Release of exosomes from injectable silk fibroin and alginate composite hydrogel for treatment of myocardial infarction.

Myocardial infarction (MI) is considered as a significant cause of death globally. Exosomes (EXOs) are essential for intercellular communication and pathophysiology of several cardiovascular diseases. Nevertheless, the short half-life and rapid clearance of EXOs leads to a lack of therapeutic doses delivered to the lesioned area. Therefore, an injectable silk fibroin and alginate (SF/Alg) composite hydrogel was developed to bind folate receptor-targeted EXOs (FA-EXOs) derived from H9C2 cells for the therapy of myocardial injury following myocardial infarction-ischemia/reperfusion (MI-I/R). The resulting composite exhibits a variety of properties, including adjustable gelation kinetics, shear-thinning injectability, soft and dynamic stability that adapts to the heartbeat, and outstanding cytocompatibility. After injected into the damaged rat heart, administration of SF/Alg + FA-EXOs significantly enhanced cardiac function as demonstrated by improved ejection fraction, fractional shortening and decreased fibrosis area. The results of real-time PCR and immunofluorescence staining show a remarkable up-regulation in the expression of proteins (CD31) and genes (VWF and Serca2a) related to the heart. Conversely, expression of fibrosis-related genes (TGF-ß1) decreased significantly. Therefore, the obtained SF/Alg + FA-EXOs system remarkably enhanced the intercellular interactions, promoted cell proliferation and angiogenesis, and achieved an outstanding therapeutic effect on MI.

Silk fibroin and hydroxypropyl cellulose composite injectable hydrogel-containing extracellular vesicles for myocardial infarction repair.

Extracellular vesicles (EVs) have been recognized as one of the promising specific drugs for myocardial infarction (MI) prognosis. Nevertheless, low intramyocardial retention of EVs remains a major impediment to their clinical application. In this study, we developed a silk fibroin/hydroxypropyl cellulose (SF/HPC) composite hydrogel combined with AC16 cell-derived EVs targeted modification by folic acid for the treatment of acute myocardial infarction repair. EVs were functionalized by distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) via noncovalent interaction for targeting and accelerating myocardial infarction repair.In vitro, cytocompatibility analyses revealed that the as-prepared hydrogels had excellent cell viability by MTT assay and the functionalized EVs had higher cell migration by scratch assay.In vivo, the composite hydrogels can promote myocardial tissue repair effects by delaying the process of myocardial fibrosis and promoting angiogenesis of infarct area in MI rat model.

Integration of metformin-loaded MIL-100(Fe) into hydrogel microneedles for prolonged regulation of blood glucose levels.

The transdermal drug delivery based on microneedles (MNs) provides a suitable and painless self-administration for diabetic patients. In this work, the hydrogel-forming MNs were firstly fabricated using poly(vinyl alcohol) (PVA) and chitosan (CS) as matrix. A hypoglycemic drug, metformin (Met), had been loaded into MIL-100(Fe). Then, both of free Met and Met-loaded MIL-100(Fe) were integrated into hydrogel-forming MNs for regulation of blood glucose levels (BGLs) on diabetic rats. After penetrated into the skin, the free Met could be firstly released from MNs. Due to the absorption of interstitial fluid and subsequent release of loaded Met from MIL-100(Fe), leading to a sustainable and long-term drug release behaviors. A notable hypoglycemic effect and low risk of hypoglycemia could be obtained on diabetic rat modelsin vivo. The as-fabricated hydrogel-forming MNs expected to become a new type of transdermal drug delivery platform for transdermal delivery of high-dose drugs to form a long-term hypoglycemic effect.

Microbiome in a ground-based analog cabin of China Space Station during a 50-day human occupation.

