Niclosamide - encapsulated lipid nanoparticles for the reversal of pulmonary fibrosis.

Pulmonary fibrosis (PF) is a serious and progressive fibrotic interstitial lung disease that is possibly life-threatening and that is characterized by fibroblast accumulation and collagen deposition. Nintedanib and pirfenidone are currently the only two FDA-approved oral medicines for PF. Some drugs such as antihelminthic drug niclosamide (Ncl) have shown promising therapeutic potentials for PF treatment. Unfortunately, poor aqueous solubility problems obstruct clinical application of these drugs. Herein, we prepared Ncl-encapsulated lipid nanoparticles (Ncl-Lips) for pulmonary fibrosis therapy. A mouse model of pulmonary fibrosis induced by bleomycin (BLM) was generated to assess the effects of Ncl-Lips and the mechanisms of reversing fibrosis in vivo. Moreover, cell models treated with transforming growth factor ß1 (TGFß1) were used to investigate the mechanism through which Ncl-Lips inhibit fibrosis in vitro. These findings demonstrated that Ncl-Lips could alleviate fibrosis, consequently reversing the changes in the levels of the associated marker. Moreover, the results of the tissue distribution experiment showed that Ncl-Lips had aggregated in the lung. Additionally, Ncl-Lips improved the immune microenvironment in pulmonary fibrosis induced by BLM. Furthermore, Ncl-Lips suppressed the TGFß1-induced activation of fibroblasts and epithelial-mesenchymal transition (EMT) in epithelial cells. Based on these results, we demonstrated that Ncl-Lips is an efficient strategy for reversing pulmonary fibrosis via drug-delivery.

A Smart Stimulation-Deadhesion and Antimicrobial Hydrogel for Repairing Diabetic Wounds Infected with Methicillin-Resistant Staphylococcus aureus.

The healing of chronic diabetic wounds is a common and significant challenge in the medical field. Despite extensive efforts, the development of hydrogel dressings with satisfactory functionality remains an ongoing concern. In this study, a multifunctional hydrogel wound dressing (PAN/Ag-PLG) with adhesion, antibacterial, hemostatic, and other properties, which can effectively repair diabetic wounds infected with methicillin-resistant Staphylococcus aureus (MRSA), is presented. The hydrogel dressing is composed of gallic acid (GA)-functionalized polylysine (PL)-reduced silver nanoparticles (Ag-PLG), oxidized hyaluronic acid (OHA), and cross-linked polyacrylic acid grafted with N-hydrosuccinimide ester. Notably, compared to most conventional wound dressing that lack adhesion or are difficult to remove, the prepared hydrogels exhibit excellent adhesion and mild stimulation-triggered detachment. In vitro and in vivo experiments reveal that the PAN/Ag-PLG hydrogel exhibits outstanding biocompatibility and antibacterial properties and promotes diabetic wound repair by reducing oxidative damage and promoting cell migration and angiogenesis. The smart PAN/Ag-PLG hydrogel reported in this study provides an approach for the potential clinical development of painless antibacterial dressings.

An Injectable Thermosensitive Hydrogel Containing Resveratrol and Dexamethasone-Loaded Carbonated Hydroxyapatite Microspheres for the Regeneration of Osteoporotic Bone Defects.

Bone defects in osteoporosis usually present excessive reactive oxygen species (ROS), abnormal inflammation levels, irregular shapes and impaired bone regeneration ability; therefore, osteoporotic bone defects are difficult to repair. In this study, an injectable thermosensitive hydrogel poly (D, L-lactide)-poly (ethylene glycol)- poly (D, L-lactide) (PLEL) system containing resveratrol (Res) and dexamethasone (DEX) is designed to create a microenvironment conducive to osteogenesis in osteoporotic bone defects. This PLEL hydrogel is injected and filled irregular defect areas and achieving a rapid sol-gel transition in situ. Res has a strong anti-inflammatory effects that can effectively remove excess free radicals at the damaged site, guide macrophage polarization to the M2 phenotype, and regulate immune responses. Additionally, DEX can promote osteogenic differentiation. In vitro experiments showed that the hydrogel effectively promoted osteogenic differentiation of mesenchymal stem cells, removed excess intracellular ROS, and regulated macrophage polarization to reduce inflammatory responses. In vivo experiments showed that the hydrogel promoted osteoporotic bone defect regeneration and modulated immune responses. Overall, this study confirmed that the hydrogel can treat osteoporotic bone defects by synergistically modulating bone damage microenvironment, alleviating inflammatory responses, and promoting osteogenesis; thus, it represents a promising drug delivery strategy to repair osteoporotic bone defects.

