RESUMEN
Traditional bioreactor systems involve the use of three-dimensional (3D) scaffolds or stem cell aggregates, limiting the accessibility to the production of cell-secreted biomolecules. Herein, we present the use a pulse electromagnetic fields (pEMFs)-assisted wave-motion bioreactor system for the dynamic and scalable culture of human bone marrow-derived mesenchymal stem cells (hBMSCs) with enhanced the secretion of various soluble factors with massive therapeutic potential. The present study investigated the influence of dynamic pEMF (D-pEMF) on the kinetic of hBMSCs. A 30-min exposure of pEMF (10V-1Hz, 5.82 G) with 35 oscillations per minute (OPM) rocking speed can induce the proliferation (1 × 105 â 4.5 × 105) of hBMSCs than static culture. Furthermore, the culture of hBMSCs in osteo-induction media revealed a greater enhancement of osteogenic transcription factors under the D-pEMF condition, suggesting that D-pEMF addition significantly boosted hBMSCs osteogenesis. Additionally, the RNA sequencing data revealed a significant shift in various osteogenic and signaling genes in the D-pEMF group, further suggesting their osteogenic capabilities. In this research, we demonstrated that the combined effect of wave and pEMF stimulation on hBMSCs allows rapid proliferation and induces osteogenic properties in the cells. Moreover, our study revealed that D-pEMF stimuli also induce ROS-scavenging properties in the cultured cells. This study also revealed a bioactive and cost-effective approach that enables the use of cells without using any expensive materials and avoids the possible risks associated with them post-implantation.
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Reactores Biológicos , Campos Electromagnéticos , Células Madre Mesenquimatosas , Osteogénesis , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Perfilación de la Expresión Génica , Proliferación Celular , Diferenciación Celular , Células Cultivadas , TranscriptomaRESUMEN
Rapid regeneration of the injured tissue or organs is necessary to achieve the usual functionalities of the damaged parts. However, bacterial infections delay the regeneration process, a severe challenge in the personalized healthcare sector. To overcome these challenges, 3D-printable multifunctional hydrogels of Zn/tannic acid-reinforced glycol functionalized chitosan for rapid wound healing were developed. Polyphenol strengthened intermolecular connections, while glutaraldehyde stabilized 3D-printed structures. The hydrogel exhibited enhanced viscoelasticity (G'; 1.96 × 104 Pa) and adhesiveness (210 kPa). The dual-crosslinked scaffolds showed remarkable antibacterial activity against Bacillus subtilis (â¼81 %) and Escherichia coli (92.75 %). The hydrogels showed no adverse effects on human dermal fibroblasts (HDFs) and macrophages (RAW 264.7), indicating their superior biocompatibility. The Zn/TA-reinforced hydrogels accelerate M2 polarization of macrophages through the activation of anti-inflammatory transcription factors (Arg-1, VEGF, CD163, and IL-10), suggesting better immunomodulatory effects, which is favorable for rapid wound regeneration. Higher collagen deposition and rapid re-epithelialization occurred in scaffold-treated rat groups vis-à-vis controls, demonstrating superior wound healing. Taken together, the developed multifunctional hydrogels have great potential for rapidly regenerating bacteria-infected wounds in the personalized healthcare sector.
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Antibacterianos , Biopelículas , Quitosano , Escherichia coli , Hidrogeles , Impresión Tridimensional , Cicatrización de Heridas , Quitosano/química , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Animales , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Células RAW 264.7 , Escherichia coli/efectos de los fármacos , Zinc/química , Zinc/farmacología , Ratas , Bacillus subtilis/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Masculino , Macrófagos/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Ratas Sprague-DawleyRESUMEN
Photosensitizing agents have received increased attention from the medical community, owing to their higher photothermal efficiency, induction of hyperthermia, and sustained delivery of bioactive molecules to their targets. Micro/nanorobots can be used as ideal photosensitizing agents by utilizing various physical stimuli for the targeted killing of pathogens (e.g., bacteria) and cancer cells. Herein, we report sunflower-pollen-inspired spiky zinc oxide (s-ZnO)-based nanorobots that effectively kill bacteria and cancer cells under near-infrared (NIR) light irradiation. The as-fabricated s-ZnO was modified with a catechol-containing photothermal agent, polydopamine (PDA), to improve its NIR-responsive properties, followed by the addition of antimicrobial (e.g., tetracycline/TCN) and anticancer (e.g., doxorubicin/DOX) drugs. The fabricated s-ZnO/PDA@Drug nanobots exhibited unique locomotory behavior with an average speed ranging from 13 to 14 µm/s under 2.0 W/cm2 NIR light irradiation. Moreover, the s-ZnO/PDA@TCN nanobots exhibited superior antibacterial activity against E. coli and S. epidermidis under NIR irradiation. The s-ZnO/PDA@DOX nanobots also displayed sufficient reactive oxygen species (ROS) amplification in B16F10 melanoma cells and induced apoptosis under NIR light, indicating their therapeutic efficacy. We hope the sunflower pollen-inspired s-ZnO nanorobots have tremendous potential in biomedical engineering from the phototherapy perspective, with the hope to reduce pathogen infections.
