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Single-atom catalysts, characterized by transition metal-(N/O)4 units on nanocarbon (M-(N/O)4-C), have emerged as efficient performers in water electrolysis. However, there are few guiding principles for accurately controlling the ligand fields of single atoms to further stimulate the catalyst activities. Herein, using the Ni-(N/O)4-C unit as a model, we develop a further modification of the P anion on the outer shells to modulate the morphology of the ligand. The catalyst thus prepared possesses high activity and excellent long-term durability, surpassing commercial Pt/C, RuO2, and currently reported single-atom catalysts. Notably, mechanistic studies demonstrated that the pseudocapacitive feature of multiscale anion-hybrid nanocarbon is considerable at accumulating enough positive charge [Q], contributing to the high oxygen evolution reaction (OER) order (ß) through the rate formula. DFT calculations also indicate that the catalytic activity is decided by the suitable barrier energy of the intermediates due to charge accumulation. This work reveals the activity origin of single atoms on multihybrid nanocarbon, providing a clear experiential formula for designing the electronic configuration of single-atom catalysts to boost electrocatalytic performance.
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Accumulation of reactive oxygen species (ROS) in periodontitis exacerbates the destruction of alveolar bone. Therefore, scavenging ROS to reshape the periodontal microenvironment, alleviate the inflammatory response and promote endogenous stem cell osteogenic differentiation may be an effective strategy for treating bone resorption in periodontitis. In this study, sericin-hydroxyapatite nanoparticles (Se-nHA NPs) are synthesized using a biomimetic mineralization method. Se-nHA NPs and proanthocyanidins (PC) are then encapsulated in sericin/sodium alginate (Se/SA) using an electrostatic injection technique to prepare Se-nHA/PC microspheres. Microspheres are effective in scavenging ROS, inhibiting the polarization of macrophages toward the M1 type, and inducing the polarization of macrophages toward the M2 type. In normal or macrophage-conditioned media, the Se-nHA/PC microspheres effectively promoted the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Furthermore, the Se-nHA/PC microspheres demonstrated anti-inflammatory effects in a periodontitis rat model by scavenging ROS and suppressing pro-inflammatory cytokines. The Se-nHA/PC microspheres are also distinguished by their capacity to decrease alveolar bone loss, reduce osteoclast activity, and boost osteogenic factor expression. Therefore, the biomimetic Se-nHA/PC composite microspheres have efficient ROS-scavenging, anti-inflammatory, and osteogenic abilities and can be used as a multifunctional filling material for inflammatory periodontal tissue regeneration.
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Periodontite , Proantocianidinas , Sericinas , Humanos , Animais , Ratos , Osteogênese , Biomimética , Microesferas , Espécies Reativas de Oxigênio , Regeneração Óssea , Periodontite/terapia , Durapatita , Anti-InflamatóriosRESUMO
It has been shown that exposure to hexavalent Chromium, Cr (â ¥), via nasal cavity can have neurotoxicological effects and induces behavioral impairment due to the fact that blood brain barrier (BBB) does not cover olfactory bulb. But whether Cr (â ¥) can cross the BBB and have a toxicological effects in central nervous system (CNS) remains unclear. Therefore, we investigated the effects of Cr (â ¥) on mice treated with different concentrations and exposure time (14 days and 28 days) of Cr (â ¥) via intraperitoneal injection. Results revealed that Cr accumulated in hypothalamus (HY) in a timely dependent manner. Much more severer neuropathologies was observed in the group of mice exposed to Cr (â ¥) for 28 days than that for 14 days. Gliosis, neuronal morphological abnormalities, synaptic degeneration, BBB disruption and neuronal number loss were observed in HY. In terms of mechanism, the Nrf2 related antioxidant stress signaling dysfunction and activated NF-κB related inflammatory pathway were observed in HY of Cr (â ¥) intoxication mice. And these neuropathologies and signaling defects appeared in a timely dependent manner. Taking together, we proved that Cr (â ¥) can enter HY due to weaker BBB in HY and HY is the most vulnerable CNS region to Cr (â ¥) exposure. The concentration of Cr in HY increased along with time. The accumulated Cr in HY can cause BBB disruption, neuronal morphological abnormalities, synaptic degeneration and gliosis through Nrf2 and NF-κB signaling pathway. This finding improves our understanding of the neurological dysfunctions observed in individuals who have occupational exposure to Cr (â ¥), and provided potential therapeutic targets to treat neurotoxicological pathologies induced by Cr (â ¥).
