However, there is still a lack of summary of the latest 3D printing technology and the properties of hydrogel materials. In this paper, the materials commonly used as hydrogel bioinks; the advanced technologies including inkjet bioprinting, extrusion bioprinting, laser-assisted bioprinting, stereolithography bioprinting, suspension bioprinting, and digital 3D bioprinting technologies; printing characterization including printability and fidelity; biological properties, and the application fields of bioprinting hydrogels in bone tissue engineering, skin tissue engineering, cardiovascular tissue engineering are reviewed, and the current problems and future directions are prospected.

Functional liquid-infused PDMS sponge-based catheter with antithrombosis, antibacteria, and anti-inflammatory properties.

A functional liquid-infused catheter surface strategy has recently attracted increasing attention for blood transport with the remarkable antibiofouling performance. Nevertheless, constructing porous structure inside a catheter with effective functional liquid-locking ability remains extremely challenging. Herein, the central cylinder mold and sodium chloride particle templates technique was used to create a PDMS sponge-based catheter that stores a stable functional liquid. Our multifunctional liquid-infused PDMS sponge-based catheter can not only exhibit bacterial resistant, less macrophages infiltration, a slighter inflammation response, but also capability to prevent platelet adhesion and activation, and impressively reduce thrombosis in vivo even at high shear. Therefore, these desirable properties will endow the prospective practical applications and serve as a watershed moment in the development of biomedical devices.

The enhanced antibacterial effect of BNNS_Van@CS/MAO coating on Mg alloy for orthopedic applications.

The development of multifunctional Mg-based active implants with controllable degradation and antibacterial capabilities has become a hotspot in the research field of biodegradable metallic materials. To this end, a BN nanosheets (BNNS) _vancomycin (Van) @chitosan (CS) nanocomposite coating containing two antibacterial components (BNNS and Van) was prepared on Mg alloys via a micro-arc oxidation (MAO) pre-treatment combined with following electrodeposition. The related characterizations of the coating show that the composite coating has a high roughness, hydrophobicity and fair corrosion resistance. In vitro antibacterial experiments show that the BNNS_Van@CS/MAO composite coating have obvious inhibitory effect on the growth of both E. coli and S. aureus. The antibacterial effect of the BNNS_Van@CS/MAO composite coating was attributed to the synergistic effect of CS, BNNS and Van. This study provides a valuable surface modification strategy for developing multifunctional Mg-based implants with good corrosion resistance and antibacterial properties.

Response of cardiovascular environment to sulfonated hyaluronic acid with higher sulfur content.

Sulfonated hyaluronic acid (S-HA) has been shown to promote endothelialization in the treatment of cardiovascular diseases according to amounts of investigations. In this study, two kinds of S-HA with higher sulfur content were obtained successfully. Through a series of cell experiments, it was found that the S-HA with higher sulfur content not only possessed stronger ability of promoting the growth and migration of endothelial cells, regulating the phenotype of smooth muscle cells, but also had stronger anti-inflammatory function. Furthermore, all the S-HA molecules are very compatible with blood.

Preparation of Fluorescent Carbon Dots Composites and Their Potential Applications in Biomedicine and Drug Delivery-A Review.

Carbon dots (CDs), a new member of carbon nanostructures, rely on surface modification and functionalization for their good fluorescence phosphorescence and excellent physical and chemical properties, including small size (<10 nm), high chemical stability, biocompatibility, non-toxicity, low cost, and easy synthesis. In the field of medical research on cancer (IARC), CDs, a new material with unique optical properties as a photosensitizer, are being applied to heating local apoptosis induction of cancer cells. In addition, imaging tools can also be combined with a drug to form the nanometer complex compound, the imaging guidance for multi-function dosage, so as to improve the efficiency of drug delivery, which also plays a big role in genetic diagnosis. This paper mainly includes three parts: The first part briefly introduces the synthesis and preparation of carbon dots, and summarizes the advantages and disadvantages of different preparation methods; The second part introduces the preparation methods of carbon dot composites. Finally, the application status of carbon dot composites in biomedicine, cancer theranostics, drug delivery, electrochemistry, and photocatalysis is summarized.

Wood-Derived Vascular Patches Loaded With Rapamycin Inhibit Neointimal Hyperplasia.

