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Hematopoietic stem cell transplantation (HSCT) is extensively employed in the treatment of hematological malignancies but is markedly constrained by the paucity of hematopoietic stem/progenitor cells (HSPCs). Recent studies have found that marrow adipose tissue (MAT) acts on hematopoiesis through complicated mechanisms. Therefore, the osteo-organoids fabricated in vivo using biomaterials loaded with recombinant human bone morphogenetic protein 2 (rhBMP-2) have been used as models of MAT for our research. To obtain sufficient amounts of therapeutic HSPCs and healthy MAT, we have developed amphiphilic chitosan (AC)-gelatin as carriers of rhBMP-2 to the regulate type conversion of adipose tissue and trap hematopoietic growth factors. Unlike medicine interventions or cell therapies, the traps based on AC not only attenuate the occupancy of adipocytes within the hematopoietic microenvironment while preserving stem cell factor concentrations, but also improve marrow metabolism by promoting MAT browning. In conclusion, this approach increases the proportion of HSPCs in osteo-organoids, and optimizes the composition and metabolic status of MAT. These findings furnish an experimental basis for regulating hematopoiesis in vivo through materials that promote the development of autologous HSPCs. Additionally, this approach presents a theoretical model of rapid adipogenesis for the study of adipose-related pathologies and potential pharmacological targets.
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Background This study investigated the anticoagulant properties of sulfated chitosan derived from the internal bone of the spineless cuttlefish Sepiella inermis. Chitosan, a biopolymer, is used in various biomedical applications including anticoagulation. Sulfation of chitosan enhances its biological activity, making it a potential therapeutic agent. This study explored the efficacy of sulfated chitosan in preventing blood clot formation to provide a novel anticoagulant alternative. Objectives This study aimed to synthesize and characterize the anticoagulant properties of sulfated chitosan extracted from the internal bone of the spineless cuttlefish S. inermis using Fourier Transform Infrared Spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM), and X-Ray Diffraction (XRD) and evaluate the anticoagulant properties of sulfated chitosan extracted from the internal bone of spineless cuttlefish S. inermis. Materials and methods Chitin and chitosan were extracted from the cuttlebone of a specimen of S. inermis, and sulfated chitosan was synthesized by sulfation of chitosan. Sulfated chitosan was subsequently used to evaluate its anticoagulant properties using tests such as activated partial thromboplastin time (APTT) and prothrombin time (PT). Characteristic investigations were conducted, including FTIR, FESEM, and XRD analyses. Results The results of this study suggested the possibility of using S. inermis internal bone as an unconventional source of natural anticoagulant that can be combined with biomedical applications. Anticoagulant activity measured using APTT and PT showed that sulfated chitosan was a strong anticoagulant. Conclusion We examined the anticoagulant activity of S. inermis extract using thrombin and activated partial thromboplastin times. Our results demonstrated the heparin-like anticoagulant action of the extracted sulfated chitosan, suggesting that it may be a great alternative anticoagulant treatment.
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Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.
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Antibacterianos , Regeneración Ósea , Quitosano , Cobre , Fusobacterium nucleatum , Nanopartículas , Periodontitis , Quitosano/química , Quitosano/farmacología , Periodontitis/tratamiento farmacológico , Periodontitis/microbiología , Periodontitis/terapia , Periodontitis/patología , Animales , Antibacterianos/farmacología , Antibacterianos/química , Regeneración Ósea/efectos de los fármacos , Ratas , Cobre/química , Cobre/farmacología , Fusobacterium nucleatum/efectos de los fármacos , Nanopartículas/química , Ratas Sprague-Dawley , Masculino , Sulfatos/química , Sulfatos/farmacología , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Diabetic wound healing is a significant clinical challenge because abnormal immune cells in the wound cause chronic inflammation and impair tissue regeneration. Therefore, regulating the behavior and function of macrophages may be conducive to improving treatment outcomes in diabetic wounds. Herein, sulfated chitosan (26SCS)-containing composite sponges (26SCS-SilMA/Col-330) with well-arranged layers and high porosity were constructed based on collagen and silk fibroin, aiming to induce an appropriate inflammatory response and promote angiogenesis. The results indicated that the ordered topological structure of composite sponges could trigger the pro-inflammatory response of Mφs in the early stage, and rapid release of 26SCS in the early and middle stages (within the concentration range of 1-3 mg/mL) induced a positive inflammatory response; initiated the pro-inflammatory reaction of Mφs within 3 days; shifted M1 Mφs to the M2 phenotype within 3-7 days; and significantly up-regulated the expression of two typical angiogenic growth factors, namely VEGF and PDGF-BB, on day 7, leading to rapid HUVEC migration and angiogenesis. In vivo data also demonstrated that on the 14th day after surgery, the 26SCS-SilMA/Col-330-implanted areas exhibited less inflammation, faster re-epithelialization, more abundant collagen deposition and a greater number of blood vessels in the skin tissue. The composite sponges with higher 26SCS contents (the (5.0) 26SCS-SilMA/Col-330 and the (7.5) 26SCS-SilMA/Col-330) could better orchestrate the phenotype and function of Mφs and facilitate wound healing. These findings highlight that the 26SCS-SilMA/Col-330 sponges developed in this work might have great potential as a novel dressing for the treatment of diabetic wounds.
