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Background: Gu-ben-hua-shi (AESS) formula is a clinical experienced prescription from Guangdong Hospital of Traditional Chinese Medicine (TCM), which is used to treat atopic dermatitis (AD). Our previous work has shown that AESS has therapeutic effect on AD by regulating yes-associated protein (YAP). AESS formula has multi-component and multi-target characteristic, and need to be analyzed by systematic chemical profiling and network pharmacology technology, as well as verification of key signaling pathways. Therefore, this study aimed at investigating the efficacy and effect of AESS formula in the treatment of AD and its effect on NLRP3 signaling pathway. Methods: The components of AESS formula were analyzed and identified by ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC- MS/MS), and the potential mechanism of AESS formula in the treatment of AD was predicted by network pharmacology approach, with detected main components, and the potential components targeted NOD-like receptor thermal protein domain associated protein (NLRP3) signaling pathway [Direct binding with NLRP3, apoptosis-associated speck-like protein (ASC) and Caspase-1] were assessed using molecular docking. AD-like symptoms were constructed by DNCB induced BALB/c mice. The effect of AESS formula on dorsal skin structure in AD-like mice was observed using H&E staining. Furthermore, the western blotting experiment explored the expression of the NLRP3 pathway protein. Results: By UHPLC-MS/MS analysis, 91 compounds were detected in AESS formula, and 76 of them were identified, while by network pharmacological analysis, 1500 component targets were obtained, and 257 of them were obtained by intersection with eczema targets. Then one of the key pathways, nucleotide-binding oligomerization domain (NOD)-like signaling pathway was obtained by KEGG enrichment analysis. Molecular docking results showed 24 main components could effectively combine with ASC and Caspase-1 (≤-7 kcal/mol). The animal experiment results further showed that AESS formula alleviates symptoms in AD-like mice. ELISA kit results showed that the expression of IL-1ß and IL-18 in serum was inhibited after AESS treatment. Additionally, western blotting analysis showed that the expressions of ASC, Caspase-1 and NLRP3 protein expression in the skin tissue of mice were down-regulated after AESS treatment. The experimental results show that AESS formula inhibited the expression of NLRP3 signaling pathway for the treatment of AD. Conclusions: AESS formula can improve AD symptoms in mice by inhibiting the activation of NLRP3 inflammasome and the expression of the related downstream inflammatory cytokines.
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Rupture of tendons and ligaments (T/L) is a major clinical challenge due to T/L possess anisotropic mechanical properties and hierarchical structures. Here, to imitate these characteristics, an approach is presented by fabricating hybrid nanofibrous composites. First, hybrid fiber-reinforced yarns are fabricated via successively electrospinning poly(L-lactide-co-ε-caprolactone) (PLCL) and gelatin (Ge) nanofibers onto polyethylene terephthalate (PET) fibers to improve biodurability and biocompatibility. Then, by comparing different manufacturing methods, the knitted structure succeeds in simulating anisotropic mechanical properties, even being stronger than natural ligaments, and possessing comfort compliance superior to clinically used ligament advanced reinforcement system (LARS) ligament. Moreover, after inoculation with tendon-derived stem cells and transplantation in vivo, hybrid nanofibrous composites are integrated with native tendons to guide surrounding tissue ingrowth due to the highly interconnected and porous structure. The knitted hybrid nanofibrous composites are also ligamentized and remodeled in vivo to promote tendon regeneration. Specifically, after the use of optimized anisotropic hybrid nanofibrous composites to repair tendon, the deposition of tendon-associated extracellular matrix proteins is more significant. Thus, this study indicates a strategy of manufacturing anisotropic hybrid nanofibrous composites with superior mechanical properties and good histocompatibility for clinical reconstruction.
