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1.
J Nanobiotechnology ; 22(1): 241, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735933

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. RESULTS: Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. CONCLUSION: It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.


Subject(s)
Fatty Acids, Volatile , Gastrointestinal Microbiome , Limosilactobacillus reuteri , Probiotics , Gastrointestinal Microbiome/drug effects , Probiotics/pharmacology , Humans , Fatty Acids, Volatile/metabolism , Animals , Limosilactobacillus reuteri/metabolism , Mice , Chitosan/chemistry , Alginates/chemistry , Alginates/pharmacology , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Administration, Oral , Colorectal Neoplasms/drug therapy , Cell Line, Tumor , Receptors, G-Protein-Coupled/metabolism , Microgels/chemistry , Mice, Inbred BALB C , Butyric Acid/pharmacology , Butyric Acid/metabolism
2.
Exp Dermatol ; 33(5): e15098, 2024 May.
Article in English | MEDLINE | ID: mdl-38770557

ABSTRACT

Healing of complex wounds requires dressings that must, at least, not hinder and should ideally promote the activity of key healing cells, in particular fibroblasts. This in vitro study assessed the effects of three wound-dressings (a pure Ca2+ alginate: Algostéril®, a Ca2+ alginate + carboxymethylcellulose: Biatain alginate® and a polyacrylate impregnated with lipido-colloid matrix: UrgoClean®) on dermal fibroblast activity. The results showed the pure calcium alginate to be non-cytotoxic, whereas the other wound-dressings showed moderate to strong cytotoxicity. The two alginates stimulated fibroblast migration and proliferation, whereas the polyacrylate altered migration and had no effect on proliferation. The pure Ca2+ alginate significantly increased the TGF-ß-induced fibroblast activation, which is essential to healing. This activation was confirmed by a significant increase in Vascular endothelial growth factor (VEGF) secretion and a higher collagen production. The other dressings reduced these fibroblast activities. The pure Ca2+ alginate was also able to counteract the inhibitory effect of NK cell supernatants on fibroblast migration. These in vitro results demonstrate that tested wound-dressings are not equivalent for fibroblast activation. Only Algostéril was found to promote all the fibroblast activities tested, which could contribute to its healing efficacy demonstrated in the clinic.


Subject(s)
Alginates , Cell Movement , Cell Proliferation , Fibroblasts , Vascular Endothelial Growth Factor A , Wound Healing , Fibroblasts/drug effects , Wound Healing/drug effects , Humans , Alginates/pharmacology , Cell Movement/drug effects , Cell Proliferation/drug effects , Vascular Endothelial Growth Factor A/metabolism , Collagen/metabolism , Bandages , Transforming Growth Factor beta/metabolism , Carboxymethylcellulose Sodium , Cells, Cultured , Killer Cells, Natural/drug effects , Acrylic Resins , Hexuronic Acids , Glucuronic Acid , Skin
3.
ACS Nano ; 18(20): 12917-12932, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38720520

ABSTRACT

Inflammatory bowel diseases (IBDs) refer to multifaceted disorders in the intestinal microenvironment and microbiota homeostasis. In view of the broad bioactivity and high compatibility of polyphenols, there is considerable interest in developing a polyphenol-based collaborative platform to remodel the IBD microenvironment and regulate microbiota. Here, we demonstrated the coordination assembly of nanostructured polyphenols to modify probiotics and simultaneously deliver drugs for IBD treatment. Inspired by the distinctive structure of tannic acid (TA), we fabricated nanostructured pBDT-TA by using a self-polymerizable aromatic dithiol (BDT) and TA, which exhibited excellent antioxidant and anti-inflammatory capability in vitro. We thus coated pBDT-TA and sodium alginate (SA) to the surface of Escherichia coli Nissle 1917 layer by layer to construct the collaborative platform EcN@SA-pBDT-TA. The modified probiotics showed improved resistance to oxidative and inflammatory stress, which resulted in superior colon accumulation and retention in IBD model mice. Further, EcN@SA-pBDT-TA could alleviate dextran sulfate sodium (DSS)-induced colitis by controlling the inflammatory response, repairing intestinal barriers, and modulating gut microbiota. Importantly, EcN@SA-pBDT-TA-mediated IBD drug delivery could achieve an improved therapeutic effect in DSS model mice. Given the availability and functionality of polyphenol and prebiotics, we expected that nanostructured polyphenol-modified probiotics provided a solution to develop a collaborative platform for IBD treatment.