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Quitosano , Inflamación , Macrófagos , Neovascularización Fisiológica , Cicatrización de Heridas , Animales , Humanos , Masculino , Ratones , Ratas , Angiogénesis , Quitosano/química , Colágeno/química , Diabetes Mellitus Experimental , Fibroínas/química , Células Endoteliales de la Vena Umbilical Humana , Inflamación/patología , Macrófagos/metabolismoRESUMEN
Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, and have limited drug release control. Herein, we developed an ROS-responsive nanocarrier for targeted delivery of the neuroprotective agent rapamycin (RAPA) to mitigate ischemic brain damage. The nanocarrier consisted of a sulfated chitosan (SCS) polymer core modified with a ROS-responsive boronic ester enveloped by a red blood cell membrane shell incorporating a stroke homing peptide. When encountering high levels of intracellular ROS in ischemic brain tissues, the release of SCS combined with RAPA from nanoparticle disintegration facilitates effective microglia polarization and, in turn, maintains blood-brain barrier integrity, reduces cerebral infarction, and promotes cerebral neurovascular remodeling in a mouse stroke model involving transient middle cerebral artery occlusion (tMCAO). This work offers a promising strategy to treat ischemic stroke therapy.
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Barrera Hematoencefálica , Quitosano , Portadores de Fármacos , Accidente Cerebrovascular Isquémico , Nanopartículas , Sirolimus , Animales , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/patología , Ratones , Quitosano/química , Portadores de Fármacos/química , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Sirolimus/farmacología , Sirolimus/química , Sirolimus/uso terapéutico , Nanopartículas/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/uso terapéutico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Polisacáridos/química , Polisacáridos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sulfatos/química , Sulfatos/farmacología , Microglía/efectos de los fármacos , Microglía/metabolismoRESUMEN
Conductive polymers (CPs) are typically insoluble in solvents, and devising biocompatible hydrophilic CPs is challenging and imperative to expand the applications of CPs. Herein, sulfated chitosan (SCS) is used as a green dopant instead of toxic poly(styrene sulfonate) (PSS), and SCS:polypyrrole (SCS:PPy) conductive ink is prepared by in situ polymerization. Due to the complex structure between PPy and SCS polyanion, the synthesized SCS:PPy dispersion forms a well-connected electric pathway and confers superior conductivity, dispersion stability, good film-forming ability, and high electrical stability. As proof of our concept, electrochemical sensing utilizing an SCS:PPy-modified screen-printed carbon electrode (SPCE) was performed towards carbendazim (CBZ). The SCS:PPy on the SPCE surface displayed greater sensitivity to CBZ because the conductive complex structure eased the electrocatalytic action of SCS:PPy by dramatically increasing the current intensity of CBZ oxidation and notably ameliorating stability. The sensor unveils the lowest detection value of 1.02 nM with a linear range of 0.05 to 906 µM for sensing trace CBZ by utilizing the pulse voltammetry technique. Interestingly, this senor shows excellent selectivity towards CBZ due to the formation of substantial interactions between SCS:PPy and CBZ, as demonstrated by molecular simulation studies. Furthermore, this sensor can precisely monitor CBZ in actual fruit and river water samples with satisfactory results. This study sheds light on the design and synthesis of sustainable hydrophilic CPs in the fabrication of sensors.