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Antibacterianos , Antineoplásicos , Materiales Biocompatibles , Ensayos de Selección de Medicamentos Antitumorales , Helianthus , Tamaño de la Partícula , Fármacos Fotosensibilizantes , Óxido de Zinc , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Helianthus/química , Antineoplásicos/farmacología , Antineoplásicos/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Óxido de Zinc/química , Óxido de Zinc/farmacología , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Polen/química , Escherichia coli/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Indoles/química , Indoles/farmacología , Animales , Ratones , Doxorrubicina/farmacología , Doxorrubicina/química , Rayos InfrarrojosRESUMEN
Macrophages play an essential role in immunotherapy and tissue regeneration owing to their remarkable plasticity and diverse functions. Recent bioengineering developments have focused on using external physical stimuli such as electric and magnetic fields, temperature, and compressive stress, among others, on micro/nanostructures to induce macrophage polarization, thereby increasing their therapeutic potential. However, it is difficult to find a concise review of the interaction between physical stimuli, advanced micro/nanostructures, and macrophage polarization. This review examines the present research on physical stimuli-induced macrophage polarization on micro/nanoplatforms, emphasizing the synergistic role of fabricated structure and stimulation for advanced immunotherapy and tissue regeneration. A concise overview of the research advancements investigating the impact of physical stimuli, including electric fields, magnetic fields, compressive forces, fluid shear stress, photothermal stimuli, and multiple stimulations on the polarization of macrophages within complex engineered structures, is provided. The prospective implications of these strategies in regenerative medicine and immunotherapeutic approaches are highlighted. This review will aid in creating stimuli-responsive platforms for immunomodulation and tissue regeneration.
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Macrófagos , Macrófagos/metabolismo , Macrófagos/citología , Humanos , Animales , Nanoestructuras/química , Medicina Regenerativa/métodos , Campos Magnéticos , Ingeniería de Tejidos/métodosRESUMEN
The skin serves as the body's outermost barrier and is the largest organ, providing protection not only to the body but also to various internal organs. Owing to continuous exposure to various external factors, it is susceptible to damage that can range from simple to severe, including serious types of wounds such as burns or chronic wounds. Macrophages play a crucial role in the entire wound-healing process and contribute significantly to skin regeneration. Initially, M1 macrophages infiltrate to phagocytose bacteria, debris, and dead cells in fresh wounds. As tissue repair is activated, M2 macrophages are promoted, reducing inflammation and facilitating restoration of the dermis and epidermis to regenerate the tissue. This suggests that extracellular matrix (ECM) promotes cell adhesion, proliferation, migrationand macrophage polarization. Among the numerous strategies, electrospinning is a versatile technique for obtaining ECM-mimicking structures with anisotropic and isotropic topologies of micro/nanofibers. Various electrospun biomaterials influence macrophage polarization based on their isotropic or anisotropic topologies. Moreover, these fibers possess a high surface-area-to-volume ratio, promoting the effective exchange of vital nutrients and oxygen, which are crucial for cell viability and tissue regeneration. Micro/nanofibers with diverse physical and chemical properties can be tailored to polarize macrophages toward skin regeneration and wound healing, depending on specific requirements. This review describes the significance of micro/nanostructures for activating macrophages and promoting wound healing.