Subject(s)
Inflammatory Bowel Diseases , Nanoparticles , Polyphenols , Probiotics , Tannins , Animals , Probiotics/pharmacology , Probiotics/chemistry , Probiotics/administration & dosage , Polyphenols/chemistry , Polyphenols/pharmacology , Mice , Nanoparticles/chemistry , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/therapy , Tannins/chemistry , Tannins/pharmacology , Mice, Inbred C57BL , Escherichia coli/drug effects , Dextran Sulfate/chemistry , Alginates/chemistry , Alginates/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology
4.
Cryo Letters ; 45(2): 114-121, 2024.
Article in English | MEDLINE | ID: mdl-38557990

ABSTRACT

BACKGROUND: Stem cell-laden hydrogel microcapsules construction is important for a wide application in tissue engineering and cell-based medicine, such as building an ideal immune barrier. Challenges are emerging for effectively storing such microcapsules by cryopreservation, and a large proportion of research has been on the cryopreservation of single cells encapsulated into microcapsules without a core-shell structure. OBJECTIVE: To achieve the effective cryopreservation of stem cell-laden hydrogel microcapsules with a core-shell structure. MATERIALS AND METHODS: A novel core-shell alginate hydrogel encapsulation method was used to produce mesenchymal stem cell-laden microcapsules by microfluidic technique. RESULTS: This microcapsule could inhibit ice formation to achieve vitreous cryopreservation with a low concentration (2 M) of penetrating cryoprotectants. CONCLUSION: Cell laden hydrogel microcapsules may have the potential to be the basis of a new strategy of cell cryopreservation and applications. https://doi.org/10.54680/fr24210110212.


Subject(s)
Hydrogels , Mesenchymal Stem Cells , Hydrogels/pharmacology , Capsules/pharmacology , Cryopreservation/methods , Cryoprotective Agents/pharmacology , Alginates/pharmacology
5.
Acta Biomater ; 180: 244-261, 2024 May.
Article in English | MEDLINE | ID: mdl-38615812

ABSTRACT

Low back pain is a leading cause of disability worldwide, often attributed to intervertebral disc (IVD) degeneration with loss of the functional nucleus pulposus (NP). Regenerative strategies utilizing biomaterials and stem cells are promising for NP repair. Human NP tissue is highly viscoelastic, relaxing stress rapidly under deformation. However, the impact of tissue-specific viscoelasticity on the activities of adipose-derived stem cells (ASC) remains largely unexplored. Here, we investigated the role of matrix viscoelasticity in regulating ASC differentiation for IVD regeneration. Viscoelastic alginate hydrogels with stress relaxation time scales ranging from 100 s to 1000s were developed and used to culture human ASCs for 21 days. Our results demonstrated that the fast-relaxing hydrogel significantly enhanced ASCs long-term cell survival and NP-like extracellular matrix secretion of aggrecan and type-II collagen. Moreover, gene expression analysis revealed a substantial upregulation of the mechanosensitive ion channel marker TRPV4 and NP-specific markers such as SOX9, HIF-1α, KRT18, CDH2 and CD24 in ASCs cultured within the fast-relaxing hydrogel, compared to slower-relaxing hydrogels. These findings highlight the critical role of matrix viscoelasticity in regulating ASC behavior and suggest that viscoelasticity is a key parameter for novel biomaterials design to improve the efficacy of stem cell therapy for IVD regeneration. STATEMENT OF SIGNIFICANCE: Systematically characterized the influence of tissue-mimetic viscoelasticity on ASC. NP-mimetic hydrogels with tunable viscoelasticity and tissue-matched stiffness. Long-term survival and metabolic activity of ASCs are substantially improved in the fast-relaxing hydrogel. The fast-relaxing hydrogel allows higher rate of cell protrusions formation and matrix remodeling. ASC differentiation towards an NP-like cell phenotype is promoted in the fast-relaxing hydrogel, with more CD24 positive expression indicating NP committed cell fate. The expression of TRPV4, a molecular sensor of matrix viscoelasticity, is significantly enhanced in the fast-relaxing hydrogel, indicating ASC sensing matrix viscoelasticity during cell development. The NP-specific ECM secretion of ASC is considerably influenced by matrix viscoelasticity, where the deposition of aggrecan and type-II collagen are significantly enhanced in the fast-relaxing hydrogel.