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Barreira Hematoencefálica , NF-kappa B , Camundongos , Animais , Barreira Hematoencefálica/metabolismo , NF-kappa B/metabolismo , Cromo/toxicidade , Gliose , Fator 2 Relacionado a NF-E2/metabolismo , Modelos Animais de Doenças , Hipotálamo/metabolismoRESUMO
Bacterial infections can significantly impede wound healing and pose a serious threat to the patient's life. The excessive use of antibiotics to combat bacterial infections has led to the emergence of multi-drug-resistant bacteria. Therefore, there is a pressing need for alternative approaches, such as photothermal therapy (PTT), to address this issue. In this study, for the first time, CuS NPs with photothermal properties were synthesized using sericin as a biological template, named CuS@Ser NPs. This method is simple, green, and does not produce toxic and harmful by-products. These nanoparticles were incorporated into a mixture (XK) of xanthan gum and konjac glucomannan (KGM) to obtain XK/CuS NPs composite hydrogel, which could overcome the limitations of current wound dressings. The composite hydrogel exhibited excellent mechanical flexibility, photothermal response, and biocompatibility. It also demonstrated potent antibacterial properties against both Gram-positive and negative bacteria via antibacterial experiments and accelerated wound healing in animal models. Additionally, it is proved that the hydrogel promoted tissue regeneration by stimulating collagen deposition, angiogenesis, and reducing inflammation. In summary, the XK/CuS NPs composite hydrogel presents a promising alternative for the clinical management of infected wounds, offering a new approach to promote infected wound healing.
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Infecções Bacterianas , Hidrogéis , Animais , Hidrogéis/farmacologia , Cicatrização , Antibacterianos/farmacologia , ColágenoRESUMO
Currently, adhesive hydrogels have shown promising effect in chronic diabetic wound repair. However, there are issues and challenges in treating diabetic wounds due to inadequate wet adhesion, unable to fill irregular and deep wounds, and oxidative stress. Herein, a mussel-inspired naturally hydrogel dressing with rapid shape adaptability, wet adhesion and antioxidant abilities for irregular, deep and frequently movement diabetic wounds repair was constructed by comprising catechol modified carboxymethyl cellulose (CMC-DA) and tannic acid. Benefiting from the reversible hydrogen bonding, the resulting hydrogels exhibited injectability, remarkable self-healing ability, rapid shape adaptability and strong tissue adhesion (45.9 kPa), thereby contributing to self-adaptive irregular-shaped wounds or moving joint parts. Especially, the adhesion strength of the hydrogel on wet tissue still remained at 14.9 kPa. Besides, the hydrogels could be easily detached from the skin by ice-cooling that avoided secondary damage caused by dressing change. Remarkably, the hydrogels possessed excellent antioxidant, satisfactory biocompatibility, efficient hemostasis and antibacterial properties. The in vivo evaluation further demonstrated that the hydrogel possessed considerable wound-healing promotion effect by regulating diabetic microenvironment, attributed to that the hydrogel could significantly reduce inflammatory response, alleviate oxidative stress and regulate neovascularization. Overall, this biosafe adhesive hydrogel had great potentials for diabetic wound management.