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Nanofibras , Ligamentos , Nanofibras/química , Poliésteres/química , Regeneração , Tendões , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
The study aimed to evaluate the safety and function of poly(lactic-acid-co-ε-caprolactone) (PLCL)/fibrinogen nanofibers (P/F-Ns), and provide theoretical basis for the clinical application. The surface morphology, mechanical properties, the hydrophilicity and the fibrinogen content of P/F-Ns were tested by scanning electron microscope, the material testing machine, the contact angle meter and the microplate reader, respectively. The cell adhesion, proliferation and ligament remodeling genes expression of Hig-82 cells on P/F-Ns were conducted through cell counting kit-8 (CCK-8) and real-time quantitative PCR analyses, respectively. The results showed that with the increase of the fibrinogen content, the pore sizes and hydrophilicity of three P/F-Ns increased, but the mechanical properties decreased. Cell adhesion and proliferation tests showed that P/F-N-2 held the best ability to promote cell adhesion and proliferation. The ligament remodeling genes expressions of Hig-82 cells on P/F-N-1, P/F-N-2 and P/F-N-3 were all up-regulated compared to P/F-N-0 on days 3 and 7. All the three P/F-Ns containing fibrinogen (P/F-N-1, P/F-N-2 and P/F-N-3) had better biocompatibility compared to P/F-N-0, and could be efficiently applied to the reconstruction of anterior cruciate ligament.
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Reconstrução do Ligamento Cruzado Anterior , Nanofibras , Adesão Celular , Fibrinogênio , Teste de MateriaisRESUMO
Psoriasis is a chronic, inflammatory skin disease with a high incidence and recurrence; however, its exact pathogenesis and aetiology remain unclear. This study aimed to analyse the effect of the upstream negative regulator RAS-association domain family 1A (RASSF1A) on Yes-associated protein (YAP) in psoriasis. Skin lesions of 22 patients with psoriasis and 19 healthy controls were used. Human epidermal keratinocytes stimulated by M5 (IL-1α, IL-17, IL-22, TNF-α and oncostatin M) were used to establish a psoriatic cell model. BALB/c mice treated with topical imiquimod were used to establish a psoriatic mouse model. As the methylation level of RASSF1A increased, its expression in psoriatic patients and mice model decreased. Addition of the methylation inhibitor 5-Aza-CdR or RASSF1A-overexpressing lentivirus vector increased RASSF1A and reduced YAP expression; meanwhile improved skin lesions, reduced cell proliferation, induced cell cycle arrest in the G0/G1 phase, increased apoptosis, reduced inflammatory cytokines and activities of ERK, STAT3 and NF-κB signalling pathways. The results indicated that RASSF1A could play a role in the treatment of psoriasis by inhibiting YAP expression. Based on these findings, targeted drugs that can inhibit the methylation or increase the expression of RASSF1A may be useful for treating psoriasis.
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Biomarcadores/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Regulação da Expressão Gênica , Psoríase/patologia , Pele/patologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Apoptose , Estudos de Casos e Controles , Proteínas de Ciclo Celular/genética , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Prognóstico , Psoríase/genética , Psoríase/metabolismo , Transdução de Sinais , Pele/metabolismo , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: Most of the natural extracellular matrix (ECM) is a three-dimensional (3D) network structure of micro/nanofibers for cell adhesion and growth of 3D. Electrospun fibers distinctive mimicked 2D ECM, however, it is impossible to simulate 3D ECM because of longitudinal collapse of continuous micro/nanofibers. Herein, 3D electrospun micro/nano-fibrous sponge was fabricated via electrospinning, homogenization, shaping and thermal crosslinking for 3D tissue regeneration of cells and vascular. RESULTS: Fibrous sponge exhibited high porosity, water absorption and compression resilience and no chemical crosslinked agent was used in preparation process. In vitro studies showed that the 3D short fiber sponge provided an oxygen-rich environment for cell growth, which was conducive to the 3D proliferation and growth of HUVECs, stimulated the expression of VEGF, and well promoted the vascularization of HUVECs. In vivo studies showed that the 3D short fiber sponges had a good 3D adhesion to the chronic wound of diabetes in rats. Furthermore, 3D short fibrous sponges were better than 2D micro/nanofiber membranes in promoting the repair of diabetic full-thickness skin defects including wound healing, hair follicle regeneration, angiogenesis, collagen secretion. CONCLUSION: Therefore, electrospun short fibrous sponges are special candidates for mimicking the 3D ECM and promoting 3D regeneration of tissue.
