Carstensenclark8311

59% against Staphylococcus aureus and the elimination rate of the formed biofilm was as high as 90.3%, so as to achieve low temperature and efficient treatment of bacterial biofilm infection. More importantly, the modified Ti implant accelerated the growth of cell and the healing process of bone tissue due to the released Ca2+ and PO4 3-. In summary, this work combined PTT with quorum-sensing-inhibition strategy provides a new idea for surface functionalization of implant for achieving effective antibacterial and osseointegration capabilities.The dissolution-derived release of bioactive ions from ceramic coatings on metallic implants, despite improving osseointegration, renders a concern on the interfacial breakdown of the metal/coating/bone system during long-term service. Consequently, persistent efforts to seek alternative strategies instead of dissolution-derived activation are pressingly carrying out. Inspired by bone mineral containing ions as Ca2+, Mg2+, Sr2+ and Zn2+, here we hydrothermally grew the quadruple ions co-doped Na2TiO3 nanorod-like coatings. The co-doped ions partially substitute Na+ in Na2TiO3 , and can be efficiently released from cubic lattice via exchange with Na+ in fluid rather than dissolution, endowing the coatings superior long-term stability of structure and bond strength. Regulated by the coatings-conditioned extracellular ions, TLR4-NFκB signalling is enhanced to act primarily in macrophages (MΦs) at 6 h while CaSR-PI3K-Akt1 signalling is potentiated to act predominately since 24 h, triggering MΦs in a M1 response early and then in a M2 response to sequentially secrete diverse cytokines. Acting on endothelial and mesenchymal stem cells with the released ions and cytokines, the immunomodulatory coatings greatly promote Type-H (CD31hiEmcnhi) angiogenesis and osteogenesis in vitro and in vivo, providing new insights into orchestrating insoluble ceramics-coated implants for early vascularized osseointegration in combination with long-term fixation to bone.MG53 is an essential component of the cell membrane repair machinery, participating in the healing of dermal wounds. Here we develop a novel delivery system using recombinant human MG53 (rhMG53) protein and a reactive oxygen species (ROS)-scavenging gel to treat diabetic wounds. Mice with ablation of MG53 display defective hair follicle structure, and topical application of rhMG53 can promote hair growth in the mg53 -/- mice. Cell lineage tracing studies reveal a physiological function of MG53 in modulating the proliferation of hair follicle stem cells (HFSCs). We find that rhMG53 protects HFSCs from oxidative stress-induced apoptosis and stimulates differentiation of HSFCs into keratinocytes. CP21 molecular weight The cytoprotective function of MG53 is mediated by STATs and MAPK signaling in HFSCs. The thermosensitive ROS-scavenging gel encapsulated with rhMG53 allows for sustained release of rhMG53 and promotes healing of chronic cutaneous wounds and hair follicle development in the db/db mice. These findings support the potential therapeutic value of using rhMG53 in combination with ROS-scavenging gel to treat diabetic wounds.A personalized medication regimen provides precise treatment for an individual and can be guided by pre-clinical drug screening. The economical and high-efficiency simulation of the liver tumor microenvironment (TME) in a drug-screening model has high value yet challenging to accomplish. Herein, we propose a simulation of the liver TME with suspended alginate-gelatin hydrogel capsules encapsulating patient-derived liver tumor multicellular clusters, and the culture of patient-derived tumor organoids(PDTOs) for personalized pre-clinical drug screening. The hydrogel capsule offers a 3D matrix environment with mechanical and biological properties similar to those of the liver in vivo. As a result, 18 of the 28 patient-derived multicellular clusters were successfully cultured as PDTOs. These PDTOs, along with hepatocyte growth factor (HGF) of non-cellular components, preserve stromal cells, including cancer-associated fibroblasts (CAFs) and vascular endothelial cells (VECs). They also maintain stable expression of molecular markers and tumor heterogeneity similar to those of the original liver tumors. Drugs, including cabazitaxel, oxaliplatin, and sorafenib, were tested in PDTOs. The sensitivity of PDTOs to these drugs differs between individuals. The sensitivity of one PDTO to oxaliplatin was validated using magnetic resonance imaging (MRI) and biochemical tests after oxaliplatin clinical treatment of the corresponding patient. Therefore, this approach is promising for economical, accurate, and high-throughput drug screening for personalized treatment.Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effective therapeutic tool for repairing bone defects. Although metal-organic framework (MOF) scaffolds are promising strategies for bone tissue regeneration, their potential use for exosome loading remains unexplored. In this study, motivated by the potential advantages of hADSCs-Exos and Mg-GA MOF, we designed and synthesized an exosome-functionalized cell-free PLGA/Mg-GA MOF (PLGA/Exo-Mg-GA MOF) scaffold, taking using of the benefits of hADSCs-Exos, Mg2+, and gallic acid (GA) to construct unique nanostructural interfaces to enhance osteogenic, angiogenic and anti-inflammatory capabilities simultaneously. Our in vitro work demonstrated the beneficial effects of PLGA/Exo-Mg-GA MOF composite scaffolds on the osteogenic effects in human bone marrow-derived mesenchymal stem cells (hBMSCs) and angiogenic effects in human umbilical endothelial cells (HUVECs). Slowly released hADSCs-Exos from composite scaffolds were phagocytosed by co-cultured cells, stabilized the bone