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Antioxidantes , Diabetes Mellitus , Polifenóis , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Hidrogéis/farmacologia , Carboximetilcelulose Sódica/farmacologia , Estresse Oxidativo , AntibacterianosRESUMO
BACKGROUND: Systemic and pulmonary coagulopathy and inflammation are important characteristics of transfusion-related acute lung injury (TRALI). Whether microparticles that accumulate in transfused red blood cell concentrates (RBCs) have proinflammatory and procoagulant potential and contribute to adverse reactions of RBC transfusions is unclear. AIM: To investigate the ability of microparticles in stored RBCs to promote thrombin generation and induce human pulmonary microvascular endothelial cell (HMVEC) activation and damage. METHODS: The number and size of microparticles were determined by flow cytometric and nanoparticle tracking analyses, respectively. Thrombin generation and the intrinsic coagulation pathway were assayed by a calibrated automated thrombogram and by measuring activated partial thromboplastin time (aPTT), respectively. The expression of ICAM-1 and the release of cytokines by endothelial cells were detected by flow cytometric analyses. HMVEC damage was assessed by incubating lipopolysaccharide-activated endothelial cells with MP-primed polymorphonuclear neutrophils (PMNs). RESULTS: The size of the microparticles in the RBC supernatant was approximately 100-300 nm. Microparticles promoted thrombin generation in a dose-dependent manner and the aPTT was shortened. Depleting microparticles from the supernatant of RBCs stored for 35 days by either filtration or centrifugation significantly decreased the promotion of thrombin generation. The expression of ICAM-1 on HMVECs was increased significantly by incubation with isolated microparticles. Furthermore, microparticles induced the release of interleukin-6 (IL-6) and interleukin-8 (IL-8) from HMVECs. Microparticles induced lipopolysaccharide-activated HMVEC damage by priming PMNs, but this effect was prevented by inhibiting the PMNs respiratory burst with apocynin. CONCLUSION: Microparticles in stored RBCs promote thrombin generation, HMVEC activation and damage which may be involved in TRALI development.
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Bone defects caused by trauma, tumor resection, or developmental abnormalities are important issues in clinical practice. The vigorous development of tissue engineering technology provides new ideas and directions for regenerating bone defects. Hydroxyapatite (HAp), a bioactive ceramic, is extensively used in bone tissue engineering because of its excellent osteoinductive performance. However, its application is challenged by its single function and conventional environment-unfriendly synthesis methods. In this study, we successfully "green" synthesized sr-silk fibroin co-assembly hydroxyapatite nanoparticles (Sr-SF-HA) using silk fibroin (SF) as a biomineralized template, thus enabling it to have angiogenic activity and achieving the combination of organic and inorganic substances. Then, the rough composite microspheres loaded with Sr-SF-HA (CS/Sr-SF-HA) through electrostatic spraying technology and freeze-drying method were prepared. The CCK-8 test and live/dead cell staining showed excellent biocompatibility of CS/Sr-SF-HA. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS), immunofluorescence, western blotting, and qRT-PCR test showed that CS/Sr-SF-HA activated the expression of related genes and proteins, thus inducing the osteogenic differentiation of rBMSCs. Moreover, tube formation experiments, scratch experiments, immunofluorescence, and qRT-PCR detection indicated that CS/Sr-SF-HA have good angiogenic activity. Furthermore, in vivo studies showed that the CS/Sr-SF-HA possesses excellent biocompatibility, vascular activity, as well as ectopic osteogenic ability in the subcutaneous pocket of rats. This study indicates that the construction of CS/Sr-SF-HA with angiogenic and osteogenic properties has great potential for bone tissue engineering.
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BACKGROUND: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). METHODS: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). RESULTS: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1ß, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. CONCLUSION: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.
