Neutrophil Function Conversion Driven by Immune Switchpoint Regulator against Diabetes-Related Biofilm Infections. Advanced materials (Deerfield Beach, Fla.) Reinforced biofilm structures and dysfunctional neutrophils induced by excessive oxidative stress contribute to the refractoriness of diabetes-related biofilm infections (DRBIs). Herein, in contrast to traditional antibacterial therapies, an immune switchpoint-driven neutrophil immune function conversion strategy based on a deoxyribonuclease I loaded vanadium carbide MXene (DNase-I@V C) nanoregulator is proposed to treat DRBIs via biofilm lysis and redirecting neutrophil functions from NETosis to phagocytosis in diabetes. Owing to its intrinsic superoxide dismutase/catalase-like activities, DNase-I@V C effectively scavenges reactive oxygen species (ROS) in a high oxidative stress microenvironment to maintain the biological activity of DNase-I. By increasing the depth of biofilm penetration of DNase-I, DNase-I@V C thoroughly degrades extracellular DNA and neutrophil extracellular traps (NETs) in extracellular polymeric substances, thus breaking the physical barrier of biofilms. More importantly, as an immune switchpoint regulator, DNase-I@V C can skew neutrophil functions from NETosis toward phagocytosis by intercepting ROS-NE/MPO-PAD4 and activating ROS-PI3K-AKT-mTOR pathways in diabetic microenvironment, thereby eliminating biofilm infections. Biofilm lysis and synergistic neutrophil function conversion exert favorable therapeutic effects on biofilm infections in vitro and in vivo. This study serves as a proof-of-principle demonstration of effectively achieving DRBIs with high therapeutic efficacy by regulating immune switchpoint to reverse neutrophil functions. 10.1002/adma.202310320

Multifunctional MXene-doped photothermal microneedles for drug-resistant bacteria-infected wound healing. Biomaterials science Skin injuries and drug-resistant bacterial infections pose serious challenges to human health. It is essential to establish a novel multifunctional platform with good anti-infection and wound-healing abilities. In this study, a new MXene-doped composite microneedle (MN) patch with excellent mechanical strength and photothermal antibacterial and ROS removal properties has been developed for infected wound healing. When the MN tips carrying the MXene nanosheets are inserted into the cuticle of the skin, they will quickly dissolve and subsequently release the nanomaterials into the subcutaneous infection area. Under 808 nm NIR irradiation, the MXene, as a "nano-thermal knife", sterilizes and inhibits bacterial growth through synergistic effects of sharp edges and photothermal antibacterial activity. Furthermore, ROS caused by injury and infection can be cleared by MXene-doped MNs to avoid excessive inflammatory responses. Based on the synergistic antibacterial and antioxidant strategy, the MXene-doped MNs have demonstrated excellent wound-healing properties in an MRSA-infected wound model, such as promoting re-epithelialization, collagen deposition, and angiogenesis and inhibiting the expression of pro-inflammatory factors. Therefore, the multifunctional MXene-doped MN patches provide an excellent alternative for clinical drug-resistant bacteria-infected wound management. 10.1039/d3bm01676e

Artificial Nonenzymatic Antioxidant MXene Nanosheet-Anchored Injectable Hydrogel as a Mild Photothermal-Controlled Oxygen Release Platform for Diabetic Wound Healing. ACS nano Hypoxia, excessive reactive oxygen species (ROS), impaired angiogenesis, lasting inflammation, and bacterial infection, are key problems impeding diabetic wound healing. Particularly, controllable oxygen release and ROS scavenging capacities are critical during the wound healing process. Here, an injectable hydrogel based on hyaluronic acid--dopamine (HA-DA) and polydopamine (PDA) coated TiC MXene nanosheets is developed catalytically cross-linked by an oxyhemoglobin/hydrogen (HbO/HO) system combined with mild photothermal stimulation for diabetic wound healing. HbO not only acts as a horseradish peroxidase-like to catalyze the hydrogel formation but also as an oxygen carrier to controllably release oxygen when activated by the mild heat produced from near-infrared (NIR) irradiation. Specifically, HbO can provide oxygen repeatedly by binding oxygen in the air when the NIR is off. The stable photoresponsive heating behavior of MXene ensures the repeatable oxygen release. Additionally, artificial nonenzymatic antioxidant MXene nanosheets are proposed to scavenge excessive reactive nitrogen species and ROS including HO, O, and OH, keeping the intracellular redox homeostasis and alleviating oxidative stress, and eradicate bacteria to avoid infection. The antioxidant and antibacterial abilities of MXene are further improved by PDA coating, which also promotes the MXene nanosheets cross-linking into the network of the hydrogel. HA-DA molecules endow the hydrogel with the capacity to regulate macrophage polarization from M1 to M2 to achieve anti-inflammation. More importantly, the MXene-anchored hydrogel with multifunctions including tissue adhesion, self-healing, injectability, and hemostasis, combined with mild photothermal stimulation, greatly promotes human umbilical vein endothelial cell proliferation and migration and notably facilitates infected diabetic wound healing. 10.1021/acsnano.1c10575