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Deaths from cancer are widespread worldwide and the numbers continue to increase day by day. During the disease progression of cancer in cells, many of its metabolic activities change. Increased heparanase enzyme release is just one example. Following heparanase enzyme activity, many molecules interact with the remodeling of glycosaminoglycan structures, which triggers the release of different enzymes, cytokines, and growth factors, including fibroblast growth factors (FGF1 and FGF2), vascular endothelial growth factor (VEGF), hepatocyte growth factor, transforming growth factor ß and platelet-derived growth factor. These are the most important factors in metastasis due to the formation of new vascular structures caused by those elements. To reduce tumor growth and metastasis, various drugs have been designed by modifying chitosan and its derivatives. In this study, we used chitosan oligomer (A), sulfated chitosan oligomer (ShCsO) (B), heparin (C), phosphate monomer (D1) of PI-88 and sulfate monomer (D2) of PI-88 as heparanase inhibitors. We modified the chitosan oligomer with chlorosulfonic acid to synthesize ShCsO to investigate its inhibitory effects on human serum heparanase. Also examined were molecular docking; molecular dynamics (MD); adsorption, distribution, metabolism, elimination and toxicity (ADMET); and target prediction. ShCsO decreased enzyme activity at a concentration of 0.0001 mg/mL. The docking scores of A, B and C from in silico studies were -6.254, -6.936 and -6.980 kcal/mol, respectively, and the scores for the two different PI-88 monomers were -5.741 and -5.824 kcal/mol. These results show that ShCsO may be a potential drug candidate for treating cancer.Communicated by Ramaswamy H. Sarma.
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Musculoskeletal injuries and bone defects represent a significant clinical challenge, necessitating innovative approaches for effective bone tissue regeneration. In this study, we investigated the potential of harnessing periosteal stem cells (PSCs) and glycosaminoglycan (GAG)-mimicking materials for in situ bone regeneration. Our findings demonstrated that the introduction of 2-N, 6-O sulfated chitosan (26SCS), a GAG-like polysaccharide, enriched PSCs and promoted robust osteogenesis at the defect area. Mechanistically, 26SCS amplifies the biological effect of endogenous platelet-derived growth factor-BB (PDGF-BB) through enhancing the interaction between PDGF-BB and its receptor PDGFRß abundantly expressed on PSCs, resulting in strengthened PSC proliferation and osteogenic differentiation. As a result, 26SCS effectively improved bone defect repair, even in an osteoporotic mouse model with lowered PDGF-BB level and diminished regenerative potential. Our findings suggested the significant potential of GAG-like biomaterials in regulating PSC behavior, which holds great promise for addressing osteoporotic bone defect repair in future applications.
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With increased diabetes incidence, diabetic wound healing is one of the most common diabetes complications and is characterized by easy infection, chronic inflammation, and reduced vascularization. To address these issues, biomaterials with multifunctional antibacterial, immunomodulatory, and angiogenic properties must be developed to improve overall diabetic wound healing for patients. In our study, we prepared porous poly (L-lactic acid) (PLA) nanofiber membranes using electrospinning and solvent evaporation methods. Then, sulfated chitosan (SCS) combined with polydopamine-gentamicin (PDA-GS) was stepwise modified onto porous PLA nanofiber membrane surfaces. Controlled GS release was facilitated via dopamine self-polymerization to prevent early stage infection. PDA was also applied to PLA nanofiber membranes to suppress inflammation. In vitro cell tests results showed that PLA/SCS/PDA-GS nanofiber membranes immuomodulated macrophage toward the M2 phenotype and increased endogenous vascular endothelial growth factor secretion to induce vascularization. Moreover, SCS-contained PLA nanofiber membranes also showed good potential in enhancing macrophage trans-differentiation to fibroblasts, thereby improving wound healing processes. Furthermore, our in vitro antibacterial studies against Staphylococcus aureus indicated the effective antibacterial properties of the PLA/SCS/PDA-GS nanofiber membranes. In summary, our novel porous PLA/SCS/PDA-GS nanofiber membranes possessing enhanced antibacterial, anti-inflammatory, and angiogenic properties demonstrate promising potential in diabetic wound healing processes.