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Apoptose , Modelos Animais de Doenças , Eletroacupuntura , Interleucina 22 , Interleucinas , Degeneração do Disco Intervertebral , Janus Quinase 2 , Núcleo Pulposo , Ratos Sprague-Dawley , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Degeneração do Disco Intervertebral/terapia , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/genética , Núcleo Pulposo/metabolismo , Núcleo Pulposo/citologia , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Ratos , Interleucinas/metabolismo , Interleucinas/genética , Masculino , Humanos , Vértebras CervicaisRESUMO
The heterogeneity and mechanisms for the generation of CD4 memory T (CD4 Tm) cells remain elusive. Distinct subsets of dendritic cells (DCs) have been found to regulate a distinct T-helper (Th)-cell subset differentiation by influencing cytokine cues around CD4 T cells; however, whether and how the regulatory DC subset can regulate Tm-cell differentiation remains unknown. Further, there is no ideal in vitro experimental system with which to mimic the 3 phases of the CD4 T-cell immune response (expansion, contraction, memory generation) and/or to culture CD4 Tm cells for more than a month. By analyzing CD4 T cells programmed by long-term coculture with regulatory DCs, we identified a population of long-lived CD4 T cells with a CD44(hi)CD62L(-)CCR7(-) effector memory phenotype and rapid, preferential secretion of the Th2 cytokines interleukin-4 (IL-4), IL-5, IL-10, and IL-13 after antigenic stimulation. These regulatory DC-programmed Tm cells suppress CD4 T-cell activation and proliferation in vitro via IL-10 and inhibit the delayed-type hypersensitivity response once infused in vivo. We also identify their natural counterpart, which is up-regulated by regulatory DC transfusion and negatively regulates the recall response in vivo. Different from interferon-γ-producing conventional Tm cells, these IL-4-producing CD4 Tm cells act as alternative Tm cells with a regulatory function, suggesting a new way of negative immune regulation by memory T cells.
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Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/fisiologia , Células Dendríticas/fisiologia , Tolerância Imunológica/imunologia , Memória Imunológica/imunologia , Interleucina-4/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/imunologia , Proliferação de Células , Células Cultivadas , Células Dendríticas/imunologia , Citometria de Fluxo , Memória Imunológica/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/fisiologiaRESUMO
Trade-off of high-strength and dynamic crosslinking of hydrogels remains an enormous challenge. Motivated by the self-healing property of biological tissues, the strategy of combining multiple dynamic bond mechanisms and a polysaccharide network is proposed to fabricate biomimetic hydrogels with sufficient mechanical strength, injectability, biodegradability, and self-healing property for bone reconstruction engineering. Stable acylhydrazone bonds endowed hydrogels with robust mechanical strength (>10 kPa). The integration of dynamic imine bonds and acylhydrazone bonds optimized the reversible characteristic to protect the cell during the injection and mimicked ECM microenvironment for cell differentiation as well as rapid adapting bone defect area. Furthermore, due to the slow enzymatic hydrolysis kinetics of chitosan and the self-healing properties of resulting networks, hydrogels exhibited a satisfactory biodegradation period (>8 weeks) that highly matches with bone regeneration. Additionally, rBMSC-laden hydrogels exhibited splendid osteogenic induction and bone reconstruction without prefabrication scaffolds and incubation, demonstrating tremendous potential for clinical application. This work proposes an efficient strategy for the construction of a low-cost multifunctional hydrogel, making polysaccharide-based hydrogels as the optimal carrier for enabling cellular functions in bone repair.
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Quitosana , Quitosana/química , Hidrogéis/farmacologia , Hidrogéis/química , Quitina , Polissacarídeos , Regeneração ÓsseaRESUMO
To promote the functional applications of lotus root polysaccharides (LRPs), the effects of noncovalent polyphenol binding on their physicochemical properties, as well as antioxidant and immunomodulatory activities, were investigated. Ferulic acid (FA) and chlorogenic acid (CHA) were spontaneously bound to the LRP to prepare the complexes LRP-FA1, LRP-FA2, LRP-FA3, LRP-CHA1, LRP-CHA2 and LRP-CHA3, and their mass ratios of polyphenol to LRP were, respectively, 121.57, 61.18, 34.79, 2359.58, 1276.71 and 545.08 mg/g. Using the physical mixture of the LRP and polyphenols as a control, the noncovalent interaction between them in the complexes was confirmed by ultraviolet and Fourier-transform infrared spectroscopy. The interaction increased their average molecular weights by 1.11~2.27 times compared to the LRP. The polyphenols enhanced the antioxidant capacity and macrophage-stimulating activity of the LRP depending on their binding amount. Particularly, the DPPH radical scavenging activity and FRAP antioxidant ability were positively related to the FA binding amount but negatively related to the CHA binding amount. The NO production of the macrophages stimulated by the LRP was inhibited by the co-incubation with free polyphenols; however, the inhibition was eliminated by the noncovalent binding. The complexes could stimulate the NO production and tumor necrosis factor-α secretion more effectively than the LRP. The noncovalent binding of polyphenols may be an innovative strategy for the structural and functional modification of natural polysaccharides.