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Matriz Extracelular , Macrófagos , Nanofibras , Cicatrización de Heridas , Nanofibras/química , Cicatrización de Heridas/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Humanos , Animales , Anisotropía , Polaridad Celular/efectos de los fármacos , Piel/lesiones , Piel/metabolismoRESUMEN
Conductive hydrogels (CHs) are promising alternatives for electrical stimulation of cells and tissues in biomedical engineering. Wound healing and immunomodulation are complex processes that involve multiple cell types and signaling pathways. 3D printable conductive hydrogels have emerged as an innovative approach to promote wound healing and modulate immune responses. CHs can facilitate electrical and mechanical stimuli, which can be beneficial for altering cellular metabolism and enhancing the efficiency of the delivery of therapeutic molecules. This review summarizes the recent advances in 3D printable conductive hydrogels for wound healing and their effect on macrophage polarization. This report also discusses the properties of various conductive materials that can be used to fabricate hydrogels to stimulate immune responses. Furthermore, this review highlights the challenges and limitations of using 3D printable CHs for future material discovery. Overall, 3D printable conductive hydrogels hold excellent potential for accelerating wound healing and immune responses, which can lead to the development of new therapeutic strategies for skin and immune-related diseases.
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Hidrogeles , Ingeniería de Tejidos , Hidrogeles/farmacología , Conductividad Eléctrica , Cicatrización de Heridas , MacrófagosRESUMEN
Recent studies indicate that mitochondrial dysfunctions and DNA damage have a critical influence on cell survival, which is considered one of the therapeutic targets for cancer therapy. In this study, we demonstrated a comparative study of the effect of polyphenolic carbon quantum dots (CQDs) on in vitro and in vivo antitumor efficacy. Dual emissive (green and yellow) shape specific polyphenolic CQDs (G-CQDs and Y-CQDs) were synthesized from easily available nontoxic precursors (phloroglucinol), and the antitumor property of the as-synthesized probe was investigated as compared to round-shaped blue emissive CQDs (B-CQDs) derived from well-reported precursor citric acid and urea. The B-CQDs had a nuclei-targeting property, and G-CQDs and Y-CQDs had mitochondria-targeting properties. We have found that the polyphenol containing CQDs (at a dose of 100 µg mL-1) specifically attack mitochondria by excess accumulation, altering the metabolism, inhibiting branching pattern, imbalanced Bax/Bcl-2 homeostasis, and ultimately generating oxidative stress levels, leading to oxidative stress-induced cell death in cancer cells in vitro. We show that G-CQDs are the main cause of oxidative stress in cancer cells because of their ability to produce sufficient â¢OH- and 1O2 radicals, evidenced by electron paramagnetic resonance spectroscopy and a terephthalic acid test. Moreover, the near-infrared absorption properties of the CQDs were exhibited in two-photon (TP) emission, which was utilized for TP cellular imaging of cancer cells without photobleaching. The in vivo antitumor test further discloses that intratumoral injection of G-CQDs can significantly augment the treatment efficacy of subcutaneous tumors without any adverse effects on BalB/c nude mice. We believe that shape-specific polyphenolic CQD-based nanotheranostic agents have a potential role in tumor therapy, thus proving an insight on treatment of malignant cancers.
RESUMEN
One of the significant challenges in bone tissue engineering (BTE) is the healing of traumatic tissue defects owing to the recruitment of local infection and delayed angiogenesis. Herein, a 3D printable multi-functional hydrogel composing polyphenolic carbon quantum dots (CQDs, 100 µg mL-1 ) and gelatin methacryloyl (GelMA, 12 wt%) is reported for robust angiogenesis, bone regeneration and anti-tumor therapy. The CQDs are synthesized from a plant-inspired bioactive molecule, 1, 3, 5-trihydroxybenzene. The 3D printed GelMA-CQDs hydrogels display typical shear-thinning behavior with excellent printability. The fabricated hydrogel displayed M2 polarization of macrophage (Raw 264.7) cells via enhancing anti-inflammatory genes (e.g., IL-4 and IL10), and induced angiogenesis and osteogenesis of human bone mesenchymal stem cells (hBMSCs). The bioprinted hBMSCs are able to produce vessel-like structures after 14 d of incubation. Furthermore, the 3D printed hydrogel scaffolds also show remarkable near infra-red (NIR) responsive properties under 808 nm NIR light (1.0 W cm-2 ) irradiation with controlled release of antitumor drugs (≈49%) at pH 6.5, and thereby killing the osteosarcoma cells. Therefore, it is anticipated that the tissue regeneration and healing ability with therapeutic potential of the GelMA-CQDs scaffolds may provide a promising alternative for traumatic tissue regeneration via augmenting angiogenesis and accelerated immunomodulation.