Subject(s)
Adipose Tissue , Hydrogels , Mesenchymal Stem Cells , Nucleus Pulposus , Regeneration , Hydrogels/chemistry , Hydrogels/pharmacology , Humans , Nucleus Pulposus/cytology , Nucleus Pulposus/metabolism , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Regeneration/drug effects , Adipose Tissue/cytology , Viscosity , Elasticity , Cell Differentiation/drug effects , Cell Survival/drug effects , Alginates/chemistry , Alginates/pharmacology
6.
ACS Biomater Sci Eng ; 10(5): 3232-3241, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38556725

ABSTRACT

Myocardial infarction (MI) is associated with inflammatory reaction, which is a pivotal component in MI pathogenesis. Moreover, excessive inflammation post-MI can lead to cardiac dysfunction and adverse remodeling, emphasizing the critical need for an effective inflammation-regulating treatment for cardiac repair. Macrophage polarization is crucial in the inflammation process, indicating its potential as an adjunct therapy for MI. In this study, we developed an injectable alginate hydrogel loaded with annexin A1 (AnxA1, an endogenous anti-inflammatory and pro-resolving mediator) for MI treatment. In vitro results showed that the composite hydrogel had good biocompatibility and consistently released AnxA1 for several days. Additionally, this hydrogel led to a reduced number of pro-inflammatory macrophages and an increased proportion of pro-healing macrophages via the adenosine monophosphate (AMP)-activated protein kinase (AMPK)-mammalian target of the rapamycin (mTOR) axis. Furthermore, the intramyocardial injection of this composite hydrogel into a mouse MI model effectively modulated macrophage transition to pro-healing phenotypes. This transition mitigated early inflammatory responses and cardiac fibrosis, promoted angiogenesis, and improved cardiac function. Therefore, our study findings suggest that combining biomaterials and endogenous proteins for MI treatment is a promising approach for limiting adverse cardiac remodeling, preventing cardiac damage, and preserving the function of infarcted hearts.


Subject(s)
Alginates , Annexin A1 , Hydrogels , Macrophages , Myocardial Infarction , Animals , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Myocardial Infarction/metabolism , Alginates/chemistry , Alginates/pharmacology , Annexin A1/metabolism , Annexin A1/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Male , Phenotype , RAW 264.7 Cells , AMP-Activated Protein Kinases/metabolism
7.
ACS Biomater Sci Eng ; 10(5): 3188-3202, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38592024

ABSTRACT

Chronic wound repair is a clinical treatment challenge. The development of multifunctional hydrogels is of great significance in the key aspects of treating chronic wounds, including reducing oxidative stress, promoting angiogenesis, and improving the natural remodeling of extracellular matrix and immune regulation. In this study, we prepared a composite hydrogel, sodium alginate (SA)@MnO2/recombinant humanized collagen III (RHC)/mesenchymal stem cells (MSCs), composed of SA, MnO2 nanoparticles, RHC, and MSCs. The hydrogel has high mechanical properties and good biocompatibility. In vitro, SA@MnO2/RHC/MSCs hydrogel effectively enhanced the formation of intricate tubular structures and angiogenesis and showed synergistic effects on cell proliferation and migration. In vivo, the SA@MnO2/RHC/MSCs hydrogel enhanced diabetes wound healing, rapid re-epithelization, favorable collagen deposition, and abundant wound angiogenesis. These findings demonstrated that the combined effects of SA, MnO2, RHC, and MSCs synergistically accelerate healing, resulting in a reduced healing time. These observed healing effects demonstrated the potential of this multifunctional hydrogel to transform chronic wound care and improve patient outcomes.


Subject(s)
Hydrogels , Manganese Compounds , Mesenchymal Stem Cells , Oxides , Wound Healing , Wound Healing/drug effects , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Animals , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Humans , Oxides/chemistry , Oxides/pharmacology , Diabetes Mellitus, Experimental , Cell Proliferation/drug effects , Collagen/chemistry , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , Alginates/chemistry , Alginates/pharmacology , Male , Mice
8.
Biomacromolecules ; 25(5): 3098-3111, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38606583