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The development of the effective 3D printing strategy for diverse functional monomers is still challenging. Moreover, the conventional 3D printing hydrogels are usually soft and fragile due to the lack of an energy dissipation mechanism. Herein, a microsphere mediating ink preparation strategy is developed to provide tailored rheological behavior for various monomer direct ink writings. The chitosan microspheres are used as an exemplary material due to their tunable swelling ratio under the acid-drived electrostatic repulsion of the protonated amino groups. The rheological behaviors of the swollen chitosan microsphere (SCM) are independent on the monomer types, and various functional secondary polymers could be carried at a wide loading ratio by the acid driving. The SCM reinforces the hydrogel as the sacrificial bonds. With the adjustable composition, the 3D printing hydrogel mechanical properties are tunable in wide windows: strength (0.4-1.01 MPa), dissipated energy (0.11-3.25 MJ m-3), and elongation at break (47-626%). With the excellent printing and mechanical properties, the SCM inks enable multi-functional integration for soft device production, such as 4D printing robots and wearable strain sensors. We anticipate that this microsphere mediating 3D printing strategy can inspire new possibilities for the design of the robust hydrogels with a broad range of functionalities and mechanical performances.
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Constructing natural polymers such as cellulose, chitin, and chitosan into hydrogels with excellent stretchability and self-healing properties can greatly expand their applications but remains very challenging. Generally, the polysaccharide-based hydrogels have suffered from the trade-off between stiffness of the polysaccharide and stretchability due to the inherent nature. Thus, polysaccharide-based hydrogels (polysaccharides act as the matrix) with self-healing properties and excellent stretchability are scarcely reported. Here, a solvent-assisted strategy was developed to construct MXene-mediated cellulose conductive hydrogels with excellent stretchability (â¼5300%) and self-healability. MXene (an emerging two-dimensional nanomaterial) was introduced as emerging noncovalent cross-linking sites between the solvated cellulose chains in a benzyltrimethylammonium hydroxide aqueous solution. The electrostatic interaction between the cellulose chains and terminal functional groups (O, OH, F) of MXene led to cross-linking of the cellulose chains by MXene to form a hydrogel. Due to the excellent properties of the cellulose-MXene conductive hydrogel, the work not only enabled their strong potential in both fields of electronic skins and energy storage but provided fresh ideas for some other stubborn polymers such as chitin to prepare hydrogels with excellent properties.
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Systemic sclerosis (SSc, scleroderma), is an autoimmune rheumatic disease characterized by fibrosis of the skin and internal organs, and vasculopathy. Preventing fibrosis by targeting aberrant immune cells that drive extracellular matrix (ECM) over-deposition is a promising therapeutic strategy for SSc. Previous research suggests that M2 macrophages play an essential part in the fibrotic process of SSc. Targeted modulation of molecules that influence M2 macrophage polarization, or M2 macrophages, may hinder the progression of fibrosis. Here, in an effort to offer fresh perspectives on the management of scleroderma and fibrotic diseases, we review the molecular mechanisms underlying the regulation of M2 macrophage polarization in SSc-related organ fibrosis, potential inhibitors targeting M2 macrophages, and the mechanisms by which M2 macrophages participate in fibrosis.
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Improving the dispersed stability of selenium nanoparticles (SeNPs) is the key to its application. In this study, yeast glucan with different degrees of amination (BNs) were used as stabilizers and capping agent to prepare dispersed SeNPs. The size, storage stability, and morphology of BNs/SeNPs were characterized. Results show that BNs/SeNPs presented positive potential and spherical morphologies with average particle size about 100-300 nm and kept stable at room temperature for a long time. The CCK-8 assay showed that BNs/SeNPs had significantly lower toxicity to RAW264.7 cells than SeNPs. Moreover, BNs/SeNPs could inhibit the generation of NO, IL-1ß and IL-6 effectively in RAW 264.7 macrophages induced by LPS, and down-regulate the mRNA transcription of iNOS, IL-1ß, IL-6 and chemokines (CCL2 and CCL5), indicating that BNs/SeNPs had good anti-inflammatory activity. Therefore, aminated yeast glucan could improve the stability and bioactivity of SeNPs simultaneously, which is a promising stabilizer for SeNPs.