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Quitosano , Diabetes Mellitus , Nanofibras , Humanos , Porosidad , Factor A de Crecimiento Endotelial Vascular , Poliésteres/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cicatrización de Heridas , Antiinflamatorios , Ácido LácticoRESUMEN
BACKGROUND: Porcine circovirus type 2 (PCV2)-associated diseases are a major problem for the swine industry worldwide. In addition to vaccines, the availability of antiviral polymers provides an efficient and safe option for reducing the impact of these diseases. By virtue of their molecular weight and repetitious structure, polymers possess properties not found in small-molecule drugs. In this perspective, we focus on chitosan, a ubiquitous biopolymer, that adjusts the molecular weight and sulfated-mediated functionality can act as an efficient antiviral polymer by mimicking PCV2-cell receptor interactions. METHODS: Sulfated chitosan (Chi-S) polymers of two molecular weights were synthesized and characterized by FTIR, SEM-EDS and elemental analysis. The Chi-S solutions were tested against PCV2 infection in PK15 cells in vitro and antiviral activity was evaluated by measuring the PCV2 DNA copy number, TCID50 and capsid protein expression, upon application of different molecular weights, sulfate functionalization, and concentrations of polymer. In addition, to explore the mode of action of the Chi-S against PCV2 infection, experiments were designed to elucidate whether the antiviral activity of the Chi-S would be influenced by when it was added to the cells, relative to the time and stage of viral infection. RESULTS: Chi-S significantly reduced genomic copies, TCID50 titers and capsid protein of PCV2, showing specific antiviral effects depending on its molecular weight, concentration, and chemical functionalization. Assays designed to explore the mode of action of the low molecular weight Chi-S revealed that it exerted antiviral activity through impeding viral attachment and penetration into cells. CONCLUSIONS: These findings help better understanding the interactions of PCV2 and porcine cells and reinforce the idea that sulfated polymers, such as Chi-S, represent a promising candidates for use in antiviral therapies against PCV2-associated diseases. Further studies in swine are warranted.
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Quitosano , Infecciones por Circoviridae , Circovirus , Enfermedades de los Porcinos , Animales , Antivirales/metabolismo , Antivirales/farmacología , Proteínas de la Cápside/genética , Quitosano/metabolismo , Quitosano/farmacología , Infecciones por Circoviridae/prevención & control , Circovirus/genética , Peso Molecular , Sulfatos/metabolismo , Porcinos , Replicación Viral/genéticaRESUMEN
The development of blood-interacting surfaces is critical to fabricate biomaterials for medical use, such as prostheses, implants, biosensors, and membranes. For instance, thrombosis is one of the leading clinical problems when polymer-based materials interact with blood. To overcome this limitation is necessary to develop strategies that limit platelets adhesion and activation. In this work, hyaluronan (HA)/chitosan (Chi) based-films, recently reported in the literature as platforms for tumor cell capture, were developed and, subsequently, functionalized with sulfated chitosan (ChiS) using a layer-by-layer technique. ChiS, when compared to native Chi, presents the unique abilities to confer anti-thrombogenic properties, to reduce protein adsorption, and also to limit calcification. Film physicochemical characterization was carried out using FTIR and XPS for chemical composition assessment, AFM for the surface morphology, and contact angle for hydrophilicity evaluation. The deposition of ChiS monolayer promoted a decrease in both roughness and hydrophilicity of the HA/Chi films. In addition, the appearance of sulfur in the chemical composition of ChiS-functionalized films confirmed the film modification. Biological assay indicated that the incorporation of sulfated groups limited platelet adhesion, mainly because a significant reduction of platelets adhesion to ChiS-functionalized films was observed compared to HA/Chi films. On balance, this work provides a new insight for the development of novel antithrombogenic biomaterials, opening up new possibilities for devising blood-interaction surfaces.
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Quitosano , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Quitosano/química , Ácido Hialurónico/química , Polisacáridos/química , Sulfatos , Propiedades de SuperficieRESUMEN
Bone regeneration and vascularization have presented a clinical challenge for decades. Considering the importance of stem cells, such as mesenchymal stem cells (MSCs), in bone regeneration, endothelial progenitor cells (EPCs) are crucial during bone repair. This paper presented sulfated chitosan (SCS)-based hydrogel scaffolds to accelerate bone tissue regeneration, vascularization enhancement, and improve bone repair. Thus, these scaffolds played a crucial role in the regeneration of blood vessels, with the increased presentation of epithelial progenitors and immune cells in this microenvironment. In vivo experiments showed that the biological impact of SCS was critical for angiogenesis and vascularization, in conjunction with bone morphogenetic protein-2 (BMP-2) and MSCs. Therefore, the BMP-2-/hydrogel system established in this study promoted angiogenesis, stimulated MSC proliferation, and enhanced bone tissue formation. In addition, this paper highlighted the angiogenic role of SCS in creating a micro-environment for effective bone repair and provides insight into the future development of new bone regeneration material.