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Hidrogeles , Células Madre Mesenquimatosas , Humanos , Hidrogeles/farmacología , Hidrogeles/química , Regeneración Ósea , Osteogénesis , Ingeniería de Tejidos , Gelatina/farmacología , Gelatina/química , Macrófagos , Apoptosis , Andamios del Tejido/química , Impresión TridimensionalRESUMEN
Biomimetic soft hydrogels used in bone tissue engineering frequently produce unsatisfactory outcomes. Here, it is investigated how human bone-marrow-derived mesenchymal stem cells (hBMSCs) differentiated into early osteoblasts on remarkably soft 3D hydrogel (70 ± 0.00049 Pa). Specifically, hBMSCs seeded onto cellulose nanocrystals incorporated methacrylate gelatin hydrogels are subjected to pulsatile pressure stimulation (PPS) of 5-20 kPa for 7 days. The PPS stimulates cellular processes such as mechanotransduction, cytoskeletal distribution, prohibition of oxidative stress, calcium homeostasis, osteogenic marker gene expression, and osteo-specific cytokine secretions in hBMSCs on soft substrates. The involvement of Piezo 1 is the main ion channel involved in mechanotransduction. Additionally, RNA-sequencing results reveal differential gene expression concerning osteogenic differentiation, bone mineralization, ion channel activity, and focal adhesion. These findings suggest a practical and highly scalable method for promoting stem cell commitment to osteogenesis on soft matrices for clinical reconstruction.
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Diferenciación Celular , Células Madre Mesenquimatosas , Osteogénesis , Humanos , Células Cultivadas , Hidrogeles/química , Células Madre Mesenquimatosas/fisiología , Impresión Tridimensional , TranscriptomaRESUMEN
In recent years, three-dimensional (3D) bioprinting of conductive hydrogels has made significant progress in the fabrication of high-resolution biomimetic structures with gradual complexity. However, the lack of an effective cross-linking strategy, ideal shear-thinning, appropriate yield strength, and higher print fidelity with excellent biofunctionality remains a challenge for developing cell-laden constructs, hindering the progress of extrusion-based 3D printing of conductive polymers. In this study, a highly stable and conductive bioink was developed based on polypyrrole-grafted gelatin methacryloyl (GelMA-PPy) with a triple cross-linking (thermo-photo-ionically) strategy for direct ink writing-based 3D printing applications. The triple-cross-linked hydrogel with dynamic semi-inner penetrating polymer network (semi-IPN) displayed excellent shear-thinning properties, with improved shape fidelity and structural stability during 3D printing. The as-fabricated hydrogel ink also exhibited "plug-like non-Newtonian" flow behavior with minimal disturbance. The bioprinted GelMA-PPy-Fe hydrogel showed higher cytocompatibility (93%) of human bone mesenchymal stem cells (hBMSCs) under microcurrent stimulation (250 mV/20 min/day). Moreover, the self-supporting and tunable mechanical properties of the GelMA-PPy bioink allowed 3D printing of high-resolution biological architectures. As a proof of concept, we printed a full-thickness rat bone model to demonstrate the structural stability. Transcriptomic analysis revealed that the 3D bioprinted hBMSCs highly expressed gene hallmarks for NOTCH/mitogen-activated protein kinase (MAPK)/SMAD signaling while down-regulating the Wnt/ß-Catenin and epigenetic signaling pathways during osteogenic differentiation for up to 7 days. These results suggest that the developed GelMA-PPy bioink is highly stable and non-toxic to hBMSCs and can serve as a promising platform for bone tissue engineering applications.
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Bioimpresión , Hidrogeles , Ratas , Animales , Humanos , Hidrogeles/química , Polímeros , Osteogénesis , Pirroles , Bioimpresión/métodos , Gelatina/química , Ingeniería de Tejidos/métodos , Impresión Tridimensional , Andamios del Tejido/químicaRESUMEN
Nanocellulose application has been increasing owing to its appealing physicochemical properties. Monitoring of the crystallinity, surface topography, and reactivity of this high-aspect-ratio nanomaterial is crucial for efficient tissue engineering. Controlling macrophage polarization phenotype remains a challenge in regenerative medicine and tissue engineering. Herein, we monitored the effects of shape-regulated (rod and spherical) nanocellulose on the macrophage modulatory potential of RAW 246.7 cells in vitro. Spherical nanocellulose (s-NC) exhibited higher thermal stability and biocompatibility than rod nanocellulose. Macrophage polarization was profoundly affected by nanocellulose topography and incubation period. M2 polarization was observed in vitro after 1 day of treatment with s-NC, followed by M1 polarization after treatment for longer periods. Transcriptome analysis similarly revealed that M1 polarization was dominant after 1 day h of incubation with both nanocellulose types. These findings demonstrate that macrophage polarization can be controlled by selecting suitable nanocellulose shape and incubation time for desired applications.
