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Journal of Controlled Release :... Dec 2023Adipose-derived mesenchymal stem cell-derived small extracellular vesicles (Ad-MSC-sEVs/AMEs) combined with scaffold materials are used in tissue-engineered bladders;...
Negatively charged bladder acellular matrix loaded with positively charged adipose-derived mesenchymal stem cell-derived small extracellular vesicles for bladder tissue engineering.
Adipose-derived mesenchymal stem cell-derived small extracellular vesicles (Ad-MSC-sEVs/AMEs) combined with scaffold materials are used in tissue-engineered bladders; however, the lack of retention leads to limited distribution of AMEs in the scaffold areas and low bioavailability of AMEs after bladder reconstruction. To improve retention of AMEs, we developed a novel strategy that modifies the surface charge of the bladder acellular matrix (BAM) via oxidative self-polymerization of dopamine-reducing graphene oxide (GO) and AMEs using ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD). We evaluated two BAM surface modification methods and evaluated the biocompatibility of materials and PPD and electrostatic adherence effects between PPD-modified AMEs and rGO-PDA/BAM in vivo and in vitro. Surface modification increased retention of AMEs, enhanced regeneration of bladder structures, and increased electrical conductivity of rGO-PDA/BAM, thereby improving bladder function recovery. RNA-sequencing revealed 543 miRNAs in human AMEs and 514 miRNAs in rat AMEs. A Venn diagram was used to show target genes of miRNA with the highest proportion predicted by the four databases; related biological processes and pathways were predicted by KEGG and GO analyses. We report a strategy for improving bioavailability of AMEs for bladder reconstruction and reveal that enriched miR-21-5p targets PIK3R1 and activates the PI3K/Akt pathway to promote cell proliferation and migration.
Topics: Rats; Humans; Animals; Tissue Engineering; Urinary Bladder; Phosphatidylinositol 3-Kinases; Extracellular Matrix; Mesenchymal Stem Cells; MicroRNAs; Extracellular Vesicles
PubMed: 37944669
DOI: 10.1016/j.jconrel.2023.10.048 -
Biomaterials Research Sep 2023Drug-resistant bacterial infections in chronic wounds are a persistent issue, as they are resistant to antibiotics and can cause excessive inflammation due to generation...
BACKGROUND
Drug-resistant bacterial infections in chronic wounds are a persistent issue, as they are resistant to antibiotics and can cause excessive inflammation due to generation of reactive oxygen species (ROS). An effective solution would be to not only combat bacterial infections but also scavenge ROS to relieve inflammation at the wound site. Scaffolds with antioxidant properties are attractive for their ability to scavenge ROS, and there is medical demand in developing antioxidant enzyme-mimicking nanomaterials for wound healing.
METHODS
In this study, we fabricated copper-coordination polymer nanoparticles (Cu-CPNs) through a self-assembly process. Furthermore, ε-polylysine (EPL), an antibacterial and cationic polymer, was integrated into the Cu-CPNs structure through a simple one-pot self-assembly process without sacrificing the glutathione peroxidase (GPx) and superoxide dismutase (SOD)-mimicking activity of Cu-CPNs.
RESULTS
The resulting Cu-CPNs exhibit excellent antioxidant propertiesin mimicking the activity of glutathione peroxidase and superoxide dismutase and allowing them to effectively scavenge harmful ROS produced in wound sites. The in vitro experiments showed that the resulting Cu-CPNs@EPL complex have superior antioxidant properties and antibacterial effects. Bacterial metabolic analysis revealed that the complex mainly affects the cell membrane integrity and nucleic acid synthesis that leads to bacterial death.
CONCLUSIONS
The Cu-CPNs@EPL complex has impressive antioxidant properties and antibacterial effects, making it a promising solution for treating drug-resistant bacterial infections in chronic wounds. The complex's ability to neutralize multiple ROS and reduce ROS-induced inflammation can help relieve inflammation at the wound site. Schematic illustration of the ROS scavenging and bacteriostatic function induced by Cu-CPNs@EPL nanozyme in the treatment of MRSA-infected wounds.