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Nanopartículas , Selênio , Selênio/farmacologia , Glucanos/farmacologia , Saccharomyces cerevisiae , Interleucina-6 , Anti-Inflamatórios/farmacologiaRESUMO
The development of wound dressings with hemostatic and antibacterial properties has attracted great attention. In this study, we prepared a multi-functional natural substance sponge (CMC/Ser-Ag/HNT) composed of carboxymethyl chitosan (CMC), sericin-silver nanoparticle (Ser-Ag), and halloysite (HNT). CMC/Ser-Ag/HNT sponge was demonstrated to bear desired hygroscopicity, porosity, compressive strength and compressive stability, cytocompatibility, and hemocompatibility. The mechanical properties (compressive strength of 100 kPa) and hemostatic capacity (hemostasis time of 15 ± 3 s in the liver injury model and 12 ± 3 s in the caudal injury model) were enhanced by introducing HNT into the CMC sponge. Ser-Ag was synthesized in situ via the redox nature of tyrosine residues in sericin in a "one-step, green" way to enhance the antibacterial activity of the hybrid sponge against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In addition, the rat full-thickness skin defect model experiments demonstrated that the CMC/Ser-Ag/HNT4 sponge significantly promoted epithelialization and collagen formation. Immunofluorescence staining assays revealed that the composite sponge reduced inflammation by downregulating the expression of IL-6 and enhanced angiogenesis by upregulating VEGF expression. All the findings demonstrated the great potential of CMC/Ser-Ag/HNT sponge as versatile clinical wound dressing, especially for hemorrhagic and infected wounds.
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Quitosana , Hemostáticos , Nanopartículas Metálicas , Sericinas , Ratos , Animais , Quitosana/farmacologia , Quitosana/química , Hemostáticos/farmacologia , Sericinas/farmacologia , Sericinas/química , Argila , Nanopartículas Metálicas/química , Staphylococcus aureus , Escherichia coli , Prata/química , Cicatrização , Bandagens , Hemostasia , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
An ideal wound dressing should have excellent antimicrobial properties and provide a suitable microenvironment for regenerating damaged skin tissue. In this study, we utilized sericin to biosynthesize silver nanoparticles in situ and introduced curcumin to obtain Sericin-AgNPs/Curcumin (Se-Ag/Cur) antimicrobial agent. The hybrid antimicrobial agent was then encapsulated in a physically double cross-linking 3D structure network (Sodium alginate-Chitosan, SC) to obtain the SC/Se-Ag/Cur composite sponge. The 3D structural networks were constructed through electrostatic interactions between sodium alginate and chitosan and ionic interactions between sodium alginate and calcium ions. The prepared composite sponges have excellent hygroscopicity (contact angle 51.3° ± 5.6°), moisture retention ability, porosity (67.32 % ± 3.37 %), and mechanical properties (>0.7 MPa) and exhibit good antibacterial ability against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). In addition, in vivo experiments have shown that the composite sponge promotes epithelial regeneration and collagen deposition in wounds infected with S. aureus or P. aeruginosa. Tissue immunofluorescence staining analysis confirmed that the SC/Se-Ag/Cur complex sponge stimulated upregulated expression of CD31 to promote angiogenesis while downregulating TNF-α expression to reduce inflammation. These advantages make it an ideal candidate for infectious wound repair materials, providing an effective repair strategy for clinical skin trauma infections.