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Nanosferas , Nanoestructuras , Celulosa/farmacología , Celulosa/química , Nanoestructuras/química , Macrófagos , Ingeniería de TejidosRESUMEN
Upregulation of certain enzymes, such as collagenase, tyrosinase, and elastase, is triggered by several extrinsic environmental factors, such as temperature, UV radiation, humidity, and stress, and leads to elasticity loss and skin pigmentation. Herein, dual-emissive polyaromatic carbon quantum dots (CQDs) with abundant phenolic moieties, that is green and yellow CQDs (G-CQDs and Y-CQDs, respectively), were prepared using a three-fold symmetric molecule, 1,3,5-trihydroxybenzene. The significant inhibition efficacy of the fabricated CQDs against collagenase, elastase, and tyrosinase, which play important roles in skin aging, revealed their excellent antiaging potential. Y-CQDs with large polyphenolic-polyaromatic domains and abundant -OH groups exhibited high enzyme inhibitory efficacy against skin aging, and their collagenase, elastase, and tyrosinase inhibitory efficacies were â¼75 ± 4.2%, â¼52 ± 3.1%, and â¼35.3 ± 4.2%, respectively, at a concentration of 100 µg mL-1. The most critical factor that delays wound healing is oxidative stress, which is caused by the overproduction of free radicals around inflamed tissue. CQDs were effective in suppressing UV-induced reactive oxygen species at the cellular level and improved the cell viability. Subsequently, CQD-incorporated dual-emissive biocompatible gelatin-methacryloyl hydrogels were constructed as wound dressing materials to promote wound healing via inducing the proliferation of fibroblasts, enhancing cell migration and alleviating inflammation and to provide antiaging benefits. Our results demonstrated that the fabricated CQDs with remarkable optical features, low cytotoxicity, and excellent antioxidant and antiaging properties can be used as bio-imaging probes, antiaging agents, and wound dressing materials for oxidative stress-related diseases in the nanomedicine and cosmetics industries.
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Puntos Cuánticos , Carbono , Hidrogeles , Monofenol Monooxigenasa , Estrés Oxidativo , Elastasa Pancreática , Polifenoles/farmacología , Cicatrización de HeridasRESUMEN
Biopolymers-induced immune microenvironment exhibited prominent effects on bone regeneration. Osteo-immunomodulatory responses of cellulose nanoparticles incorporated chitosan hydrogel scaffolds have not yet been reported. The objective of this study was to monitor the synergistic effects of silk fibroin and cellulose nanoparticles on the immune-modulatory behavior of chitosan biopolymer scaffolds. 3D-printed biodegradable cellulose nanoparticles-reinforced chitosan/silk fibroin (CS/SF/CNPs) scaffolds were fabricated and characterized by different spectroscopic techniques. The improved rheological and recovery strength was observed in CS/SF/CNPs hydrogels than pure polymer hydrogels. A significant shift from M1 â M2 macrophages polarization occurred in the CS/SF/CNPs scaffolds treated groups than the control after 3 days of incubation, showing its immune-modulatory potential. Osteo-immunomodulatory effects of the fabricated scaffolds were analyzed on human bone marrow-derived mesenchymal stem cells (hBMSCs), with macrophages-derived conditioned media (M-CM). Enhanced bone regeneration was observed in the calvaria defect rat model, indicating that the fabricated scaffolds are promising materials for bone-healing applications.