ABSTRACT

Biodegradable stents are the most promising alternatives for the treatment of cardiovascular disease nowadays, and the strategy of preparing functional coatings on the surface is highly anticipated for addressing adverse effects such as in-stent restenosis and stent thrombosis. Yet, inadequate mechanical stability and biomultifunctionality limit their clinical application. In this study, we developed a multicross-linking hydrogel on the polylactic acid substrates by dip coating that boasts impressive antithrombotic ability, antibacterial capability, mechanical stability, and self-healing ability. Gelatin methacryloyl, carboxymethyl chitosan, and oxidized sodium alginate construct a double-cross-linking hydrogel through the dynamic Schiff base chemical and in situ blue initiation reaction. Inspired by the adhesion mechanism employed by mussels, a triple-cross-linked hydrogel is formed with the addition of tannic acid to increase the adhesion and antibiofouling properties. The strength and hydrophilicity of hydrogel coating are regulated by changing the composition ratio and cross-linking degree. It has been demonstrated in tests in vitro that the hydrogel coating significantly reduces the adhesion of proteins, MC3T3-E1 cells, platelets, and bacteria by 85% and minimizes the formation of blood clots. The hydrogel coating also exhibits excellent antimicrobial in vitro and antiinflammatory properties in vivo, indicating its potential value in vascular intervention and other biomedical fields.


Subject(s)
Anti-Inflammatory Agents , Anticoagulants , Bivalvia , Polyesters , Stents , Animals , Bivalvia/chemistry , Mice , Polyesters/chemistry , Polyesters/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Stents/adverse effects , Anticoagulants/chemistry , Anticoagulants/pharmacology , Gelatin/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Chitosan/chemistry , Chitosan/analogs & derivatives , Chitosan/pharmacology , Alginates/chemistry , Alginates/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Tannins/chemistry , Tannins/pharmacology , Humans , Methacrylates
9.
Bioresour Technol ; 401: 130709, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636877

ABSTRACT

Low-temperature could inhibit the performance of anaerobic granular sludge (AnGS). Quorum sensing (QS), as a communication mode between microorganisms, can effectively regulate AnGS. In this study, a kind of embedded particles (PVA/SA@Serratia) based on signal molecule secreting bacteria was prepared by microbial immobilization technology based on polyvinyl alcohol and sodium alginate to accelerate the recovery of AnGS system after low temperature. Low-temperature shock experiment verified the positive effect of PVA/SA@Serratia on restoring the COD removal rate and methanogenesis capacity of AnGS. Further analysis by metagenomics analysis showed that PVA/SA@Serratia stimulated higher QS activity and promoted the secretion of extracellular polymeric substance (EPS) in AnGS. The rapid construction of EPS protective layer effectively accelerated the establishment of a robust microbial community structure. PVA/SA@Serratia also enhanced multiple methanogenic pathways, including direct interspecies electron transfer. In conclusion, this study demonstrated that PVA/SA@Serratia could effectively strengthen AnGS after low-temperature shock.


Subject(s)
Alginates , Cold Temperature , Polyvinyl Alcohol , Quorum Sensing , Sewage , Alginates/pharmacology , Alginates/chemistry , Polyvinyl Alcohol/chemistry , Sewage/microbiology , Anaerobiosis , Methane/metabolism
10.
Colloids Surf B Biointerfaces ; 238: 113905, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38593680

ABSTRACT

Hemostasis of deep irregular wounds is a severe problem in clinical practice. The development of rapid-acting hemostatic agents for deep and irregular wound is urgently needed. Here, sodium alginate/carboxycellulose/polydopamine (SA/CNF/PDA) microspheres was prepared by reverse emulsification and crosslinking with Ca2+, and SA/CNF/PDA composite hemostatic microspheres with porous structure were obtained by freeze-drying. SA/CNF/PDA composite hemostatic microspheres exhibited excellent porosity and water absorption which could rapidly absorb blood on the wound surface. Moreover, SA/CNF/PDA composite microspheres demonstrated remarkable hemostatic capabilities both in vitro and in vivo. It exhibited strong hemostatic performance in models of mouse tail-break and liver damage. Especially in liver injury model, it was completely hemostatic in 95 s, and blood loss (19.3 mg). The hemostatic efficacy of the SA/CNF/PDA composite microspheres was amplified through the stimulation of both exogenous and endogenous coagulation pathways. Therefore, SA/CNF/PDA composite hemostatic microspheres are suitable for rapid hemostasis of deep irregular wounds which are potential rapid hemostatic material for surgical application.


