3+ coordination cross-linked poly(glycerol sebacate)-copoly(ethylene glycol)-g-catechol and quadruple hydrogen bonding crosslinked ureido-pyrimidinone modified gelatin. It possesses excellent anti-oxidation, NIR/pH responsiveness, and shape adaptation. Additionally, the hydrogel presents rapid self-healing, good tissue adhesion, degradability, photothermal antibacterial activity, and NIR irradiation and/or acidic solution washing-assisted removability. In vivo experiments prove that the hydrogels have good hemostasis of skin trauma and high killing ratio for methicillin-resistant staphylococcus aureus (MRSA) and achieve better wound closure and healing of skin incision than medical glue and surgical suture. In particular, they can significantly promote full-thickness skin defect wound healing by regulating inflammation, accelerating collagen deposition, promoting granulation tissue formation, and vascularization. These on-demand dissolvable and antioxidant physical double-network hydrogel adhesives are excellent multifunctional dressings for treating in vivo MRSA infection, wound closure, and wound healing.
Biodegradable cryogel wound dressing which can stop deep noncompressible hemorrhage and simultaneously promote wound healing is a highly promising biomaterial in clinics. Here, we prepared a series of biodegradable interpenetrating polymer network (IPN) dry cryogel hemostats by cryopolymerization of gelatin and dopamine. The IPN structure of cross-linked gelatin and polydopamine endows the cryogels good injectability, robust mechanical property, and shape memory property. The cryogels showed better whole bloodclotting capacity and more blood cell and platelet adhesion and activation than gauze and gelatin hemostatic sponge. The cryogels present less blood loss and shorter hemostasis time than gauze and gelatin hemostatic sponges in the mouse liver trauma model, rat liver incision model, and rabbit liver cross incision model. Especially, the hemostatic effect of the cryogel on deep narrow noncompressible hemorrhage was determined by the rabbit liver defect deep narrow noncompressible hemorrhage model. The cryogel rapidly stopped deep massive noncompressible hemorrhage in the swine subclavian artery and vein complete transection model. Besides, the component of polydopamine endows cryogels with excellent antioxidant activity and NIR irradiationassisted photothermal antibacterial ability. Gelatin/dopamine cryogels were more effective in promoting wound healing than Tegaderm films. The developed biodegradable cryogels with a simple preparation process and low cost and which can be easily carried and used present huge potential as novel wound dressing for rapid hemostasis and promoting wound healing.
Adult neurogenesis in the dentate gyrus of the hippocampus is regulated by specific microglia groups and functionally implicated in behavioral responses to stress. However, the role of microglia in hippocampal neurogenesis and stress resilience remains unclear. We identified interleukin 4 (IL4)–driven microglia characterized by high expression of Arg1, which is critical in maintaining hippocampal neurogenesis and stress resistance. Decreasing Arg1+ microglia in the hippocampus by knocking down the microglial IL4R suppressed hippocampal neurogenesis and enhanced stress vulnerability. Increasing Arg1+ microglia in the hippocampus by enhancing IL4 signaling restored hippocampal neurogenesis and the resilience to stress-induced depression. Brain-derived neurotrophic factor (BDNF) was found necessary for the proneurogenesis effects of IL4-driven microglia. Together, our findings suggest that IL4-driven microglia in the hippocampus trigger BDNF-dependent neurogenesis responding to chronic stress, helping protect against depressive-like symptoms. These findings identify the modulation of a specific microglial phenotype as a treatment strategy for mood disorders.
Until now there has been no fundamental theory applicable for biodegradable metals (BMs). First, this paper optimizes the definition of BMs given in 2014. Second, the dual criteria of biodegradability and biocompatibility are proposed for BMs, and all metallic elements in the periodic table with accessible data are screened on the basis of these criteria. Regarding biodegradability, electrode potential, reactivity series, galvanic series, Pilling–Bedworth ratio, and Pourbaix diagrams are all adopted as parameters to classify the degradable and nondegradable nature of a material, especially in a physiological environment. Considering the biocompatibility at different levels, cellular biocompatibility, tissue biocompatibility, and human/clinical related biocompatibility parameters are put forward to comprehensively evaluate the biosafety of BMs. Third, for the material design of BMs, mechanical properties, chemical properties, physical properties and biological properties should be considered and balanced to guarantee that the degradation behavior of BMs match well with a tissue regeneration/repair procedure as the function of time and spatial location. Besides the selected metallic elements, some nonmetallic elements are selected as suitable alloying elements for BMs. Finally, five classification/research directions for future BMs are proposed: biodegradable pure metals, crystalline alloys, bulk metallic glasses, high entropy alloys, and metal matrix composites.
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