Dead-corner areas in space station that untouched by the clean-up campaign often experience microorganisms outbreaks, but the microbiome of these areas has never been studied. In this study, the microbiome in a ground-based analog ``Tianhe'' core module of China Space Station was first investigated during a 50-day three-crew occupation. Dead-corner areas were receiving attention by adopting a new sampling method. Results indicate that the astronauts occupation did not affect the dominant bacteria community, but affected a small proportion. Due to the frequent activity of astronauts in the work and sleep areas, the biomarkers in these two areas are common human skin surface and gut microorganisms, respectively. For areas that astronaut rarely visits, the biomarkers in which are common environmental microbial groups. Fluorescence counting showed that 70.12-84.78% of bacteria were alive, with a quantity of 104-105 cells/100 cm2. With the occupation time extension, the number of microorganisms increased. At the same sampling time, there was no significant bioburden difference in various locations. The cultivable bioburden ranged from 101 to 104 colony forming unit (CFU)/100 cm2, which are the following eight genera Penicillium, Microsphaeropsis, Stachybotrys, Humicola, Cladosporium, Bacillus, Planomicrobium, and Acinetobacter. Chryseomicrobium genus may be a key focus for future microbial prevention and control work.

Rizatriptan benzoate-loaded dissolving microneedle patch for management of acute migraine therapy.

In this study, dissolving microneedles (MNs) using polyvinyl alcohol (PVA) and poly (1-vinylpyrrolidone-co-vinyl acetate) (P(VP-co-VA)) as matrix materials were developed for transdermal delivery of rizatriptan benzoate (RB) for acute migraine treatment. In-vitro permeation studies were conducted to assess the feasibility of the as-fabricated dissolving MNs to release RB. Drug skin penetration were tested by Franz diffusion cells, showing an increase of the transdermal flux compared to passive diffusion due to the as-fabricated dissolving MNs having a sufficient mechanical strength to penetrate the skin and form microchannels. The pharmacological study in vivo showed that RB-loaded dissolving MNs significantly alleviated migraine-related response by up-regulating the level of 5-hydroxytryptamine (5-HT) and down-regulating the levels of calcitonin gene-related peptide (CGRP) and substance P (SP). In conclusion, the RB-loaded dissolving MNs have advantages of safety, convenience, and high efficacy over conventional administrations, laying a foundation for the transdermal drug delivery system treatment for acute migraine.

Facile preparation of self-healing hydrogels based on chitosan and PVA with the incorporation of curcumin-loaded micelles for wound dressings.

The increased demand for improved strategies for wound healing has, in recent years, motivated the development of multifunctional hydrogels with favorable bio-compatibility and antibacterial properties. To this regard, the current study presented the design of a novel self-healing composite hydrogel that could perform as wound dressing for the promotion of wound healing. The composite hydrogels were composed of polyvinyl alcohol (PVA), borax and chitosan functionalized with sialic acid (SA-CS) and curcumin loaded pluronic F127 micelles. The hydrogels were formed through the boronic ester bond formation between PVA, SA-CS and borax under physiological conditions and demonstrated adjustable mechanical properties, gelation kinetics and antibacterial properties. When incubating with NIH3T3 cells, the hydrogels also demonstrated good biocompatibility. These aspects offer a promising foundation for their prospective applications in developing clinical materials for wound healing.

Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia.

There is an urgent need for research into effective interventions for pain management to improve patients' life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs' tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.

Red blood cell membrane-coated functionalized Cu-doped metal organic framework nanoformulations as a biomimetic platform for improved chemo-/chemodynamic/photothermal synergistic therapy.

Nanoformulations for combining chemotherapy, chemodynamic therapy, and photothermal therapy have enormous potential in tumor treatment. Coating nanoformulations with cell membranes endows them with homologous cellular mimicry, enabling nanoformulations to acquire new functions and properties, including homologous targeting and long circulation in vivo, and can enhance internalization by homologous cancer cells. Herein, we fused multifunctional biomimetic nanoformulations based on Cu-doped zeolitic imidazolate framework-8 (ZIF-8). Hydroxycamptothecin (HCPT), a clinical anti-tumor drug, was encapsulated into ZIF-8, which was subsequently coated with polydopamine (PDA) and red blood cell membrane. The as-fabricated biomimetic nanoformulations showed an enhanced cell uptake in vitro and the potential to prolong blood circulation in vivo, producing effective synergistic chemotherapy, chemodynamic therapy, and photothermal therapy under the 808 nm laser irradiation. Together, the biomimetic nanoformulations showed a prolonged blood circulation and evasion of immune recognition in vivo to provide a bio-inspired strategy which may have the potential for the multi-synergistic therapy of breast cancer.