Subject(s)
Alginates , Hemostasis , Hemostatics , Indoles , Microspheres , Polymers , Alginates/chemistry , Alginates/pharmacology , Animals , Mice , Polymers/chemistry , Polymers/pharmacology , Hemostasis/drug effects , Hemostatics/chemistry , Hemostatics/pharmacology , Indoles/chemistry , Indoles/pharmacology , Male , Porosity
11.
Int J Biol Macromol ; 268(Pt 1): 131594, 2024 May.
Article in English | MEDLINE | ID: mdl-38621568

ABSTRACT

Treating severe peripheral nerve injuries is difficult. Nerve repair with conduit small gap tubulization is a treatment option but still needs to be improved. This study aimed to assess the use of microgels containing growth factors, along with chitosan-based conduits, for repairing nerves. Using the water-oil emulsion technique, microgels of methacrylic alginate (AlgMA) that contained vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were prepared. The effects on rat Schwann cells (RSC96) and human umbilical vein endothelial cells (HUVECs) were evaluated. Chitosan-based conduits were fabricated and used in conjunction with microgels containing two growth factors to treat complete neurotmesis in rats. The results showed that the utilization of dual growth factor microgels improved the migration and decreased the apoptosis of RSC96 cells while promoting the growth and formation of tubes in HUVECs. The utilization of dual growth factor microgels and chitosan-based conduits resulted in notable advancements in the regeneration and myelination of nerve fibers, recovery of neurons, alleviation of muscle atrophy and recovery of neuromotor function and nerve conduction. In conclusion, the use of dual growth factor AlgMA microgels in combination with chitosan-based conduits has the potential to significantly improve the effectiveness of nerve repair.


Subject(s)
Alginates , Chitosan , Human Umbilical Vein Endothelial Cells , Nerve Regeneration , Schwann Cells , Chitosan/chemistry , Chitosan/pharmacology , Alginates/chemistry , Alginates/pharmacology , Animals , Humans , Rats , Nerve Regeneration/drug effects , Schwann Cells/drug effects , Microgels/chemistry , Peripheral Nerve Injuries/drug therapy , Peripheral Nerve Injuries/therapy , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/pharmacology , Vascular Endothelial Growth Factor A/metabolism , Tissue Scaffolds/chemistry , Methacrylates/chemistry , Methacrylates/pharmacology , Cell Movement/drug effects
12.
Int J Nanomedicine ; 19: 3697-3714, 2024.
Article in English | MEDLINE | ID: mdl-38681091

ABSTRACT

Introduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections. Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV-Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied. Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 µM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy. Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.


Subject(s)
Alginates , Anti-Bacterial Agents , Biofilms , Gold , Nanotubes , Polyethylenes , Quaternary Ammonium Compounds , Staphylococcus aureus , Biofilms/drug effects , Gold/chemistry , Gold/pharmacology , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Alginates/chemistry , Alginates/pharmacology , Nanotubes/chemistry , Animals , Mice , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polyethylenes/chemistry , Polyethylenes/pharmacology , Staphylococcal Infections/drug therapy , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/physiology , Cell Line , Microbial Sensitivity Tests , Metal Nanoparticles/chemistry
13.
Int J Biol Macromol ; 267(Pt 2): 131389, 2024 May.
Article in English | MEDLINE | ID: mdl-38582461

ABSTRACT

This work developed Acer tegmentosum extract-mediated silver nanoparticles (AgNPs) loaded chitosan (CS)/alginic acid (AL) scaffolds (CS/AL-AgNPs) to enhance the healing of E. coli-infected wounds. The SEM-EDS and XRD results revealed the successful formation of the CS/AL-AgNPs. FTIR analysis evidenced that the anionic group of AL (-COO-) and cationic amine groups of CS (-NH3+) were ionically crosslinked to form scaffold (CS/AL). The CS/AL-AgNPs exhibited significant antimicrobial activity against both Gram-positive (G+) and Gram-negative (G-) bacterial pathogens, while being non-toxic to red blood cells (RBCs), the hen's egg chorioallantoic membrane (HET-CAM), and a non-cancerous cell line (NIH3T3). Treatment with CS/AL-AgNPs significantly accelerated the healing of E. coli-infected wounds by regulating the collagen deposition and blood parameters as evidenced by in vivo experiments. Overall, these findings suggest that CS/AL-AgNPs are promising for the treatment of infected wounds.