PubMed: 37723499
DOI: 10.1186/s40824-023-00429-z -
Bioactive Materials Jul 2023Current treatments for full-thickness skin injuries are still unsatisfactory due to the lack of hierarchically stimulated dressings that can integrate the rapid...
Current treatments for full-thickness skin injuries are still unsatisfactory due to the lack of hierarchically stimulated dressings that can integrate the rapid hemostasis, inflammation regulation, and skin tissue remodeling into the one system instead of single-stage boosting. In this work, a multilayer-structured bioactive glass nanopowder (BGN@PTE) is developed by coating the poly-tannic acid and ε-polylysine onto the BGN facile layer-by-layer assembly as an integrative and multilevel dressing for the sequential management of wounds. In comparison to BGN and poly-tannic acid coated BGN, BGN@PTE exhibited the better hemostatic performance because of its multiple dependent approaches to induce the platelet adhesion/activation, red blood cells (RBCs) aggregation and fibrin network formation. Simultaneously, the bioactive ions from BGN facilitate the regulation of the inflammatory response while the poly-tannic acid and antibacterial ε-polylysine prevent the wound infection, promoting the wound healing during the inflammatory stage. In addition, BGN@PTE can serve as a reactive oxygen species scavenger, alleviate the oxidation stress in wound injury, induce the cell migration and angiogenesis, and promote the proliferation stage of wound repair. Therefore, BGN@PTE demonstrated the significantly higher wound repair capacity than the commercial bioglass dressing Dermlin™. This multifunctional BGN@PTE is a potentially valuable dressing for full-thickness wound management and may be expected to extend to the other wounds therapy.
PubMed: 36844363
DOI: 10.1016/j.bioactmat.2023.01.019 -
Journal of the Mechanical Behavior of... Sep 2023The aim was to quantify effects of polylysine (PLS, 2 or 5 wt%) and monocalcium phosphate (MCP, 4 or 8 wt%) on properties of dental composites.
OBJECTIVES
The aim was to quantify effects of polylysine (PLS, 2 or 5 wt%) and monocalcium phosphate (MCP, 4 or 8 wt%) on properties of dental composites.
METHODS
Light-activated, lower surface polymerisation kinetics versus sample depth (1-4 mm) of 4 formulations were quantified using ATR-FTIR. Water sorption and solubility (at 1 week) were assessed following ISO/4049. PLS release (over 1 month) and biaxial flexural strength (over 6 months) of fully-cured, water-immersed, 1 mm thick discs were determined. Surface mineral precipitation, following immersion in simulated body fluid (SBF), was assessed by SEM. Z250 was used as a conventional composite comparator.
RESULTS
With 40s light exposure, increasing depth (from 1 to 4 mm) led to enhanced delay before polymerisation (from 3 to 17s) and decreased final conversion (72-66%) irrespective of PLS and MCP level. Increasing PLS and MCP raised solubility (4-13 μg/mm). Water sorption (between 32 and 55 μg/mm) and final PLS release (8-13% of disc content) were raised primarily by increasing PLS. Higher PLS also reduced strength. Strength reached minimum values (69-94 MPa) at 3 months. Surface mineral deposition was enhanced by increased MCP. For Z250, polymerisation delays (3-6s) and final conversions (55-54%) at 1-4 mm depth, solubility (0 μg/mm), water sorption (16 μg/mm) and strength (180 MPa) were all significantly different.
CONCLUSION
Delay time increased whilst final conversion decreased with thicker samples. Higher PLS enhances its percentage release, but lower level is required to keep water sorption, solubility and mechanical properties within ISO 4049 recommendations. Doubling MCP raises solubility and enhances minerals reprecipitation with minimal mechanical property compromise.
Topics: Polylysine; Composite Resins; Materials Testing; Solubility; Phosphates; Water; Surface Properties; Dental Materials
PubMed: 37499523
DOI: 10.1016/j.jmbbm.2023.106039 -
Food Science & Nutrition Mar 2024In order to evaluate the effects of chitosan, ε-polylysine, and collagen on the preservation properties of refrigerated , samples were tested with different treatments...