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Quitosano , Osteogénesis , Regeneración Ósea , Quitosano/farmacología , Hidrogeles/farmacología , Neovascularización Fisiológica , Sulfatos/farmacología , Andamios del TejidoRESUMEN
Development of multifunctional antibacterial agent with long-lasting antibacterial activity and biofilm ablation performance is significant for the effective treatment of bacterial infections. Here, by utilizing the electrostatic interaction between sulfonated chitosan (SCS) and Ag+ and chitosan (CS), and the sodium borohydride reduction method, a versatile antibacterial agent (AgNPs@CS/SCS) capable of generating silver nanoparticles (AgNPs) in-situ and long-acting slow-release Ag+ was developed. AgNPs@CS/SCS has a good physiological stability and can long-acting slow-release of Ag+ due to the pH-dependent Ag+ release behavior of AgNPs. Noteworthy, AgNPs@CS/SCS can exert both excellent short- and long-term antibacterial and biofilm ablation activity. Importantly, it also exhibits superior antibacterial activity in the treatment of implant infections, accompanied by good biocompatibility. Together, this study suggest that AgNPs@CS/CSC is indeed a versatile antibacterial agent, and is expected to provide an effective treatment modality for implant infections in the clinic settings.
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Antibacterianos/farmacología , Materiales Biocompatibles/química , Quitosano/química , Sistemas de Liberación de Medicamentos , Nanopartículas del Metal/química , Nanogeles/química , Plata/química , Biopelículas/crecimiento & desarrollo , Preparaciones de Acción Retardada/química , Escherichia coli/efectos de los fármacos , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Electricidad EstáticaRESUMEN
In this study, we synthesized negatively charged chitosan sulfate and positively charged hydroxypropyltrimethyl ammonium chloride chitosan (HACC), and then prepared chitosan derivatives with positive and negative ions as nanoparticles (NPs) by ovalbumin encapsulation using the polyelectrolyte method. NPs with different substitution sites and molecular weights (MW) were prepared by varying conditions. We then determined the zeta potential average, diameter, encapsulation effect, and their immunostimulatory effects on dendritic cells (DCs). The results showed that chitosan-derivative NPs ranged in size from 153.33 to 320.90 nm; all NPs were positive, with charges ranging from 17.10 to 39.30 mV and the encapsulation rates of 65 %-75 %. Three NPs greatly promoted the expression and secretion of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and interleukin-1ß (IL-1ß) in DC cells: C2,3,6 chitosan sulfate-HACC (C2,3,6-HACC; 200 kDa), C3,6 chitosan sulfate-HACC (C3,6-HACC; 200 kDa) and C6 chitosan sulfate-HACC (C6-HACC; 50 kDa). We also found that 200-kDa C2,3,6-HACC and 50-kDa C6-HACC NPs greatly increased secretion of the major histocompatibility complex-II (MHC-II), CD40, CD80, and CD86, indicating that these NPs promote effective antigen presentation, further increasing immunity effects. Finally, we applied laser confocal photography and determined that NPs entered the cell to promote the regulation of cellular immune activity; this discovery lays a foundation for further research on their mechanism of their action. Therefore, C2,3,6-HACC and C6-HACC NPs have the potential as immunological adjuvants.