Subject(s)
Acer , Alginates , Anti-Bacterial Agents , Chitosan , Escherichia coli , Metal Nanoparticles , Plant Extracts , Silver , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Metal Nanoparticles/chemistry , Silver/chemistry , Silver/pharmacology , Animals , Wound Healing/drug effects , Escherichia coli/drug effects , Mice , Acer/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , NIH 3T3 Cells , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Alginates/chemistry , Alginates/pharmacology , Escherichia coli Infections/drug therapy , Tissue Scaffolds/chemistry
14.
Int J Biol Macromol ; 267(Pt 2): 131410, 2024 May.
Article in English | MEDLINE | ID: mdl-38582484

ABSTRACT

A complex illness with a current global hazard, colon cancer has many different manifestations. The efficacy of colon cancer therapy can be affected by the bacteria in the digestive tract. It is hypothesised that novel prebiotics like Gum Odina is emerging as preventative therapy to fight chronic gut illnesses by gut microbiota modulatory therapy when compared to traditional intervention. The first-line chemotherapy drug for colon cancer, capecitabine, lacks a carrier that can extend its half-life. Here, we use the prebiotic gum odina - sodium alginate conjugate to create a capecitabine loaded biopolymeric microspheres, which were previously established as excellent tools for colon cancer therapy. The accelerated stability study exhibited that the alteration in physicochemical properties was found to be negligible. When administered orally to mice with colon cancer, capecitabine raises intra-tumoral capecitabine concentration and slows drug elimination in the blood. Optimized formulation improves anti-tumor immunity over free capecitabine and decrease the tumor volume from 8 ±â€¯6.59 mm3 to 5.21 ±â€¯2.79 mm3. This prebiotics based microsphere combine's gut microbiota manipulation with chemotherapy to offer a potentially effective colon cancer treatment.


Subject(s)
Capecitabine , Colonic Neoplasms , Gastrointestinal Microbiome , Microspheres , Prebiotics , Animals , Capecitabine/pharmacology , Mice , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Gastrointestinal Microbiome/drug effects , Alginates/chemistry , Alginates/pharmacology , Biopolymers/chemistry , Biopolymers/pharmacology , Drug Carriers/chemistry
15.
ACS Biomater Sci Eng ; 10(4): 2552-2566, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38450650

ABSTRACT

The wound-healing effect of insulin is well studied and reported. However, prolonged topical application of insulin without compromising its biological activity is still a challenge. In this study, the effect of topically delivered insulin on promoting wound healing in diabetic animals was evaluated. Alginate diamine PEG-g-poly(PEGMA) (ADPM2S2) was the material used for the topical delivery of insulin. ADPM2S2 hydrogels release insulin and strontium ions, and they synergistically act to regulate different phases of wound healing. Insulin was released from the ADPM2S2 hydrogel for a period of 48 h, maintaining its structural stability and biological activity. In vitro studies were performed under high-glucose conditions to evaluate the wound-healing potential of insulin. Insulin-loaded ADPM2S2 hydrogels showed significant improvement in cell migration, proliferation, and collagen deposition, compared to control cells under high-glucose conditions. Immunostaining studies in L929 cells showed a reduction in phospho Akt expression under high-glucose conditions, and in the presence of insulin, the expression increased. The gene expression studies revealed that insulin plays an important role in regulating the inflammatory phase and macrophage polarization, which favors accelerated wound closure. In vivo experiments in diabetic rat excision wounds treated with insulin-loaded ADPM2S2 showed 95% wound closure within 14 days compared with 82% in control groups. Thus, both the in vitro and in vivo results signify the therapeutic potential of topically delivered insulin in wound management under high-glucose conditions.


Subject(s)
Diabetes Mellitus, Experimental , Insulin , Rats , Animals , Insulin/pharmacology , Insulin/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Hydrogels/chemistry , Alginates/pharmacology , Alginates/chemistry , Alginates/therapeutic use , Wound Healing/physiology , Glucose/pharmacology , Glucose/therapeutic use
16.
Food Funct ; 15(7): 3629-3639, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38482590

ABSTRACT

Inflammation and oxidative stress contribute to noncommunicable diseases (NCDs), with macrophages playing pivotal roles. Glycated collagen through Maillard-type glycation holds promise for enhancing anti-inflammatory properties, but its mechanism remains unclear. This study investigates the cellular mechanism and aims to contribute to expanding collagen utilization. Collagen was glycated with alginate oligosaccharide (AO) and glucose (Glc: as a comparative case) at 60 °C and 35% relative humidity for up to 24 h (C-AO and C-Glc, respectively). The anti-inflammatory activities of both C-AO and C-Glc were evaluated using an LPS-stimulated macrophage model. 18 h AO-glycated collagen (C-AO18 h) was found to significantly reduce the production of nitric oxide and proinflammatory cytokines (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß). In contrast, C-Glc did not exhibit enhanced anti-inflammatory activity during any of the glycation periods. The enhanced anti-inflammatory activity of C-AO18 h was attributed to its downregulating effect on LPS receptors (toll-like receptor 4, Tlr4; cluster of differentiation 14, Cd14) and myeloid differentiation primary response 88 (Myd88) mRNA expression, with suppression in receptor expression resulting in decreased phagocytic ability of macrophages against E. coli. In addition, compared with intact collagen, C-AO18 h exhibited improved antioxidant activity in the LPS-stimulated macrophage model, as it significantly upregulated superoxide dismutase (SOD) and catalase (CAT) activities while reducing malondialdehyde (MDA) levels. Overall, this study contributes to the development of collagen-based functional foods for mitigating inflammation and oxidative stress in NCDs.