graft environment, ensured blood supply, promoted osteogenic differentiation, and accelerated bone reconstruction. Furthermore, our in vivo experiments with rat calvarial defect model showed that PLGA/Exo-Mg-GA MOF scaffolds promoted new bone formation and satisfactory osseointegration. Overall, we provide valuable new insights for designing exosome-coated nanocomposite scaffolds with enhanced osteogenesis property.Regenerating periodontal bone tissues in the aggravated inflammatory periodontal microenvironment under diabetic conditions is a great challenge. Here, a polydopamine-mediated graphene oxide (PGO) and hydroxyapatite nanoparticle (PHA)-incorporated conductive alginate/gelatin (AG) scaffold is developed to accelerate periodontal bone regeneration by modulating the diabetic inflammatory microenvironment. PHA confers the scaffold with osteoinductivity and PGO provides a conductive pathway for the scaffold. The conductive scaffold promotes bone regeneration by transferring endogenous electrical signals to cells and activating Ca2+ channels. Moreover, the scaffold with polydopamine-mediated nanomaterials has a reactive oxygen species (ROS)-scavenging ability and anti-inflammatory activity. It also exhibits an immunomodulatory ability that suppresses M1 macrophage polarization and activates M2 macrophages to secrete osteogenesis-related cytokines by mediating glycolytic and RhoA/ROCK pathways in macrophages. The scaffold induces excellent bone regeneration in periodontal bone defects of diabetic rats because of the synergistic effects of good conductive, ROS-scavenging, anti-inflammatory, and immunomodulatory abilities. This study provides fundamental insights into the synergistical effects of conductivity, osteoinductivity, and immunomodulatory abilities on bone regeneration and offers a novel strategy to design immunomodulatory biomaterials for treatment of immune-related diseases and tissue regeneration.To solve the issue of unsatisfactory recruitment of mesenchymal stem cells (MSCs) around implant in osteoporotic fractures, we fabricated a ROS-responsive system on titanium surface through hydroxyapatite coating and biomolecule grafting. The porous hydroxyapatite and phosphorylated osteogenic growth peptides (p-OGP) were introduced onto titanium surface to synergistically improve osteogenic differentiation of MSCs. After the p-OGP-promoted expression of osteogenic related proteins, the calcium and phosphate ions were released through the degradation of hydroxyapatite and integrated into bone tissues to boost the mineralization of bone matrix. The ROS-triggered release of DNA aptamer (Apt) 19S in the osteoporotic microenvironment guides MSC migration to implant site due to its high affinity with alkaline phosphatase on the membrane of MSCs. Once MSCs reached the implant interface, their osteogenic differentiation potential was enhanced by p-OGP and hydroxyapatite to promote bone regeneration. The study here provided a simple and novel strategy to prepare functional titanium implants for osteoporotic bone fracture repair.The percutaneous device dilemma describes etiological factors, centered around the disrupted epithelial tissue surrounding non-remodelable devices, that contribute to rampant percutaneous device infection. Natural percutaneous organs, in particular their extracellular matrix mediating the "device"/epithelium interface, serve as exquisite examples to inspire longer lasting long-term percutaneous device design. For example, the tooth's imperviousness to infection is mediated by the epithelium directly surrounding it, the junctional epithelium (JE). The hallmark feature of JE is formation of hemidesmosomes, cell/matrix adhesive structures that attach surrounding oral gingiva to the tooth's enamel through a basement membrane. Here, the authors survey the multifaceted functions of the JE, emphasizing the role of the matrix, with a particular focus on hemidesmosomes and their five main components. The authors highlight the known (and unknown) effects dental implant - as a model percutaneous device - placement has on JE regeneration and synthesize this information for application to other percutaneous devices. The authors conclude with a summary of bioengineering strategies aimed at solving the percutaneous device dilemma and invigorating greater collaboration between clinicians, bioengineers, and matrix biologists.Due to the unsatisfactory therapeutic efficacy and inexorable side effects of small molecule antineoplastic agents, extensive efforts have been devoted to the development of more potent macromolecular agents with high specificity. Gelonin is a plant-derived protein toxin that exhibits robust antitumor effect via inactivating ribosomes and inhibiting protein synthesis. Nonetheless, its poor internalization ability to tumor cells has compromised the therapeutic promise of gelonin. In this study, a tumor acidity-responsive intracellular protein delivery system ─ functional gelonin (Trx-pHLIP-Gelonin, TpG) composed of a thioredoxin (Trx) tag, a pH low insertion peptide (pHLIP) and gelonin, was designed and obtained by genetic recombination technique for the first time. TpG could effectively enter into tumor cells under weakly acidic conditions and markedly suppress tumor cell proliferation via triggering cell apoptosis and inhibiting protein synthesis. Most importantly, treatment by intravenous injection into subcutaneous SKOV3 solid tumors in a mouse model showed that TpG was much more effective than gelonin in curtailing tumor growth rates with negligible toxicity. Collectively, our present work suggests that the tumor acidity-targeted delivery manner endowed by pHLIP offers a new avenue for efficient delivery of other bioactive substances to acidic diseased tissues.