Developing injectable nanocomposite conductive hydrogel dressings with multifunctions including adhesiveness, antibacterial, and radical scavenging ability and good mechanical property to enhance full‐thickness skin wound regeneration is highly desirable in clinical application. Herein, a series of adhesive hemostatic antioxidant conductive photothermal antibacterial hydrogels based on hyaluronic acid‐graft‐dopamine and reduced graphene oxide (rGO) using a H2O2/HPR (horseradish peroxidase) system are prepared for wound dressing. These hydrogels exhibit high swelling, degradability, tunable rheological property, and similar or superior mechanical properties to human skin. The polydopamine endowed antioxidant activity, tissue adhesiveness and hemostatic ability, self‐healing ability, conductivity, and NIR irradiation enhanced in vivo antibacterial behavior of the hydrogels are investigated. Moreover, drug release and zone of inhibition tests confirm sustained drug release capacity of the hydrogels. Furthermore, the hydrogel dressings significantly enhance vascularization by upregulating growth factor expression of CD31 and improve the granulation tissue thickness and collagen deposition, all of which promote wound closure and contribute to a better therapeutic effect than the commercial Tegaderm films group in a mouse full‐thickness wounds model. In summary, these adhesive hemostatic antioxidative conductive hydrogels with sustained drug release property to promote complete skin regeneration are an excellent wound dressing for full‐thickness skin repair.

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.

As the abuse of antibiotics continues to increase, the emergence of antibiotic resistance and unknown drug-resistant bacterial infections pose a great threat on people worldwide. In this work, we aimed to develop a series of injectable antimicrobial conductive hydrogels based on glycidyl methacrylate functionalized quaternized chitosan (QCSG), gelatin methacrylate (GM), and graphene oxide (GO) for drug-resistant bacterial disinfection and infectious wound healing. The rheology, morphology, mechanical properties, and electrical and photothermal properties of the hydrogels were characterized. Furthermore, the good in vitro and in vivo intrinsic antibacterial, photothermal antibacterial, and antibiotics released antibacterial properties of this multiantibacterial hydrogel were verified. The good biocompatibility of these hydrogels was also investigated by cytocompatibility, hemocompatibility, and histocompatibility tests. In the drug-resistant Methicillin-resistant Staphylococcus aureus (MRSA) infected mouse full-thickness defect model, the wound closure rate, the length of dermal tissue gap, number of blood vessels and hair follicles in hematoxylin-eosin (HE) staining, the amount of collagen in Masson staining, and the related cytokines for the expression of inflammation (interleukin-6, IL-6) and regeneration of blood vessels (vascular endothelial growth factor, VEGF) in immunofluorescence were all further studied. All the results demonstrated the better wound healing effect of these multiantibacterial injectable conductive hydrogel in infectious skin tissue defect repair, indicating their great potential for infected wound healing.

Human mesenchymal stem cells (hMSCs) can be readily isolated from bone marrow and differentiate into multiple tissues, making them a promising target for future cell and gene therapy applications. The low frequency of hMSCs in bone marrow necessitates their isolation and expansion in vitro prior to clinical use, but due to senescence-associated growth arrest during culture, limited cell numbers can be generated. The lifespan of hMSCs has been extended by ectopic expression of human telomerase reverse transcriptase (hTERT) using retroviral vectors. Since malignant transformation was observed in hMSCs and retroviral vectors cause insertional mutagenesis, we ectopically expressed hTERT using lentiviral gene transfer. Single-cell-derived hMSC clones expressing hTERT did not show malignant transformation in vitro and in vivo after extended culture periods. There were no changes observed in the expression of tumour suppressor genes and karyotype. Cultured hMSCs lack telomerase activity, but it was significantly increased by ectopic expression of hTERT. HTERT expression prevented hMSC senescence and the cells showed significantly higher and unlimited proliferation capacity. Even after an extended culture period, hMSCs expressing hTERT preserved their stem cells character as shown by osteogenic, adipogenic and chon-drogenic differentiation. In summary, extending the lifespan of human mesenchymal stem cells by ectopic expression of hTERT using lentiviral gene transfer may be an attractive and safe way to generate appropriate cell numbers for cell and gene therapy applications.

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Pregnancy loss occurs in about 15% of clinically recognized pregnancies, and defective maternal-fetal immune tolerance contributes to more than 50% of these events. We found that signaling by the type I membrane protein T cell immunoglobulin and mucin-containing protein 3 (Tim-3) in natural killer (NK) cells had an essential protective role during early pregnancy. Tim-3 on peripheral NK (pNK) cells was transiently increased in abundance during the first trimester of pregnancy, which depended on interleukin-4 (IL-4)-signal transducer and activator of transcription 6 (STAT6) and progesterone signaling. Tim-3 pNK cells displayed immunosuppressive activities, including the production of anti-inflammatory cytokines and the induction of regulatory T cells (T) in a transforming growth factor-β1 (TGF-β1)-dependent manner. Tim-3 on pNK cells was stimulated by its ligand galectin-9 (Gal-9), leading to signaling by the kinases c-Jun N-terminal kinase (JNK) and AKT. In recurrent miscarriage (RM) patients, Tim-3 abundance on pNK cells was reduced and the immunosuppressive activity of Tim-3 pNK cells was impaired. Compared to Tim-3 pNK cells from donors with normal pregnancies, RM patient Tim-3 pNK cells exhibited changes in DNA accessibility in certain genetic loci, which were reversed by inhibiting accessible chromatin reader proteins. Furthermore, Tim-3 pNK cells, but not Tim-3 pNK cells, reduced fetal loss in abortion-prone and NK cell-deficient mice. Together, our findings reveal a critical role for Tim-3-Gal-9 signaling-mediated immunoregulation by pNK cells in maternal-fetal immune tolerance and suggest that Tim-3 abundance on pNK cells is a potential biomarker for RM diagnosis.

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Well-defined manganese complexes based on inexpensive, readily available ligands, 2,2':6',2''-terpyridine and its derivatives have been prepared and employed for the selective hydroboration of alkenes, ketones and aldehydes. Highly Markovnikov regioselective hydroboration of styrenes as well as excellent chemoselective hydroboration of ketones over alkenes were achieved, for the first time, by an earth-abundant manganese catalyst.