Subject(s)
Alginates , Lipopolysaccharides , Humans , Lipopolysaccharides/pharmacology , Alginates/pharmacology , Alginates/therapeutic use , Escherichia coli/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Macrophages/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Cytokines/metabolism , Oxidative Stress , Antioxidants/pharmacology
17.
J Biomater Appl ; 38(9): 957-974, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38453252

ABSTRACT

Skin tissue engineering has gained significant attention as a promising alternative to traditional treatments for skin injuries. In this study, we developed 3D hydrogel-based scaffolds, Alginate, incorporating different concentrations of Curcumin and evaluated their properties, including morphology, swelling behavior, weight loss, as well as hemo- and cytocompatibility. Furthermore, we investigated the therapeutic potential of Alginate hydrogel containing different amounts of Curcumin using an in vitro wound healing model. The prepared hydrogels exhibited remarkable characteristics, SEM showed that the pore size of hydrogels was 134.64 µm with interconnected pores, making it conducive for cellular infiltration and nutrient exchange. Moreover, hydrogels demonstrated excellent biodegradability, losing 63.5% of its weight over 14 days. In addition, the prepared hydrogels had a stable release of curcumin for 3 days. The results also show the hemocompatibility of prepared hydrogels and a low amount of blood clotting. To assess the efficacy of the developed hydrogels, 3T3 fibroblast growth was examined during various incubation times. The results indicated that the inclusion of Curcumin at a concentration of 0.1 mg/mL positively influenced cellular behavior. The animal study showed that Alginate hydrogel containing 0.1 mg/mL curcumin had high wound closure(more than 80%) after 14 days. In addition, it showed up-regulation of essential wound healing genes, including TGFß1 and VEGF, promoting tissue repair and angiogenesis. Furthermore, the treated group exhibited down-regulation of MMP9 gene expression, indicating a reduction in matrix degradation and inflammation. The observed cellular responses and gene expression changes substantiate the therapeutic efficacy of prepared hydrogels. Consequently, our study showed the healing effect of alginate-based hydrogel containing Curcumin on skin injuries.


Subject(s)
Curcumin , Hydrogels , Animals , Hydrogels/pharmacology , Curcumin/pharmacology , Alginates/pharmacology , Wound Healing , Gene Expression Profiling
18.
Int J Biol Macromol ; 264(Pt 2): 130771, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38467220

ABSTRACT

Development of the efficient hemostatic materials is an essential requirement for the management of hemorrhage caused by the emergency situations to avert most of the casualties. Such injuries require the use of external hemostats to facilitate the immediate blood clotting. A variety of commercially available hemostats are present in the market but most of them are associated with limitations such as exothermic reactions, low biocompatibility, and painful removal. Thus, fabrication of an ideal hemostatic composition for rapid blood clot formation, biocompatibility, and antimicrobial nature presents a real challenge to the bioengineers. Benefiting from their tunable fabrication properties, alginate-based hemostats are gaining importance due to their excellent biocompatibility, with >85 % cell viability, high absorption capacity exceeding 500 %, and cost-effectiveness. Furthermore, studies have estimated that wounds treated with sodium alginate exhibited a blood loss of 0.40 ± 0.05 mL, compared to the control group with 1.15 ± 0.13 mL, indicating its inherent hemostatic activity. This serves as a solid foundation for designing future hemostatic materials. Nevertheless, various combinations have been explored to further enhance the hemostatic potential of sodium alginate. In this review, we have discussed the possible role of alginate based composite hemostats incorporated with different hemostatic agents, such as inorganic materials, polymers, biological agents, herbal agents, and synthetic drugs. This article outlines the challenges which need to be addressed before the clinical trials and give an overview of the future research directions.


