Local Immunomodulation Using an Adhesive Hydrogel Loaded with miRNA‐Laden Nanoparticles Promotes Wound Healing

Chronic wounds are characterized by impaired healing and uncontrolled inflammation, which compromise the protective role of the immune system and may lead to bacterial infection. Upregulation of miR‐223 microRNAs (miRNAs) shows driving of the polarization of macrophages toward the anti‐inflammatory (M2) phenotype, which could aid in the acceleration of wound healing. However, local‐targeted delivery of microRNAs is still challenging, due to their low stability. Here, adhesive hydrogels containing miR‐223 5p mimic (miR‐223*) loaded hyaluronic acid nanoparticles are developed to control tissue macrophages polarization during wound healing processes. In vitro upregulation of miR‐223* in J774A.1 macrophages demonstrates increased expression of the anti‐inflammatory gene Arg‐1 and a decrease in proinflammatory markers, including TNF‐α, IL‐1β, and IL‐6. The therapeutic potential of miR‐223* loaded adhesive hydrogels is also evaluated in vivo. The adhesive hydrogels could adhere to and cover the wounds during the healing process in an acute excisional wound model. Histological evaluation and quantitative polymerase chain reaction (qPCR) analysis show that local delivery of miR‐223* efficiently promotes the formation of uniform vascularized skin at the wound site, which is mainly due to the polarization of macrophages to the M2 phenotype. Overall, this study demonstrates the potential of nanoparticle‐laden hydrogels conveying miRNA‐223* to accelerate wound healing.     

Ultrafine Silver Nanoparticles Embedded in Cyclodextrin Metal‐Organic Frameworks with GRGDS Functionalization to Promote Antibacterial and Wound Healing Application

The challenge of bacterial infection increases the risk of mortality and morbidity in acute and chronic wound healing. Silver nanoparticles (Ag NPs) are a promising new version of conventional antibacterial nanosystem to fight against the bacterial resistance in concern of the drug discovery void. However, there are several challenges in controlling the size and colloidal stability of Ag NPs, which readily aggregate or coalesce in both solid and aqueous state. In this study, a template‐guided synthesis of ultrafine Ag NPs of around 2 nm using water‐soluble and biocompatible γ‐cyclodextrin metal‐organic frameworks (CD‐MOFs) is reported. The CD‐MOF based synthetic strategy integrates AgNO₃ reduction and Ag NPs immobilization in one pot achieving dual functions of reduced particle size and enhanced stability. Meanwhile, the synthesized Ag NPs are easily dispersible in aqueous media and exhibit effective bacterial inhibition. The surface modification of cross‐linked CD‐MOF particles with GRGDS peptide boosts the hemostatic effect that further enhances wound healing in synergy with the antibacterial effect. Hence, the strategy of ultrafine Ag NPs synthesis and immobilization in CD‐MOFs together with GRGDS modification holds promising potential for the rational design of effective wound healing devices.     

Skin‐Inspired Multifunctional Autonomic‐Intrinsic Conductive Self‐Healing Hydrogels with Pressure Sensitivity,Stretchability, and 3D Printability

The advent of conductive self‐healing (CSH) hydrogels, a class of novel materials mimicking human skin, may change the trajectory of the industrial process because of their potential applications in soft robots, biomimetic prostheses, and health‐monitoring systems. Here, the development of a mechanically and electrically self‐healing hydrogel based on physically and chemically cross‐linked networks is reported. The autonomous intrinsic self‐healing of the hydrogel is attained through dynamic ionic interactions between carboxylic groups of poly(acrylic acid) and ferric ions. A covalent cross‐linking is used to support the mechanical structure of the hydrogel. Establishing a fair balance between the chemical and physical cross‐linking networks together with the conductive nanostructure of polypyrrole networks leads to a double network hydrogel with bulk conductivity, mechanical and electrical self‐healing properties (100% mechanical recovery in 2 min), ultrastretchability (1500%), and pressure sensitivity. The practical potential of CSH hydrogels is further revealed by their application in human motion detection and their 3D‐printing performance.     

Green Fabrication of Amphiphilic Quaternized β‐Chitin Derivatives with Excellent Biocompatibility and Antibacterial Activities for Wound Healing

Bacterial infection has always been a great threat to public health, and new antimicrobials to combat it are urgently needed. Here, a series of quaternized β‐chitin derivatives is prepared simply and homogeneously in an aqueous KOH/urea solution, which is a high‐efficiency, energy‐saving, and “green” route for the modification of chitin. The mild reaction conditions keep the acetamido groups of β‐chitin intact and introduce quaternary ammonium groups on the primary hydroxyl at the C‐6 position of the chitin backbone, allowing the quaternized β‐chitin derivatives (QCs) to easily form micelles. These QCs are found to exhibit excellent antimicrobial activities against Escherichia coli, Staphylococcus aureus, Candida albicans, and Rhizopus oryzae with minimum inhibitory concentrations (MICs) of 8, 12, 60, and 40 µg mL^?1, respectively. As a specific highlight, their inherent outstanding biocompatibility and significant accelerating effects on the healing of uninfected, E. coli‐infected, and S. aureus‐infected wounds imply that these novel polysaccharide‐based materials can be used as dressings for clinical skin regeneration, particularly for infected wounds.