In order to evaluate the effects of chitosan, ε-polylysine, and collagen on the preservation properties of refrigerated , samples were tested with different treatments for 10 days, namely chitosan, ε-polylysine and collagen (CH + ε-PL + CA), chitosan and ε-polylysine (CH + ε-PL), chitosan and collagen (CH + CA), ε-polylysine and collagen (ε-PL + CA), and the uncoated sample (CK). The results demonstrated that the bio-coating exhibited better preservation effects. The CH + ε-PL + CA, CH + ε-PL, CH + CA, ε-PL + CA treatments could significantly inhibit bacterial growth and retard the increase of total volatile base nitrogen (TVB-N), 2-thiobarbituric acid (TBA), K-value, and total viable counts (TVC) in fillets. The pH of all samples decreased and reached its lowest value on day 6, then increased significantly at the end of the experiment ( < .05). Water-holding capacity (WHC) of all the groups decreased continuously throughout storage, and CK reached 66.03% on day 6, which is significantly lower than CH + ε-PL + CA, CH + ε-PL, CH + CA, and ε-PL + CA ( < .05). On the contrary, the sensory scores of CH + ε-PL + CA, CH + ε-PL, CH + CA, and ε-PL + CA were significantly higher than the control, and the score of CH + ε-PL + CA ( < .05) was the best among all the groups. In terms of texture, CH + PL + CA also showed less cell shrinkage and tighter muscle fiber arrangement compared to other treatments. To sum up, the CH + PL + CA bio-coating proved to be a promising method for maintaining the storage quality of under refrigerated storage conditions.
PubMed: 38455186
DOI: 10.1002/fsn3.3916 -
Bioactive Materials Apr 2024Wound management is an important issue that places enormous pressure on the physical and mental health of patients, especially in cases of infection, where the increased...
Wound management is an important issue that places enormous pressure on the physical and mental health of patients, especially in cases of infection, where the increased inflammatory response could lead to severe hypertrophic scars (HSs). In this study, a hydrogel dressing was developed by combining the high strength and toughness, swelling resistance, antibacterial and antioxidant capabilities. The hydrogel matrix was composed of a double network of polyvinyl alcohol (PVA) and agarose with excellent mechanical properties. Hyperbranched polylysine (HBPL), a highly effective antibacterial cationic polymer, and tannic acid (TA), a strong antioxidant molecule, were added to the hydrogel as functional components. Examination of antibacterial and antioxidant properties of the hydrogel confirmed the full play of the efficacy of HBPL and TA. In the studies of methicillin-resistant (MRSA) infection, the hydrogel had shown obvious promotion of wound healing, and more profoundly, significant suppression of scar formation. Due to the common raw materials and simple preparation methods, this hydrogel can be mass produced and used for accelerating wound healing while preventing HSs in infected wounds.
PubMed: 38261887
DOI: 10.1016/j.bioactmat.2023.12.019 -
Bioactive Materials Jul 2023Native-like endothelium regeneration is a prerequisite for material-guided small-diameter vascular regeneration. In this study, a novel strategy is proposed to achieve...
Native-like endothelium regeneration is a prerequisite for material-guided small-diameter vascular regeneration. In this study, a novel strategy is proposed to achieve phase-adjusted endothelial healing by step-wise modification of parallel-microgroove-patterned (i.e., micropatterned) nanofibers with polydopamine-copper ion (PDA-Cu) complexes, polylysine (PLys) molecules, and Cys-Ala-Gly (CAG) peptides (CAG@PLys@PDA-Cu). Using electrospun poly(-lactide--caprolactone) random nanofibers as the demonstrating biomaterial, step-wise modification of CAG@PLys@PDA-Cu significantly enhanced substrate wettability and protein adsorption, exhibited an excellent antithrombotic surface and outstanding phase-adjusted capacity of endothelium regeneration involving cell adhesion, endothelial monolayer formation, and the regenerated endothelium maturation. Upon implantation for segmental replacement of rabbit carotid arteries, CAG@PLys@PDA-Cu modified grafts (2 mm inner diameter) with micropatterns on inner surface effectively accelerated native-like endothelium regeneration within 1 week, with less platelet aggregates and inflammatory response compared to those on non-modified grafts. Prolonged observations at 6- and 12-weeks post-implantation demonstrated a positive vascular remodeling with almost fully covered endothelium and mature smooth muscle layer in the modified vascular grafts, accompanied with well-organized extracellular matrix. By contrast, non-modified vascular grafts induced a disorganized tissue formation with a high risk of thrombogenesis. In summary, step-wise modification of CAG@PLys@PDA-Cu on micropatterned nanofibers can significantly promote endothelial healing without inflicting thrombosis, thus confirming a novel strategy for developing functional vascular grafts or other blood-contacting materials/devices.