Subject(s)
Hemostatics , Thrombosis , Humans , Hemostatics/pharmacology , Hemostatics/therapeutic use , Biocompatible Materials/pharmacology , Biocompatible Materials/therapeutic use , Alginates/pharmacology , Hemostasis , Blood Coagulation , Hemorrhage/drug therapy
19.
J Appl Biomater Funct Mater ; 22: 22808000241236590, 2024.
Article in English | MEDLINE | ID: mdl-38444166

ABSTRACT

OBJECTIVE: To evaluate the antitumor and antimicrobial properties of an alginate-based membrane (ABM) loaded with bismuth lipophilic nanoparticles (BisBAL NPs) and cetylpyridinium chloride (CPC) on clinically isolated bacteria and a pancreatic cancer cell line. MATERIAL AND METHODS: The BisBAL NP-CPC ABM was characterized using optical and scanning electron microscopy (SEM). The antimicrobial potential was measured using the disk-diffusion assay, and antibiofilm activity was determined through the live/dead assay and fluorescence microscopy. The antitumor activity was analyzed on the pancreatic cell line (Panc 03.27) using the MTT assay and live/dead assay with fluorescence microscopy. RESULTS: After a 24-h exposure (37°C, aerobic conditions), 5 µM BisBAL NP reduced the growth of K. pneumoniae by 77.9%, while 2.5 µM BisBAL NP inhibited the growth of Salmonella, E. faecalis and E. faecium by 82.9%, 82.6%, and 78%, respectively (p < 0.0001). The BisBAL NPs-CPC ABM (at a ratio of 10:1; 500 and 50 µM, respectively) inhibited the growth of all isolated bacteria, producing inhibition halos of 9.5, 11.2, 7, and 10.3 mm for K. pneumoniae, Salmonella, E. faecalis, and E. faecium, respectively, in contrast to the 6.5, 9.5, 8.5, and 9.8 mm obtained with 100 µM ceftriaxone (p < 0.0001). The BisBAL NPs-CPC ABM also reduced bacterial biofilms, with 81.4%, 74.5%, 97.1%, and 79.5% inhibition for K. pneumoniae, E. faecium, E. faecalis, and Salmonella, respectively. Furthermore, the BisBAL NPs-CPC ABM decreased Panc 03.27 cell growth by 76%, compared to 18% for drug-free ABM. GEM-ABM reduced tumoral growth by 73%. The live/dead assay confirmed that BisBAL NPs-CPC-ABM and GEM-ABM were cytotoxic for the turmoral Panc 03.27 cells. CONCLUSION: An alginate-based membrane loaded with BisBAL NP and CPC exhibits dual antimicrobial and antitumoral efficacy. Therefore, it could be applied in cancer treatment and to diminish the occurrence of surgical site infections.


Subject(s)
Anti-Infective Agents , Bismuth , Dimercaprol/analogs & derivatives , Organometallic Compounds , Cetylpyridinium/pharmacology , Anti-Infective Agents/pharmacology , Alginates/pharmacology , Klebsiella pneumoniae
20.
Biomater Sci ; 12(9): 2418-2433, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38511973

ABSTRACT

Bone defects are a common complication of bone diseases, which often affect the quality of life and mental health of patients. The use of biomimetic bone scaffolds loaded with bioactive substances has become a focal point in the research on bone defect repair. In this study, composite scaffolds resembling bone tissue were created using nacre powder (NP) and sodium alginate (SA) through 3D printing. These scaffolds exhibit several physiological structural and mechanical characteristics of bone tissue, such as suitable porosity, an appropriate pore size, applicable degradation performance and satisfying the mechanical requirements of cancellous bone, etc. Then, platelet-rich fibrin (PRF), containing a mass of growth factors, was loaded on the NP/SA scaffolds. This was aimed to fully maximize the synergistic effect with NP, thereby accelerating bone tissue regeneration. Overall, this study marks the first instance of preparing a bionic bone structure scaffold containing NP by 3D printing technology, which is combined with PRF to further accelerate bone regeneration. These findings offer a new treatment strategy for bone tissue regeneration in clinical applications.


Subject(s)
Alginates , Bone Regeneration , Nacre , Platelet-Rich Fibrin , Powders , Printing, Three-Dimensional , Tissue Scaffolds , Alginates/chemistry , Alginates/pharmacology , Bone Regeneration/drug effects , Tissue Scaffolds/chemistry , Nacre/chemistry , Animals , Platelet-Rich Fibrin/chemistry , Tissue Engineering , Humans , Porosity , Bone and Bones/drug effects , Osteogenesis/drug effects
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