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Quitosano/análogos & derivados , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Nanopartículas/química , Compuestos de Amonio Cuaternario/química , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacología , Animales , Quitosano/química , Quitosano/farmacología , Citocinas/inmunología , Humanos , Inmunomodulación/efectos de los fármacosRESUMEN
Emerging evidence suggests that dysfunctional macrophages can cause chronic inflammation and impair tissue regeneration in diabetic wounds. Therefore, improving macrophage behaviors and functions may improve therapeutic outcomes of current treatments in diabetic wounds. Herein, we present a sulfated chitosan (SCS)-doped Collagen type I (Col I/SCS) hydrogel as a candidate for diabetic wound treatments, and assess its efficacy using streptozocin (STZ)-induced diabetic wound model. Results showed that Col I/SCS hydrogel significantly improved wound closure rate, collagen deposition, and revascularization in diabetic wounds. Flow cytometry analysis and immunofluorescent staining analysis showed that the Col I/SCS hydrogel accelerated the resolution of excessive inflammation by reducing the polarization of M1-like macrophages in chronic diabetic wounds. In addition, ELISA analysis revealed that the Col I/SCS hydrogel reduced the production of pro-inflammatory interleukin (IL)-6 and increased the production of anti-inflammatory cytokines including IL-4 and transforming growth factor-beta 1 (TGF-ß1) during wound healing. Moreover, the Col I/SCS hydrogel enhanced the transdifferentiation of macrophages into fibroblasts, which enhanced the formation of collagen and the extracellular matrix (ECM) in wound tissue. We highlight a potential application of manipulating macrophages behaviors in the pathological microenvironment via materials strategy. STATEMENT OF SIGNIFICANCE: Improving the chronic inflammatory microenvironment of diabetic wounds by regulating macrophage behaviors has been of wide concern in recent years. We designed a Col I/SCS hydrogel based on Collagen type I and sulfated chitosan (SCS) without exogenous cells or cytokines, which could significantly improve angiogenesis and resolve chronic inflammation in diabetic wounds, and hence accelerate diabetic wound healing. The Col I/SCS hydrogel could facilitate the polarization of M1-to-M2 macrophages and activate the transdifferentiation of macrophages to fibroblasts. Additionally, the Col I/SCS hydrogel also equilibrated the content of pro-inflammatory and anti-inflammatory cytokines. This strategy may afford a new avenue to improve macrophage functions and accelerate diabetic chronic wound healing.
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Quitosano , Diabetes Mellitus Experimental , Animales , Quitosano/farmacología , Macrófagos , Ratones , Sulfatos , Cicatrización de HeridasRESUMEN
This study aimed to compare the effects of the two type chitosan derivatives, sulfated chitosan (SCS) and phosphorylated chitosan (PCS), coated on poly(d,l-lactide) (PDLLA) membrane via polydopamine, respectively, on vascularization and osteogenesis in vitro. Mouse preosteoblast cells (MC3T3-E1s) and human umbilical vein endothelial cells (HUVECs) were used as co-cultures system. The effects of two type membranes on calcium deposition, alkaline phosphatase (ALP) activity, vascularization related factors nitric oxide (NO) and angiogenic growth factor vascular endothelial growth factor (VEGF) were assessed. The changes of osteogenic and angiogenic related gene, and protein expression were evaluated too. In fact, SCS modified PDLLA membrane had the highest related gene and protein expression than other PDLLA membranes. Our results demonstrated that the SCS maybe a promising matrix for bone regeneration by co-cultures of ECs and OCs than PCS.
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Diferenciación Celular/efectos de los fármacos , Quitosano/farmacología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Membranas Artificiales , Neovascularización Fisiológica/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Poliésteres/farmacología , Animales , Regeneración Ósea/efectos de los fármacos , Células Cultivadas , Técnicas de Cocultivo , Expresión Génica/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Ratones , Neovascularización Fisiológica/genética , Óxido Nítrico/metabolismo , Osteogénesis/genética , Ingeniería de Tejidos/métodos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The vascularization within the scaffold is still a significant challenge in tissue engineering applications. Sulfated chitosan (SCS) as an amazing substance have been used in tissue engineering to stimulate angiogenesis. However, it is not clear whether they have difference in the ability to promote vascularization of SCS with different sulfonic acid group sites. The aim of this study was to evaluate human umbilical vein endothelial cells (HUVECs) viability and differentiation in vitro, affected by three types of sulfated chitosan' i.e. 2-N-6-O-sulfated chitosan (2,6-SCS), 3'6-O-sulfated chitosan (3,6-SCS) and 6-O-sulfated chitosan (6-SCS). The results are showed that all the SCS possesses excellent biological properties to promote HUVECs viability and proliferation. Especially, 2,6-SCS promotes desirable intracellular nitric oxide secretion and capillary tube formation. Meanwhile, 2,6-SCS up-regulate the related gene and protein expression compared with other sulfonic acid group sites SCS and heparin. Therefore, 2,6-SCS is a promising substitute material for angiogenesis and as aqueous formulation can be employed to fabrication functionalization scaffold surface with promoted angiogenesis.