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Anti-Infecciosos , Quitosana , Curcumina , Nanopartículas Metálicas , Sericinas , Antibacterianos/química , Quitosana/química , Alginatos/química , Porosidade , Cicatrização , Nanopartículas Metálicas/química , Staphylococcus aureus , Prata/químicaRESUMO
Tumor local chemotherapy employing injectable hydrogel reservoirs is a promising platform to achieve precise drug administration. However, balanced injectability, pH-responsiveness and long-term hydrolysis resistance of self-healing hydrogels remain appealing challenges. Herein, a modular preassembly strategy combining host-guest interactions with dynamic acylhydrazone bonds, was exploited to fabricate injectable cellulose-based hydrogels (CAAs) dressed with self-healing properties, pH-responsiveness and hydrolytic degradation resistance. Attributed to the host-guest interaction between ß-cyclodextrin (CD) and 1-adamantane (AD), the hydrogels exhibited injectability, self-healing properties (healing efficiency of 97.5%) and rapid recovery (< 10 min) without external stimuli in physiological environment. Moreover, the hydrogels equipped with dynamic acylhydrazone linkages underwent slow hydrolytic degradation (> 30 days) and pH-responsive behavior, endowing the hydrogels with precise spatiotemporal drug release administration. The in vivo application of CAA as a carrier was studied using doxorubicin (DOX) model drug, and the results shows that using CAA as DOX carrier not only greatly enhances the anti-tumor efficacy of DOX, but also reduced the side effects of DOX. STATEMENT OF SIGNIFICANCE: With the preassemble approach combining host-guest interactions with dynamic acylhydrazone bonds, this work demonstrated a multi-functional self-healing hydrogel as drug carrier developed by using natural polysaccharides, which offers a new avenue for the high-value utilization of biomass. The strategy demonstrated in the present work may also supply a pathway for the preparation and regulation of hydrogels as intelligent biomedicine materials.
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Hidrogéis , Neoplasias , Celulose/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Humanos , Hidrogéis/química , Neoplasias/tratamento farmacológicoRESUMO
To meet the rising demand of injectable hydrogels with self-healing, robustness and biocompatibility for biomedical engineering, the reversible ketoester-type acylhydrazone linkages was used for the fabrication of novel cellulose-based hydrogel. The ketoester-type acylhydrazone bond exchanged rapidly, endowing the hydrogels with highly efficient self-healing performance without any external stimuli under physiological environment, which was hardly achieved with the widely used arylhydrozone bond. The dynamic hydrogels exhibited tunable mechanical property, pH responsiveness, injectability and biocompatibility, demonstrating immense applications prospect for various biomedicines, such as drug and cell delivery. The pH-responsive controlled release of model drug doxorubicin (DOX) loaded in the hydrogel was demonstrated. In addition, benefitting from the excellent biocompatibility and the reversible ketoester-type acylhydrazone bonds, cells were encapsulated in the hydrogels as 3D carrier. The covalent adaptable network intensified injectability of cell-laden hydrogels and improved the long-lasting viability for cell culture, showing great potential in the biomedical field.
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Celulose/química , Sistemas de Liberação de Medicamentos/métodos , Hidrazonas/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Técnicas de Cultura de Células , Técnicas de Cultura de Células em Três Dimensões/métodos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Injeções/métodos , CamundongosRESUMO
To meet the demands of various therapeutic tasks, injectable hydrogels with tunable mechanical properties and degradability are highly desired. Herein, we developed an injectable chitin hydrogel system with well-manipulated mechanical properties and degradability through dynamic acylhydrazone crosslinking catalyzed by 4-amino-DL-phenylalanine (Phe-NH2). The mechanical properties and degradability of the hydrogels could be easily adjusted by varying the solid content, while their gelation time could be maintained at a constant level (â¼130 s) by altering Phe-NH2 content, thereby ensuring the good injectability of hydrogels. Moreover, the chitin hydrogels showed excellent self-healing capacity with a healing efficiency up to 95 %. Owing to their superior biocompatibility and biodegradability, the chitin hydrogels could support the proliferation and multi-potent differentiations of rat bone marrow-derived stem cells, serving as a beneficial 3D scaffold for stem cell encapsulation and delivery. This work provides a promising injectable delivery vehicle of therapeutic drugs or cells for tissue regenerative medicine.