PubMed: 37056258
DOI: 10.1016/j.bioactmat.2022.07.010 -
Nature Communications May 2024In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed... (Randomized Controlled Trial)
Randomized Controlled Trial
In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.
Topics: Humans; Dendritic Cells; Glioma; Female; Male; Interferons; Middle Aged; Cancer Vaccines; CD8-Positive T-Lymphocytes; Poly I-C; Adult; Toll-Like Receptors; Imidazoles; Aged; Vaccination; Monocytes; Brain Neoplasms; CD4-Positive T-Lymphocytes; Immunotherapy; Toll-Like Receptor Agonists; Carboxymethylcellulose Sodium; Polylysine
PubMed: 38719809
DOI: 10.1038/s41467-024-48073-y -
Food Chemistry: X Oct 2023For a long time, food spoilage posed a severe impairment on food safety and public health. Although chemical preservatives are commonly used to inhibit spoilage/...
For a long time, food spoilage posed a severe impairment on food safety and public health. Although chemical preservatives are commonly used to inhibit spoilage/ pathogenic microbial growth, the disadvantages of a single target, potential toxicity and high dose of use limit the better use of preservatives. In this research, the combination of natural preservatives: Natamycin (Nat), ε-polylysine (ε-PL), and Chitosan (CS) could achieve an excellent antimicrobial effect including bacteria and fungi, and reduce the usage of a single preservative. Compound preservatives could destroy microbial morphology and damage the integrity of the cell wall/membrane by leakage of protein and alkaline phosphatase (AKP). Besides, high-throughput sequencing revealed that compound preservatives could decrease microbial diversity and richness, especially, , , , and . Therefore, the combination of 1/8 × MIC CS, 1/4 × MIC ε-PL, and 1/2 × MIC Nat can achieve an excellent antibacterial effect, providing new ideas for food preservation.
PubMed: 37780335
DOI: 10.1016/j.fochx.2023.100872 -
Journal of Cell Communication and... Sep 2023Ras GTPases are central to cellular signaling and oncogenesis. The three loci of the Ras gene encode for four protein isoforms namely Harvey-Ras (H-Ras), Kirsten-Ras...
Ras GTPases are central to cellular signaling and oncogenesis. The three loci of the Ras gene encode for four protein isoforms namely Harvey-Ras (H-Ras), Kirsten-Ras (K-Ras 4A and 4B), and Neuroblastoma-Ras (N-Ras) which share ~ 80% sequence similarity and used to be considered functionally redundant. The small molecule inhibitors of Ras lack specificity for the isoforms leading to widespread toxicity in Ras-targeted therapeutics. Ras isoforms' tissue-specific expression and selective association with carcinogenesis, embryonic development, and infection suggested their non-redundancy. We show that CD40, an antigen-presenting cell (APC)-expressed immune receptor, induces selective relocation of H-Ras, K-Ras, and N-Ras to the Plasma membrane (PM) lipid rafts, mitochondria, endoplasmic reticulum (ER), but not to the Golgi complex (GC). The two palmitoylated Ras isoforms-H-Ras and N-Ras-have a similar pattern of colocalization into the lipid-rich raft microdomain of the PM at early time points when compared to non-palmitoylated K-Ras (4B) with polylysine residues. CD40-induced trafficking of H-Ras and K-Ras to mitochondria and ER was found to be similar but different from that of N-Ras. Trafficking of all the Ras isoforms to the GC was independent of CD40 stimulation. The receptor-driven trafficking and spatial segregation of H-Ras, K-Ras, and N-Ras imply isoform-specific subcellular signaling platforms for the functional non-redundancy of Ras isoforms. PDB structures have been modified to illustrate various signaling proteins.
PubMed: 37126117
DOI: 10.1007/s12079-023-00747-w