Gas Therapy: Generating, Delivery, and Biomedical Applications.

Oxygen (O2 ), nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2 S), and hydrogen (H2 ) with direct effects, and carbon dioxide (CO2 ) with complementary effects on the condition of various diseases are known as therapeutic gases. The targeted delivery and in situ generation of these therapeutic gases with controllable release at the site of disease has attracted attention to avoid the risk of gas poisoning and improve their performance in treating various diseases such as cancer therapy, cardiovascular therapy, bone tissue engineering, and wound healing. Stimuli-responsive gas-generating sources and delivery systems based on biomaterials that enable on-demand and controllable release are promising approaches for precise gas therapy. This work highlights current advances in the design and development of new approaches and systems to generate and deliver therapeutic gases at the site of disease with on-demand release behavior. The performance of the delivered gases in various biomedical applications is then discussed.

Core-shell structured microneedles with programmed drug release functions for prolonged hyperuricemia management.

An appropriate non-oral platform via transdermal delivery of drugs is highly recommended for the treatment of hyperuricemia. Herein, a core-shell structured microneedle patch with programmed drug release functions was designed to regulate serum uric acid (SUA) levels for prolonged hyperuricemia management. The patch was fabricated using a three-step casting method. Allopurinol (AP), an anti-hyperuricemic drug, was encapsulated within the carboxymethyl cellulose (CMC) layer, forming the "shell" of the MNs. The MN's inner core was composed of polyvinylpyrrolidone (PVP) loaded with urate oxidase-calcium peroxide nanoparticles (UOx-CaO2 NPs). When the as-fabricated core-shell structured microneedles were inserted into the skin, the loaded AP was first released immediately to effectively inhibit the production of SUA due to the water solubility of CMC. Subsequently, the internal SUA was further metabolized by UOx, leading to exposure of CaO2 NPs. The sustained release of UOx accompanied by the decomposition of CaO2 NPs contributed to maintaining a state of normal uric acid levels over an extended period. More attractively, uric acid could be oxidized due to the strong oxidant of CaO2, which was beneficial to the continuous consumption of uric acid. In vivo results showed that the as-fabricated MNs exhibited an excellent anti-hyperuricemia effect to reduce SUA levels to the normal state within 3 h and maintain the normouricemia state for 12 h. In addition, the levels of creatinine (Cr) and blood urea nitrogen (BUN) in the serum remained within the normal range, and the activities of adenosine deaminase (ADA) and xanthine oxidase (XOD) in the liver were effectively inhabited, mitigating the risk of liver and kidney damage for clinical anti-hyperuricemia management.

Red Blood Cell Membrane-Camouflaged Polydopamine and Bioactive Glass Composite Nanoformulation for Combined Chemo/Chemodynamic/Photothermal Therapy.

Combinations of different therapeutic strategies, including chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT), are needed to effectively address evolving drug resistance and the adverse effects of traditional cancer treatment. Herein, a camouflage composite nanoformulation (TCBG@PR), an antitumor agent (tubercidin, Tub) loaded into Cu-doped bioactive glasses (CBGs) and subsequently camouflaged by polydopamine (PDA), and red blood cell membranes (RBCm), was successfully constructed for targeted and synergetic antitumor therapies by combining CT of Tub, CDT of doped copper ions, and PTT of PDA. In addition, the TCBG@PRs composite nanoformulation was camouflaged with a red blood cell membrane (RBCm) to improve biocompatibility, longer blood retention times, and excellent cellular uptake properties. It integrated with long circulation and multimodal synergistic treatment (CT, CDT, and PTT) with the benefit of RBCms to avoid immune clearance for efficient targeted delivery to tumor locations, producing an "all-in-one" nanoplatform. In vivo results showed that the TCBG@PRs composite nanoformulation prolonged blood circulation and improved tumor accumulation. The combination of CT, CDT, and PTT therapies enhanced the antitumor therapeutic activity, and light-triggered drug release reduced systematic toxicity and increased synergistic antitumor effects.