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Matriz Extracelular/química , Nanofibras/química , Poríferos , Animais , Materiais Biocompatíveis/química , Adesão Celular , Colágeno , Elasticidade , Masculino , Porosidade , Ratos , Ratos Sprague-Dawley , Pele , Engenharia Tecidual/métodos , CicatrizaçãoRESUMO
BACKGROUND: Scalp mycosis is often caused by dermatophytes and was so called tinea capitis. There is no published report caused by Aspergillus protuberus. We report a rare case of kerion-type scalp mycosis caused by A. protuberus. CASE PRESENTATION: A 5-year-old girl developed pyogenic mass with pain for 8 days and got a fever for 2 days prior to admission. Surgical incision and drainage of the mass, intravenous cefuroxime and metronidazole in the local hospital aggravated the skin lesions. Species identification was performed by observation of morphologic and biochemical characteristicsand sequencing of the internal transcribed spacer (ITS) and ß-tubulin (BT2). Treatment with oral and topical antifungal agents was effective with no relapse during the six months of clinical follow-up. CONCLUSIONS: Aspergillusis a opportunistic pathogenic fungus and its infection occurs mostly in patients with underlying conditions and immunocompromised statuses. So far no report of kerion-type scalp infection has been reported. The first case of kerion-type scalp mycosis caused by A. protuberus was described to highlight the importance of mycological examination that helps to recognize rare pathogenic fungi. Any boggy lesion with hair loss over the scalp and non-responsive to antibiotics should be suspected as resulting from fungal infection, and mycological examination should be performed, especially in children.
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Aspergillus/isolamento & purificação , Micoses/diagnóstico , Couro Cabeludo/patologia , Antifúngicos/uso terapêutico , Aspergillus/classificação , Pré-Escolar , Feminino , Humanos , Hospedeiro Imunocomprometido , Micoses/tratamento farmacológico , Micoses/microbiologia , Filogenia , Couro Cabeludo/microbiologiaRESUMO
We report a simple method for the photothermal welding of nonwoven mats of electrospun nanofibers by introducing a near-infrared (NIR) dye such as indocyanine green. By leveraging the strong photothermal effect of the dye, the nanofibers can be readily welded at their cross points or even over-welded (i.e., melted and/or fused together) to transform the porous mat into a solid film upon exposure to a NIR laser. While welding at the cross points greatly improves the mechanical strength of a nonwoven mat of nanofibers, melting and fusion of the nanofibers can be employed to fabricate a novel class of photothermal papers for laser writing or printing without chemicals or toner particles. By using a photomask, we can integrate photothermal welding with the gas foaming technique to pattern and then expand nonwoven mats into 3D scaffolds with well-defined structures. This method can be applied to different combinations of polymers and dyes, if they can be co-dissolved in a suitable solvent for electrospinning.
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Lasers , Nanofibras/química , Polímeros/química , Animais , Verde de Indocianina/química , Raios Infravermelhos , Camundongos , Células NIH 3T3 , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais/química , SoldagemRESUMO
AIMS: To fabricate a novel nanoyarn biomaterial via a dynamic liquid electrospinning system, and to simultaneously evaluate whether nanoyarn is capable of being applied as a urinary sling for future clinical transfer. METHODS: Nanoyarn was cultured with adipose-derived stem cells (ADSCs). Cell morphology and function were observed on nanoyarn. Female rats that underwent vagina dilatation (VD) and bilateral ovarian resection (BOR) were used as the urinary incontinence model. After 2 weeks, the cells-sling was fixed to the suburethra. A commercial sling that tension-free vaginal tape-obturator (TVT-O) was used as a control. The urodynamic test for leak point pressure (LPP) and histological tests were used to evaluate the sling's performance in vivo. RESULTS: The nanoyarn possessed beneficial properties and the actin filament from ADSCs, which is very similar to muscle. Rats that underwent VD and BOR maintained a low LPP, whereas the LPP in rats with VD alone recovered to normal levels within 2 weeks. LPP in the nanoyarn group gradually decreased on the three urodynamic tests post-suburethral surgery, however, the cell-laden nanoyarn maintained LPP at normal levels for 8 weeks; the TVT-O group showed a significant increase in LPP at 8 weeks. Cell-laden nanoyarn was infiltrated with more cells, collagen, and vessels than the controls. CONCLUSIONS: The nanoyarn showed sufficient efficacy to maintain LPP in urinary incontinence rat model. In addition, it improved cell infiltration, collagen and muscle development compared to TVT-O. Thus, the combination of ADSCs and a nanoyarn scaffold could be a promising tissue-engineered sling for the treatment of urinary incontinence.