An injectable conductive hydrogel with dual responsive release of rosmarinic acid improves cardiac function and promotes repair after myocardial infarction.

Myocardial infarction (MI) causes irreversible damage to the heart muscle, seriously threatening the lives of patients. Injectable hydrogels have attracted extensive attention in the treatment of MI. By promoting the coupling of mechanical and electrical signals between cardiomyocytes, combined with synergistic therapeutic strategies targeting the pathological processes of inflammation, proliferation, and fibrotic remodeling after MI, it is expected to improve the therapeutic effect. In this study, a pH/ROS dual-responsive injectable hydrogel was developed by modifying xanthan gum and gelatin with reversible imine bond and boronic ester bond double crosslinking. By encapsulating polydopamine-rosmarinic acid nanoparticles to achieve on-demand drug release in response to the microenvironment of MI, thereby exerting anti-inflammatory, anti-apoptotic, and anti-fibrosis effects. By adding conductive composites to improve the conductivity and mechanical strength of the hydrogel, restore electrical signal transmission in the infarct area, promote synchronous contraction of cardiomyocytes, avoid induced arrhythmias, and induce angiogenesis. Furthermore, the multifunctional hydrogel promoted the expression of cardiac-specific markers to restore cardiac function after MI. The in vivo and in vitro results demonstrate the effectiveness of this synergistic comprehensive treatment strategy in MI treatment, showing great application potential to promote the repair of infarcted hearts.

An injectable conductive hydrogel restores electrical transmission at myocardial infarct site to preserve cardiac function and enhance repair.

Myocardial infarction (MI) leads to massive cardiomyocyte death and deposition of collagen fibers. This fibrous tissue disrupts electrical signaling in the myocardium, leading to cardiac systolic and diastolic dysfunction, as well as arrhythmias. Conductive hydrogels are a promising therapeutic strategy for MI. Here, we prepared a highly water-soluble conductive material (GP) by grafting polypyrrole (PPy) onto non-conductive gelatin. This component was added to the gel system formed by the Schiff base reaction between oxidized xanthan gum (OXG) and gelatin to construct an injectable conductive hydrogel. The prepared self-healing OGGP3 (3 wt% GP) hydrogel had good biocompatibility, elastic modulus, and electrical conductivity that matched the natural heart. The prepared biomaterials were injected into the rat myocardial scar tissue 2 days after MI. We found that the cardiac function of the rats treated with OGGP3 was improved, making it more difficult to induce arrhythmias. The electrical resistivity of myocardial fibrous tissue was reduced, and the conduction velocity of myocardial tissue was increased. Histological analysis showed reduced infarct size, increased left ventricular wall thickness, increased vessel density, and decreased inflammatory response in the infarcted area. Our findings clearly demonstrate that the OGGP3 hydrogel attenuates ventricular remodeling and inhibits infarct dilation, thus showing its potential for the treatment of MI.

Mussel-inspired injectable chitosan hydrogel modified with catechol for cell adhesion and cartilage defect repair.