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Quitosano/química , Quitosano/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Sulfatos/química , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Óxido Nítrico/metabolismo , Relación Estructura-ActividadRESUMEN
Bioresorbable polymeric stents have attracted great interest for coronary artery disease because they can provide mechanical support first and then disappear within a desired time period. The conventional manufacturing process is laser cutting, and generally they are fabricated from tubular prototypes produced by injection molding or melt extrusion. The aim of this study is to fabricate and characterize a novel bioresorbable polymeric stent for treatment of coronary artery disease. Polycaprolactone (PCL) is investigated as suitable material for biomedical stents. A rotary 3D printing method is developed to fabricate the polymeric stents. Surface modification of polymeric stent is performed by immobilization of 2-N, 6-O-sulfated chitosan (26SCS). Physical and chemical characterization results showed that the surface microstructure of 3D-pinted PCL stents can be influenced by 26SCS modification, but no significant difference was observed for their mechanical behavior. Biocompatibility assessment results indicated that PCL and S-PCL stents possess good compatibility with blood and cells, and 26SCS modification can enhance cell proliferation. These results suggest that 3D printed PCL stent can be a potential candidate for coronary artery disease by modification of sulfated chitosan (CS).
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Chitosan (CS) and its water-soluble derivatives, hydroxypropyltrimethyl ammonium chloride chitosan (HACC) and sulfated chitosan (SCS), were used as adjuvants of inactivated Newcastle disease (ND) vaccine. First, NDV-loaded and blank CS, HACC/CS and SCS nanoparticles were prepared. The particle sizes were respectively 343.43⯱â¯4.12, 320.03⯱â¯0.84, 156.2⯱â¯9.29â¯nm and the zeta potentials were respectively +19.67⯱â¯0.58, +18.3⯱â¯0.5, -17.8⯱â¯2.65â¯mV under the optimal conditions. Then chickens were immunized with nanoparticles or commercial inactivated oil emulsion vaccine. After immunization, the humoral immunity levels of the chickens were evaluated. The cellular immunity levels were determined by the quantification of cytokines, lymphocyte proliferation assay, the percentages of CD4+ and CD8+ T lymphocytes. Finally, the chickens were challenged with highly virulent virus. The results demonstrated that the humoral immunity levels in NDV-loaded CS and HACC/CS nanoparticles groups were lower than commercial vaccine but the cellular immunity levels are better. Moreover, the prevention effects of NDV-loaded CS and HACC/CS nanoparticles against highly virulent NDV are comparable to commercial vaccine. Our study provides the basis of developing HACC and CS as effective vaccine adjuvants.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Quitosano/análogos & derivados , Nanopartículas/administración & dosificación , Enfermedad de Newcastle/prevención & control , Enfermedades de las Aves de Corral/prevención & control , Compuestos de Amonio Cuaternario/administración & dosificación , Vacunas de Productos Inactivados/administración & dosificación , Vacunas Virales/administración & dosificación , Animales , Pollos , Quitosano/administración & dosificación , Citocinas/inmunología , Inmunidad Humoral , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Ratones , Virus de la Enfermedad de Newcastle/inmunología , Células RAW 264.7 , Vacunación/métodosRESUMEN
Preserving the bioactivity of growth factors (GFs) and mimicking their in vivo supply patterns are challenging in the development of GFs-based bone grafts. In this study, we develop a 2-N, 6-O-sulfated chitosan (26SCS) functionalized dual-modular scaffold composed of mesoporous bioactive glass (MBG) with hierarchical porous structures (module I) and GelMA hydrogel columns (module II) in situ fixed in hollowed channels of the module I, which is capable of realizing differentiated delivery modes for osteogenic rhBMP-2 and angiogenic VEGF. A combinational release profile consisting of a high concentration of VEGF initially followed by a decreasing concentration over time, and a slower/sustainable release of rhBMP-2 is realized by immobilizing rhBMP-2 in module I and embedding VEGF in module II. Systematic in vitro and in vivo studies prove that the two coupled processes of osteogenesis and angiogenesis are well-orchestrated and both enhanced ascribed to the specific GFs delivery modes and 26SCS decoration. 26SCS not only enhances the GFs' bioactivity but also decreases antagonism effects of noggin. This study highlights the importance of differentiating the delivery pattern of different GFs and likely sheds light on the future design of growth factor-based bone grafts.