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Engenharia Tecidual , Alicerces Teciduais , Incontinência Urinária por Estresse/cirurgia , Animais , Materiais Biocompatíveis , Caproatos/química , Colágeno/química , Dioxanos/química , Feminino , Lactonas/química , Ratos , Slings SuburetraisRESUMO
Natural silk protein nanoparticles are a promising biomaterial for drug delivery due to their pleiotropic properties, including biocompatibility, high bioavailability, and biodegradability. Chinese oak tasar Antheraea pernyi silk fibroin (ApF) nanoparticles are easily obtained using cations as reagents under mild conditions. The mild conditions are potentially advantageous for the encapsulation of sensitive drugs and therapeutic molecules. In the present study, silk fibroin protein nanoparticles are loaded with differently-charged small-molecule drugs, such as doxorubicin hydrochloride, ibuprofen, and ibuprofen-Na, by simple absorption based on electrostatic interactions. The structure, morphology and biocompatibility of the silk nanoparticles in vitro are investigated. In vitro release of the drugs from the nanoparticles depends on charge-charge interactions between the drugs and the nanoparticles. The release behavior of the compounds from the nanoparticles demonstrates that positively-charged molecules are released in a more prolonged or sustained manner. Cell viability studies with L929 demonstrated that the ApF nanoparticles significantly promoted cell growth. The results suggest that Chinese oak tasar Antheraea pernyi silk fibroin nanoparticles can be used as an alternative matrix for drug carrying and controlled release in diverse biomedical applications.
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Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Fibroínas/química , Nanopartículas/química , Animais , Bombyx/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Liberação Controlada de Fármacos , Fibroínas/administração & dosagem , Humanos , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Nanopartículas/uso terapêutico , Tamanho da Partícula , Seda/químicaRESUMO
Although the thiol click reaction is an attractive tool for postpolymerization modification of thiolmers, thiol groups are easily oxidized, limiting the potential for covalent immobilization of bioactive molecules. In this study, a series of biodegradable polyurethane elastomers incorporating stable cyclic disulfide groups was developed and characterized. These poly(ester urethane)urea (PEUU-SS) polymers were based on polycaprolactone diol (PCL), oxidized dl-dithiothreitol (O-DTT), lysine diisocyanate (LDI), or butyl diisocyanate (BDI), with chain extension by putrescine. The ratio of O-DTT:PCL was altered to investigate different levels of potential functionalization. PEG acrylate was employed to study the mechanism and availability of both bulk and surface click modification of PEUU-SS polymers. All synthesized PEUU-SS polymers were elastic with breaking strengths of 38-45 MPa, while the PEUU-SS(LDI) polymers were more amorphous, possessing lower moduli and relatively small permanent deformations versus PEUU-SS(BDI) polymers. Variable bulk click modification of PEUU-SS(LDI) polymers was achieved by controlling the amount of reduction reagent, and rapid reaction rates occurred using a one-pot, two-step process. Likewise, surface click reaction could be carried out quickly under mild, aqueous conditions. Furthermore, a maleimide-modified affinity peptide (TPS) was successfully clicked on the surface of an electrospun PEUU-SS(BDI) fibrous sheet, which improved endothelial progenitor cell adhesion versus corresponding unmodified films. The cyclic disulfide containing biodegradable polyurethanes described provide an option for cardiovascular and other soft tissue regenerative medicine applications where a temporary, elastic scaffold with designed biofunctionality from a relatively simple click chemistry approach is desired.