Flexible All-Solid-State Asymmetric Supercapacitors Based on PPy-Decorated SrFeO3-δ Perovskites on Carbon Cloth.

The defective structure and high oxygen vacancy concentration of SrFeO3-δ perovskite enable fast ion-electron transport, but its low conductivity still hinders the high electrochemical performance. Herein, to enhance the conductivity of SrFeO3-δ-based electrodes, polypyrrole-modified SrFeO3-δ perovskite on carbon cloth (PPy@SFO@CC) has been successfully fabricated by electrodeposition of polypyrrole (PPy) on the surface of SFO@CC. The optimal PPy700@SFO@CC electrode exhibits a specific capacitance of 421 F g-1 at 1 A g-1. It was found that the outside PPy layer not only accelerates the electron transport and ion diffusion but also creates more oxygen vacancies in SrFeO3-δ, enhancing the charge storage performance significantly. Moreover, the NiCo2O4@CC//PPy700@SFO@CC device maintains a specific capacitance of 63.6% after 3000 cycles, which is ascribed to the weak adhesion forces between the active materials and carbon cloth. Finally, the all-solid-state flexible supercapacitor NiCo2O4@CC//PPy700@SFO@CC is constructed with PVA-KOH as the solid electrolyte, delivering an energy density of 16.9 W h kg-1 at a power density of 984 W kg-1. The flexible supercapacitor retains 69% of its specific capacitance after 1000 bending and folding times, demonstrating a certain degree of foldability. The present study opens new avenues for perovskite oxide-based flexible all-solid-state supercapacitors.

Fabrication of carboxymethyl cellulose/hyaluronic acid/polyvinylpyrrolidone composite pastes incorporation of minoxidil-loaded ferulic acid-derived lignin nanoparticles and valproic acid for treatment of androgenetic alopecia.

Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a higher prevalence among young individuals. Traditional oral or subcutaneous injections are often used to treat AGA, however, they may cause severe side-effects and therefore effective treatments for AGA are currently lacking. In this work, to treat AGA, we developed a composite paste system based on minoxidil (MXD)-loaded nanoparticles and valproic acid (VPA) with the assistance of roller-microneedles (roller-MNs). The matrix of composite paste systems is carboxymethyl cellulose (CMC), hyaluronic acid (HA) and polyvinylpyrrolidone (PVP). The roller-MNs can create microchannels in the skin to enhance drug transdermal efficiency. With the combined effects of the stimulation hair follicle (HF) regrowth by upregulating Wnt/beta-catenin of VPA and the mechanical microchannels induced by roller-MNs, the as-prepared composite paste systems successfully boost perifollicular vascularization, and activate hair follicle stem cells, thereby inducing notably faster hair regeneration at a lower administration frequency on AGA mouse model compared with minoxidil. This approach offers several benefits, including the avoidance of efficacy loss due to the liver's first-pass effect associated with oral drug, reduction in the risk of infection from subcutaneous injection, and significant decrease in the side effects of lower-dose MXD.

Optimizing phenol-modified hyaluronic acid for designing shape-maintaining biofabricated hydrogel scaffolds in soft tissue engineering.

In this study, we developed a well-printable biomaterial ink for 3D printing of shape-maintaining hydrogel scaffolds. The hydrogel base comprised tyramine-modified hyaluronic acid (HA-Tyr) and gelatin methacrylate (GelMA) and was dually cross-linked. Using the Box-Behnken design, we explored how varying the ink composition affected fiber formation and shape preservation. By adjusting the polymer ratios, we produced a stable hydrogel with varying responses, from a viscous liquid to a thick gel, and optimized 3D scaffolds that were structurally stable both during and after printing, offering precision and flexibility. Our ink exhibited shear-thinning behavior and high swelling capacity, as well as ECM-like characteristics and biocompatibility, making it an ideal candidate for soft tissues matrices with storage modulus of around 300 Pa. Animal trials and CAM assays confirmed its biocompatibility and integration with host tissue.