Background: Patches are commonly used to close blood vessels after vascular surgery. Most currently used materials are either prosthetics or animal-derived; although natural materials, such as a leaf, can be used as a patch, healing of these natural materials is not optimal; rhodamine and rapamycin have been used to show that coating patches with drugs allow drug delivery to inhibit neointimal hyperplasia that may improve patch healing. Wood is abundant, and its stiffness can be reduced with processing; however, whether wood can be used as a vascular patch is not established. We hypothesized that wood can be used as a vascular patch and thus may serve as a novel plant-based biocompatible material. Method: Male Sprague-Dawley rats (aged 6-8 weeks) were used as an inferior vena cava (IVC) patch venoplasty model. After softening, wood patches coated with rhodamine and rapamycin were implanted into the rat subcutaneous tissue, the abdominal cavity, or the IVC. Samples were explanted on day 14 for analysis. Result: Wood patches became soft after processing. Patches showed biocompatibility after implantation into the subcutaneous tissue or the abdominal cavity. After implantation into the IVC, the patches retained mechanical strength. There was a significantly thinner neointima in wood patches coated with rapamycin than control patches (146.7 ± 15.32 µm vs. 524.7 ± 26.81 µm; p = 0.0001). There were CD34 and nestin-positive cells throughout the patch, and neointimal endothelial cells were Eph-B4 and COUP-TFII-positive. There was a significantly smaller number of PCNA and α-actin dual-positive cells in the neointima (p = 0.0003), peri-patch area (p = 0.0198), and adventitia (p = 0.0004) in wood patches coated with rapamycin than control patches. Piezo1 was expressed in the neointima and peri-patch area, and there were decreased CD68 and piezo1 dual-positive cells in wood patches coated with rapamycin compared to control patches. Conclusion: Wood can be used as a novel biomaterial that can be implanted as a vascular patch and also serve as a scaffold for drug delivery. Plant-derived materials may be an alternative to prosthetics or animal-based materials in vascular applications.

Advances in Hyaluronic Acid for Biomedical Applications.

Hyaluronic acid (HA) is a large non-sulfated glycosaminoglycan that is the main component of the extracellular matrix (ECM). Because of its strong and diversified functions applied in broad fields, HA has been widely studied and reported previously. The molecular properties of HA and its derivatives, including a wide range of molecular weights but distinct effects on cells, moisture retention and anti-aging, and CD44 targeting, promised its role as a popular participant in tissue engineering, wound healing, cancer treatment, ophthalmology, and cosmetics. In recent years, HA and its derivatives have played an increasingly important role in the aforementioned biomedical fields in the formulation of coatings, nanoparticles, and hydrogels. This article highlights recent efforts in converting HA to smart formulation, such as multifunctional coatings, targeted nanoparticles, or injectable hydrogels, which are used in advanced biomedical application.

Delivery of rivaroxaban and chitosan rapamycin microparticle with dual antithrombosis and antiproliferation functions inhibits venous neointimal hyperplasia.

Neointimal hyperplasia is a complex process after vascular interventions, acute platelet deposition and smooth muscle cell proliferation both contributed to this process. There are still no perfect solutions to solve this problem. Rivaroxaban is a novel anticoagulant that has been widely used in clinic, it has a good pharmacological effects both in vivo and in vitro. Chitosan microparticle rapamycin (MP-rapa) was fabricated, interspaces of polyglycolic acid (PGA) scaffold were used as a reservoir of MP-rapa, and the scaffold was coated with hyaluronic acid rivaroxaban (MP-rapa-riva). Scanning electronic microscopy (SEM) photographs were taken and water contact angles were measured, rat inferior vena cava (IVC) patch venoplasty model was used; patches were harvested at day 14 and examined by immunohistochemistry and immunofluorescence. SEM photographs showed the microparticles rapamycin were inside the interspace of the scaffold, hyaluronic acid rivaroxaban was also successfully coated onto the surface of the scaffold. There was a thinner neointima, fewer proliferating cell nuclear antigen (PCNA) positive cells, fewer macrophages in the MP-rapa and MP-rapa-riva grafts compared to the control PGA graft. The result showed that this scaffold with dual anticoagulation and antiproliferation functions can effectively inhibit venous neointimal hyperplasia, although this is an animal experiment, it showed promising potential clinical application in the future.

Injectable gelatin/oxidized dextran hydrogel loaded with apocynin for skin tissue regeneration.

Acute skin injury should be treated in time, due to many factors will affect the normal healing process of wounds, hinder tissue regeneration, and eventually form chronic wounds. Herein, an injectable, in-situ gel-forming hydrogel has been fabricated. The hydrogel is stabilized by dynamic Schiff base and composed of gelatin (Gel), oxidized dextran (Odex) and apocynin (Apo). In vitro studies have shown that this hydrogel has good injectability, plasticity, self-healing and efficient hemostatic properties. The hydrogel has good cytocompatibility with HaCaT and L929 cells by the Live/Dead cell staining. Furthermore, in vivo studies have shown that hydrogel loaded with APO can accelerate angiogenesis and skin tissue regeneration by reducing wound inflammation. Therefore, the injectable Gel/Odex/Apo hydrogel has the advantages of simple preparation process, convenient use and multifunction, etc., it is a promising wound dressing for full-thickness skin repair and has great potential in the field of skin tissue regeneration.