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Plásticos Biodegradáveis/química , Poliuretanos/química , Compostos de Sulfidrila/química , Dissulfetos/química , Elastômeros/química , Ureia/químicaRESUMO
BACKGROUND: Capping techniques have been used as a treatment modality for the prevention of neuroma formation and the management of neuropathic pain. However, the results are inconsistent and unpredictable. We hypothesize that this situation may be attributable, in part, to the disparities in the type of materials used to manufacturing of the conduits. METHODS: In this study, a rat model was used and the sciatic nerve was selected for evaluation. In 1 capping group, a sciatic nerve stump was capped with a nonaligned nanofiber conduit (the nonaligned group), whereas in a second capping group, the conduit was made of aligned nanofibers (the aligned group). In another group, the sciatic nerve stump was not capped as a control (the control group). The results of autotomy behavior, extent of neuroma formation, histological changes in the neuroma, and the expression of c-fos as a pain marker in the fourth lumbar spinal cord were evaluated at 8 weeks postoperatively. RESULTS: The control group presented more neuroma-like features in all the observed parameters in comparison with the 2 capping groups; of the 2 capping groups, the aligned group achieved even better outcomes than the nonaligned group. CONCLUSIONS: Our findings indicate that the aligned nanofiber conduit is a promising biomaterial for the nerve capping technique, and new treatment strategies using aligned nanofiber conduits may be developed for the management of painful amputated neuromas.
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Nanofibras/química , Neuroma/prevenção & controle , Procedimentos Neurocirúrgicos/instrumentação , Complicações Pós-Operatórias/prevenção & controle , Nervo Isquiático/cirurgia , Animais , Masculino , Regeneração Nervosa , Neuralgia/etiologia , Neuralgia/prevenção & controle , Neuroma/etiologia , Procedimentos Neurocirúrgicos/métodos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
Stem cells and scaffolds play a very important role in tissue engineering. Here, we isolated synovium-derived mesenchymal stem cells (SMSCs) from synovial membrane tissue and characterized stem-cell properties. Gelatin nanoparticles (NP) were prepared using a two-step desolvation method and then pre-mixed into different host matrix (silk fibroin (SF), gelatin (Gel), or SF-Gel mixture) to generate various 3D printed nanocomposite scaffolds (NP/SF, NP/SF-Gel, NP/Gel-1, and NP/Gel-2). The microstructure was examined by scanning electron microscopy. Biocompatibility assessment was performed through CCK-8 assay by coculturing with SMSCs at 1, 3, 7 and 14 days. According to the results, SMSCs are similar to other MSCs in their surface epitope expression, which are negative for CD45 and positive for CD44, CD90, and CD105. After incubation in lineage-specific medium, SMSCs could differentiate into chondrocytes, osteocytes and adipocytes. 3D printed nanocomposite scaffolds exhibited a good biocompatibility in the process of coculturing with SMSCs and had no negative effect on cell behavior. The study provides a strategy to obtain SMSCs and fabricate 3D printed nanocomposite scaffolds, the combination of which could be used for practical applications in tissue engineering.