Repairing articular cartilage defects is a great challenge due to the poor self-regenerative capability of cartilage. Hydrogel-based tissue engineering has been considered an effective strategy. In this study, inspired by mussel chemistry, catechol-modified chitosan (CS-C) hydrogel was prepared under the catalysis of horseradish peroxidase/hydrogen peroxide (HRP/H2O2) for cartilage defect repair in a rat model. The rheological and swelling properties and biodegradation behavior of the CS-C hydrogel were investigated. Besides, the chondrogenic effect of bone mesenchymal stem cells (BMSCs) within the CS-C hydrogel was also assessed in vitro. Moreover, after injecting in rat cartilage defects, the capability of cartilage repair of the BMSC-laden CS-C hydrogel was evaluated in vivo. The results showed that the rheological property, swelling property and biodegradation behavior of the CS-C hydrogel changed with the concentration of CS-C macromolecules. Besides, the CS-C hydrogel had good biocompatibility with BMSCs and could promote the proliferation and chondrogenic differentiation of BMSCs in vitro. As for cartilage defect repair in vivo, through the evaluation of gross observation and histology, the BMSC-laden CS-C hydrogel showed better reconstruction of hyaline cartilage than the untreated group and CS-C hydrogel only. Therefore, CS-C hydrogel laden with BMSC might be a promising strategy for repairing cartilage defects.

Elytra-Mimetic Aligned Composites with Air-Water-Responsive Self-Healing and Self-Growing Capability.

Room-temperature self-healing and self-growing of the exoskeleton with aligned structures in insects has few analogs in synthetic materials. Insect cuticle, such as elytra in beetles, with a typical lightweight lamellar structure, has shown this capability, which is attributed to the accumulation of phenol oxidase with polyphenol and amine-rich compounds in the hard cuticle. In this study, laminar-structure-based intelligence is imitated by incorporating adaptable and growable pyrogallol (PG)-borax dynamic-covalent bonds into a poly(acrylamide)-clay network. The events that lead to crack formation and water accumulation quickly trigger the deprotection of PG. Subsequently, atmospheric O2, as a regeneration source, activates PG oxidative self-polymerization. Multiple permanent and dynamic cross-links, with the involvement of the sacrificed borax, and initiation of a series of intelligent responses occur. The fabricated composites with an aligned lamellar structure exhibit outstanding characteristics, such as air/water-triggered superstrong adhesion, self-repairing, self-sealing and resealing, and reprocessing. Moreover, the strategy endows the composites with a self-growing capability, which leads to a 4- to 10-fold increase in its strength in an outdoor climate (up to 51 MPa). This study could lead to advances in the development of air/water-responsive composite materials for applications such as adaptive barriers.

Photo-induced carbocation-enhanced charge transport in single-molecule junctions.

We report the first example of photo-induced carbocation-enhanced charge transport in triphenylmethane junctions using the scanning tunneling microscopy break junction (STM-BJ) technique. The electrical conductance of the carbocation state is enhanced by up to 1.5 orders of magnitude compared to the initial state, with stability lasting for at least 7 days. Moreover, we can achieve light-induced reversible conductance switching with a high ON-OFF ratio in carbocation-based single-molecule junctions. Theoretical calculations reveal that the conductance increase is due to a significant decrease of the HOMO-LUMO gap and also the enhanced transmission close to the Fermi levels when the carbocation forms. Our findings encourage continued research toward developing optoelectronics and carbocation-based devices at the single-molecule level.

Mussel-Inspired Flexible, Wearable, and Self-Adhesive Conductive Hydrogels for Strain Sensors.

The latest generation of wearable devices features materials that are flexible, conductive, and stretchable, thus meeting the requirements of stability and reliability. However, the metal conductors that are currently used in various equipments cannot achieve these high performance expectations. Hence, a mussel-inspired conductive hydrogel (HAC-B-PAM) is prepared with a facile approach by employing polyacrylamide (PAM), dopamine-functionalized hyaluronic acid (HAC), borax as a dynamic cross-linker agent, and Li+ and Na+ as conductive ions. HAC-B-PAM hydrogels demonstrate an excellent stretchability (up to 2800%), high tensile toughness (42.4 kPa), self-adhesive properties (adhesion strength to porcine skin of 49.6 kPa), and good self-healing properties without any stimuli at room temperature. Furthermore, the fabricated hydrogel-based strain sensor is sensitive to deformation and can detect human body motion. Multifunctional hydrogels can be assembled into flexible wearable devices with potential applications in the field of electronic skin and soft robotics.