Injectable multifunctional CMC/HA-DA hydrogel for repairing skin injury.

Injectable Hydrogels with adhesive, antioxidant and hemostatic properties are highly desired for promoting skin injury repair. In this study, we prepared a multi-functional carboxymethyl chitosan/hyaluronic acid-dopamine (CMC/HA-DA) hydrogel, which can be crosslinked by horseradish peroxidase and hydrogen peroxide. The antioxidation, gelation time, degradability, rheology and antihemorrhagic properties of hydrogels can be finely tuned by varying composition ratio. The cytocompatibility test and hemolysis test confirmed that the designed hydrogel holds good biocompatibility. More importantly, the repair effect of the hydrogel on full-thickness skin injury model in mice was studied. The results of wound healing, collagen deposition, immunohistochemistry and immunofluorescence showed that CMC/HA-DA hydrogel could significantly promote angiogenesis and cell proliferation at the injured site. Notably, the inflammatory response can also be regulated to promote the repair of full-thickness skin defect in mice. Results indicate that this injectable CMC/HA-DA hydrogel holds high application prospect for promising wound healing.

Tailoring ZE21B Alloy with Nature-Inspired Extracellular Matrix Secreted by Micro-Patterned Smooth Muscle Cells and Endothelial Cells to Promote Surface Biocompatibility.

Delayed surface endothelialization is a bottleneck that restricts the further application of cardiovascular stents. It has been reported that the nature-inspired extracellular matrix (ECM) secreted by the hyaluronic acid (HA) micro-patterned smooth muscle cells (SMC) and endothelial cells (EC) can significantly promote surface endothelialization. However, this ECM coating obtained by decellularized method (dECM) is difficult to obtain directly on the surface of degradable magnesium (Mg) alloy. In this study, the method of obtaining bionic dECM by micro-patterning SMC/EC was further improved, and the nature-inspired ECM was prepared onto the Mg-Zn-Y-Nd (ZE21B) alloy surface by self-assembly. The results showed that the ECM coating not only improved surface endothelialization of ZE21B alloy, but also presented better blood compatibility, anti-hyperplasia, and anti-inflammation functions. The innovation and significance of the study is to overcome the disadvantage of traditional dECM coating and further expand the application of dECM coating to the surface of degradable materials and materials with different shapes.

PLGA Nanoparticle Rapamycin- or Necrostatin-1-Coated Sutures Inhibit Inflammatory Reactions after Arterial Closure in Rats.

Background: The inflammatory reaction of sutures and oozing after arterial closure depends on the suture material and the amount of oozing surrounding the sutures. Anti-inflammation coatings have been proven to be an effective strategy to decrease this reaction. The aim of this study was to establish an arterial closure oozing model in rats and to test the effect of poly (lactic-co-glycolic acid) (PLGA) nanoparticle (NP) rapamycin- or necrostatin-1(NEC-1)-coated sutures on the inflammatory reaction after arterial closure. Methods and Materials: A 10 mm arteriotomy was carried out on the carotid artery of Sprague-Dawley rats and closed using 11-0 sutures. PLGA NP-rapamycin and NEC-1 were made. The 11/0 nylon sutures were coated with PLGA NP-rapamycin and NEC-1. Sutures were examined by scanning electron microscopy, hemolysis test, and cumulative release. The carotid arteriotomy was closed using uncoated PLGA NP-rapamycin- and NP-NEC-1-coated sutures. The carotid artery was harvested on day 7. Tissues were examined by histology and immunohistochemistry. Results: There were severe inflammatory reactions in the oozing arteries compared to the normal healing arteries (P = 0.0192). PLGA NP-rapamycin- and NEC -1-coated sutures reduced foreign body reaction compared to the uncoated sutures. There were significantly smaller number of CD3 (P = 0.0068), CD45 (P = 0.0300), and CD68 (P = 0.0011) cells in the PLGA NP-rapamycin- and NP-NEC-1-coated groups compared to the uncoated group. There was a smaller number of p-mTOR (P = 0.0198)-positive cells in the PLGA NP-rapamycin-coated group compared to the uncoated group. There was a smaller number of TNFα (P = 0.0198)-positive cells in the PLGA NP-NEC-1-coated group compared to the uncoated group. Conclusions: In this rat carotid artery oozing model, PLGA NP-rapamycin- or NP-NEC-1-coated sutures can inhibit inflammatory reaction and foreign body reaction. Although this was a small rodent animal experiment, this coated suture may have a potential clinical application in the future.