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OBJECTIVE: To evaluate the mechanical property and biocompatibility of the Wnt pathway inhibitor (ICG-001) delivering collagen/poly(L-lactide-co-caprolactone) (P(LLA-CL)) scaffold for urethroplasty, and also the feasibility of inhibiting the extracellular matrix (ECM) expression in vitro and in vivo. METHODS: ICG-001 (1 mg (2 mM)) was loaded into a (P(LLA-CL)) scaffold with the co-axial electrospinning technique. The characteristics of the mechanical property and drug release fashion of scaffolds were tested with a mechanical testing machine (Instron) and high-performance liquid chromatography (HPLC). Rabbit bladder epithelial cells and the dermal fibroblasts were isolated by enzymatic digestion method. (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay) and scanning electron microscopy (SEM) were used to evaluate the viability and proliferation of the cells on the scaffolds. Fibrolasts treated with TGF-ß1 and ICG-001 released medium from scaffolds were used to evaluate the anti-fibrosis effect through immunofluorescence, real time PCR and western blot. Urethrography and histology were used to evaluate the efficacy of urethral implantation. RESULTS: The scaffold delivering ICG-001 was fabricated, the fiber diameter and mechanical strength of scaffolds with inhibitor were comparable with the non-drug scaffold. The SEM and MTT assay showed no toxic effect of ICG-001 to the proliferation of epithelial cells on the collagen/P(LLA-CL) scaffold with ICG-001. After treatment with culture medium released from the drug-delivering scaffold, the expression of Collagen type 1, 3 and fibronectin of fibroblasts could be inhibited significantly at the mRNA and protein levels. In the results of urethrography, urethral strictures and fistulas were found in the rabbits treated with non-ICG-001 delivering scaffolds, but all the rabbits treated with ICG-001-delivering scaffolds showed wide caliber in urethras. Histology results showed less collagen but more smooth muscle and thicker epithelium in urethras repaired with ICG-001 delivering scaffolds. CONCLUSION: After loading with the Wnt signal pathway inhibitor ICG-001, the Collagen/P(LLA-CL) scaffold could facilitate a decrease in the ECM deposition of fibroblasts. The ICG-001 delivering Collagen/P(LLA-CL) nanofibrous scaffold seeded with epithelial cells has the potential to be a promising substitute material for urethroplasty. Longer follow-up study in larger animals is needed in the future.
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Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Pirimidinonas/farmacologia , Alicerces Teciduais , Estreitamento Uretral/metabolismo , Estreitamento Uretral/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/química , Proliferação de Células , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Constrição Patológica/tratamento farmacológico , Constrição Patológica/metabolismo , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Fibrose/tratamento farmacológico , Masculino , Pirimidinonas/administração & dosagem , Pirimidinonas/química , Coelhos , Engenharia Tecidual , Alicerces Teciduais/química , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Uretra , Estreitamento Uretral/diagnóstico , Estreitamento Uretral/tratamento farmacológico , Estreitamento Uretral/cirurgiaRESUMO
BACKGROUND: Pine wilt disease has caused significant economic, ecological, and social losses in China, but there is a notable lack of research on the dynamic process of its propagation and diffusion over long timescales. This study revealed the spatial and temporal spread of the natural invasion of pine wilt disease through an analysis of long time series at macroscopic scales. We analysed and verified by simulations the driving mechanisms of host and wind fields in the natural spread of pine wilt disease. RESULTS: The research findings indicate that from 1982 to 2019, the number of counties affected by pine wilt disease in the Yangtze River Delta region of China exhibited a pattern of 'steady increase-fluctuation-outbreak'. The host forest played a decisive role in the natural spread of the disease, while the wind field played a supporting role. The study revealed specific contributions from various factors, where host forest landscape connectivity, host forest area share, mean wind speed, and wind frequency accounted for 31.8%, 28.7%, 22.6%, and 8.8%, respectively. The interaction of increased host forest area and increased wind speed can significantly increase the risk of pine wilt disease transmission. To validate these findings, vectorial metacellular automata simulations of pine nematode transmission in the Yangtze River Delta were conducted, yielding results with an accuracy of 0.803. CONCLUSION: By quantifying the contribution of host forest connectivity to the natural spread of pine wilt disease, this research offers a scientific foundation and innovative insights for preventing and controlling its dissemination. © 2024 Society of Chemical Industry.
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Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties, biocompatibility, biodegradability, vasculogenic ability and osteo-inductivity. The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma (PRP)-loaded gelatin methacrylate (GM) and employ them for the regeneration of large-sized bone defects. We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors (GFs) from hydrogels. The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects. For biofunction assay, the GM@PRP hydrogels significantly improved cell migration and angiogenesis. Especially, transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels. The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats. Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis, biomineralization, and collagen deposition. Based on the biocompatibility and biological function of GM@PRP hydrogels, a new strategy is provided for the regenerative repair of large-size bone defects.