Injectable Zn2+ and Paeoniflorin Release Hydrogel for Promoting Wound Healing.

As more and more superbugs emerge, wounds are struggling to heal due to the inflammation that accompanies infection. Therefore, there is an urgent need to reduce the abuse of antibiotics and find nonantibiotic antimicrobial methods to counter infections to accelerate wound healing. In addition, common wound dressings struggle to cover irregular wounds, causing bacterial invasion or poor drug release, which reduces the wound healing rate. In this study, Chinese medicinal monomer paeoniflorin which can inhibit inflammation is loaded in mesoporous zinc oxide nanoparticles (mZnO), while Zn2+ released from mZnO degradation can kill bacteria and facilitate wound healing. The drug-loaded mZnO was encapsulated by a hydrogel formed from oxidized konjac glucomannan and carboxymethyl chitosan via rapid Schiff base reaction to obtain an injectable drug-releasing hydrogel wound dressing. The immediate-formation hydrogel allows the dressing to cover any wound shape. In vitro and in vivo studies have demonstrated that the dressing has good biocompatibility and superior antibacterial properties, which can promote wound healing and tissue regeneration by promoting angiogenesis and collagen production, providing a promising perspective for the further development of multifunctional wound dressings.

Click chemistry for 3D bioprinting.

Bioinks are employed in the fabrication of 3D scaffolds containing cells and macromolecules that can be applied in regenerative medicine. The use of such bioinks facilitates the controlled introduction and localization of macromolecules, bioactives and cells for the biofabrication of living tissues. To enable the successful preparation of the bioinks, strategies involving the use of so-called cross linkers, which may be ionic, chemical, photo-etc. based, are employed. Some of these strategies such as the use of glutaraldehyde as a crosslinker or harsh crosslinking conditions may however compromise the cytocompatibility of the bioink. To circumvent this challenge, the employment of click chemistry technology has been proposed. This is because, click chemistry can enable the preparation of well-tuned bioinks in the absence of problematic cross-linkers, while ensuring that favorable gelation rate, degradation rate, and cell viability properties of the bioinks are not compromised. Indeed, the bio-orthogonal nature of click chemistry has been suggested to enhance the maintenance of high cell viability in scaffolds. In this regard, the current study explored the potential of using different click chemistries in specific bioprinting techniques. Major bioinks produced using click chemistry were also identified, with existing challenges and future trends discussed. It is anticipated that this review will be invaluable to the tissue engineering field by providing an important resource for bioengineers and a basis of future decisions regarding the selection of the preferred click chemistry for specific bioink functionalities.

Regenerated silk fibroin and alginate composite hydrogel dressings loaded with curcumin nanoparticles for bacterial-infected wound closure.

It is important to treat a bacterial-infected wound with a hydrogel dressing due to its excellent biocompatibility and extracellular matrix mimicking structure. In this work, the antibacterial curcumin nanoparticles (Cur-NPs) loaded silk fibroin and sodium alginate (SF/SA) composite hydrogels have been developed as dressings for bacterial-infected wound closure. The as-prepared composite hydrogel dressings exhibited excellent biocompatibility and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro. In addition, the composite hydrogel dressings showed good tissue adhesive strength because of their high viscosity and abundance of amino groups distributed on SF, which can form multi-aldehyde polysaccharides with the tissue surface. The porous 3D structure of the composite hydrogel dressings facilitated the absorption of exudate from the wound site and promoted the fusion of cellular nutrients and metabolites. In the full-thickness skin defect model with and without bacterial infection, the Cur-NPs loaded SF/SA composite hydrogel dressings prominently improves the closure of bacterial-infected wounds by improving cell proliferation, anti-inflammatory properties, vascular remodeling, and collagen deposition.