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Pro-inflammatory response impairs the constructive repair of abdominal wall defects after mesh implantation. Electrospinning-aid functionalization has the potential to improve the highly orchestrated response by attenuating the over-activation of foreign body reactions. Herein, we combined poly(L-lactic acid-co-caprolactone) (PLLA-CL) with gelatin proportionally via electrospinning, with Ibuprofen (IBU) incorporation to fabricate a bilayer mesh for the repair improvement. The PLLA-CL/gelatin/IBU (PGI) mesh was characterized in vitro and implanted into the rat model with a full-thickness defect for a comprehensive evaluation in comparison to the PLLA-CL/gelatin (PG) and off-the-shelf small intestinal submucosa (SIS) meshes. The bilayer PGI mesh presented a sustained release of IBU over 21 days with degradation in vitro and developed less-intensive intraperitoneal adhesion along with a histologically weaker inflammatory response than the PG mesh after 28 days. It elicited an M2 macrophage-dominant foreign body reaction within the process, leading to a pro-remodeling response similar to the biological SIS mesh, which was superior to the PG mesh. The PGI mesh provided preponderant mechanical supports over the SIS mesh and the native abdominal wall with similar compliance. Collectively, the newly developed mesh advances the intraperitoneal applicability of electrospun meshes by guiding a pro-remodeling response and offers a feasible functionalization approach upon immunomodulation.
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Parede Abdominal , Ibuprofeno , Ratos , Animais , Ibuprofeno/farmacologia , Parede Abdominal/cirurgia , Gelatina/farmacologia , Telas Cirúrgicas , Próteses e ImplantesRESUMO
Endovascular treatment (EVT) using stents has become the primary option for severe cerebrovascular stenosis. However, considerable challenges remain to be addressed, such as in-stent restenosis (ISR) and late thrombosis. Many modified stents have been developed to inhibit the hyperproliferation of vascular smooth muscle cells (SMCs) and protect vascular endothelial cells (VECs), thereby reducing such complications. Some modified stents, such as those infused with rapamycin, have improved in preventing acute thrombosis. However, ISR and late thrombosis, which are long-term complications, remain unavoidable. Panax notoginseng saponin (PNS), a traditional Chinese medicine consisting of various compounds, is beneficial in promoting the proliferation and migration of VECs and inhibiting the proliferation of SMCs. Herein, a 3D-printed polycaprolactone (PCL) stent loaded with PNS (PNS-PCL stent) was developed based on a previous study. In vitro studies confirmed that PNS promotes the migration and proliferation of VECs, which were damaged, by increasing the expression levels of microRNA-126, p-AKT, and endothelial nitric oxide synthase. In vivo, the PNS-PCL stents maintained the patency of the carotid artery in rabbits for up to three months, outperforming the PCL stents. The PNS-PCL stents may present a new solution for the EVT of cerebrovascular atherosclerotic stenosis in the future.
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Psoriasis is an autoinflammatory dermatosis, while methotrexate (MTX) is an immunosuppressant used to treat psoriasis. However, conventional immunosuppressants may cause various side effects. Acupuncture has potential benefits in treating psoriasis based on its anti-inflammatory effects. However, the immune mechanisms underlying its effects remain unclear. In this study, imiquimod-induced psoriatic mice were used to investigate the effects and mechanisms of electroacupuncture (EA) and, in particular, its joint treatment with MTX. We found that treatment with either EA or MTX ameliorated psoriasiform skin lesions, improved skin pathology and reduced proinflammatory cytokines in the skin, while joint treatment with both EA and MTX further alleviated the skin lesions and inflammation compared to either one alone. Moreover, percentages of CD4+ IL-17A+ Th17 cells in the skin and lymph nodes were decreased by EA or MTX and further lowered by combined EA+MTX treatment. Similarly, EA or MTX also reduced their RORγt expression. On the contrary, CD4+ FoxP3+ Treg frequency in psoriatic mice was augmented by EA or MTX and further increased by the joint treatment. However, depleting Tregs mostly reversed the therapeutic effects of EA or EA plus MTX. Additionally, the phosphorylated NF-κB (p65) expression was suppressed by treatment with EA, MTX or better with EA+MTX. Meanwhile, the anti-inflammatory effects of EA plus MTX were offset by an NF-κB agonist. Thus, this study has revealed that EA cooperates with MTX to balance Th17/Treg responses and to ameliorate psoriasiform skin inflammation through suppressing NF-κB activation. Our findings may be implicated for treating human psoriasis.
Assuntos
Eletroacupuntura , Imiquimode , Metotrexato , Psoríase , Pele , Linfócitos T Reguladores , Células Th17 , Animais , Psoríase/imunologia , Psoríase/tratamento farmacológico , Psoríase/terapia , Psoríase/induzido quimicamente , Células Th17/imunologia , Células Th17/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Eletroacupuntura/métodos , Pele/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Camundongos , Modelos Animais de Doenças , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Humanos , NF-kappa B/metabolismo , Terapia Combinada , Masculino , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismoRESUMO
N-chloro-N-fluorobenzenesulfonylamide (CFBSA), was a novel chlorinating reagent, which exhibits potential antibacterial activities. In this study, CFBSA was confirmed as a wide-broad antimicrobial and bactericidal drug against different gram-negative bacteria, gram-positive bacteria and fungi, while it was found to have low cytotoxicity for eukaryotic cells. In addition, microorganism morphology assay and oxidative stress test was used to determine the antimicrobial mechanisms of CFBSA. According to the results, CFBSA probably had a target on cell membrane and killed microorganism by disrupting its cell membrane. Then, CFBSA was first combined with poly(L-lactide-co-caprolactone) (PLCL)/SF via electrospinning and applied in wound dressings. The characterization of different PLCL/SF of CFBSA-loaded nanofibrous mats was investigated by SEM, water contact angle, Fourier transform infrared spectroscopy, cell compatibility and antimicrobial test. CFBSA-loaded PLCL/SF nanofibrous mats showed excellent antimicrobial activities. In order to balance of the biocompatibility and antibacterial efficiency, SP-2.5 was selected as the ideal loading concentration for further application of CFBSA-loaded PLCL/SF. In conclusion, the electrospun CFBSA-loaded PLCL/SF nanofibrous mat with its broad-spectrum antimicrobial and bactericidal activity and good biocompatibility showed enormous potential for wound dressing.
Assuntos
Antibacterianos , Bandagens , Nanofibras , Antibacterianos/farmacologia , Antibacterianos/química , Nanofibras/química , Testes de Sensibilidade Microbiana , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cicatrização/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Teste de Materiais , Animais , Bactérias Gram-Positivas/efeitos dos fármacos , Poliésteres/química , Poliésteres/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Estresse Oxidativo/efeitos dos fármacosRESUMO
Multifunctional bioactive biomaterials with integrated bone and soft tissue regenerability hold great promise for the regeneration of trauma-affected skin and bone defects. The aim of this research was to fabricate aerogel scaffolds (GD-BF) by blending the appropriate proportions of short bioactive glass fiber (BGF), gelatin (Gel), and dopamine (DA). Electrospun polyvinyl pyrrolidone (PVP)-BGF fibers were converted into short BGF through calcination and homogenization. Microporous GD-BF scaffolds displayed good elastic deformation recovery and promoted neo-tissue formation. The DA could enable thermal crosslinking and enhance the mechanical properties and structural stability of the GD-BF scaffolds. The BGF-mediated release of therapeutic ions shorten hemostatic time (<30 s) in a rat tail amputation model and a rabbit artery injury model alongside inducing the regeneration of skin appendages (e.g., blood vessels, glands, etc.) in a full-thickness excisional defect model in rats (percentage wound closure: GD-BF2, 98 % vs. control group, 83 %) at day 14 in vitro. Taken together, these aerogel scaffolds may have significant promise for soft and hard tissue repair, which may also be worthy for the other related disciplines.