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Quitosano , Fibroínas , Nanopartículas , Animales , Regeneración Ósea , Celulosa/química , Celulosa/farmacología , Quitosano/química , Fibroínas/química , Macrófagos , Nanopartículas/química , Osteogénesis , Ratas , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
Graphene is a two-dimensional sp2 hybridized carbon material that has attracted tremendous attention for its stimuli-responsive applications, owing to its high surface area and excellent electrical, optical, thermal, and mechanical properties. The physicochemical properties of graphene can be tuned by surface functionalization. The biomedical field pays special attention to stimuli-responsive materials due to their responsive abilities under different conditions. Stimuli-responsive materials exhibit great potential in changing their behavior upon exposure to external or internal factors, such as pH, light, electric field, magnetic field, and temperature. Graphene-based materials, particularly graphene oxide (GO), have been widely used in stimuli-responsive applications due to their superior biocompatibility compared to other forms of graphene. GO has been commonly utilized in tissue engineering, bioimaging, biosensing, cancer therapy, and drug delivery. GO-based stimuli-responsive platforms for wound healing applications have not yet been fully explored. This review describes the effects of different stimuli-responsive factors, such as pH, light, temperature, and magnetic and electric fields on GO-based materials and their applications. The wound healing applications of GO-based materials is extensively discussed with cancer therapy and drug delivery.
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Tecnología Biomédica , Grafito/química , Animales , Biopelículas , Sistemas de Liberación de Medicamentos , Humanos , Concentración de Iones de Hidrógeno , Neoplasias/terapiaRESUMEN
Naturally-derived proteins or peptides are promising biopolymers for tissue engineering applications owing to their health-promoting activity. Herein, we extracted proteins (~90%) from two-spotted cricket (Gryllus bimaculatus) and evaluated their osteoinductive potential in human bone marrow-derived mesenchymal stem cells (hBMSCs) under in vitro conditions. The extracted protein isolate was analyzed for the amino acid composition and the mass distribution of the constituent peptide fraction. Fourier transform infrared (FTIR) spectroscopy was used to determine the presence of biologically significant functional groups. The cricket protein isolate (CPI) exhibited characteristic protein peaks in the FTIR spectrum. Notably, an enhanced cell viability was observed in the presence of the extracted proteins, showing their biocompatibility. The CPI also exhibited antioxidant properties in a concentration-dependent manner. More significant mineralization was observed in the CPI-treated cells than in the control, suggesting their osteoinductive potential. The upregulation of the osteogenic marker genes (Runx2, ALP, OCN, and BSP) in CPI treated media compared with the control supports their osteoinductive nature. Therefore, cricket-derived protein isolates could be used as functional protein isolate for tissue engineering applications, especially for bone regeneration.
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Antioxidantes/metabolismo , Diferenciación Celular , Proteínas de Insectos/administración & dosificación , Células Madre Mesenquimatosas/citología , Osteogénesis , Extractos de Tejidos/farmacología , Animales , Células Cultivadas , Gryllidae , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Ingeniería de TejidosRESUMEN
Carbon nanotubes (CNTs) have attracted significant interest for various applications owing to their superior physicochemical properties. The unzipping of multi-walled carbon nanotubes was accomplished by strong acid treatment. The solution of unzipped carbon nanotubes (u-CNTs) was homogeneous and stable. The u-CNTs were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. The dimensions and morphologies of the synthesized u-CNTs were examined by transmission electron microscopy and scanning electron microscopy. The u-CNTs exhibited increased zeta potential and diameter compared with pure CNTs. A decrease in the thermal stability was observed in the u-CNTs compared with pure CNTs. The u-CNTs exhibited better biocompatibility than pure CNTs in the presence of bone marrow-derived mesenchymal stem cells, showing improved biocompatibility. The u-CNT-treated media generated lower amounts of reactive oxygen species than pure CNTs. Enhanced mineralization was observed in the u-CNT-treated groups compared with the pure CNTs and the control, indicating its better osteogenic potential. The upregulation of osteogenic-associated gene markers in u-CNT groups compared with pure CNTs confirms their superior osteogenic potential. Thus, u-CNTs are potential candidates for tissue engineering applications, especially bone tissue.
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Nanotubos de Carbono/química , Osteogénesis , Ingeniería de Tejidos , Fosfatasa Alcalina/metabolismo , Animales , Calcificación Fisiológica , Muerte Celular , Supervivencia Celular , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Nanotubos de Carbono/ultraestructura , Especies Reactivas de Oxígeno/metabolismo , Temperatura , Difracción de Rayos XRESUMEN
Mushrooms with enhanced medicinal properties focus on finding such compounds that could modulate the human body's immune systems. Mushrooms have antimicrobial, antidiabetic, antiviral, hepatoprotective, antitumor, and immunomodulatory properties due to the presence of various bioactive components. ß-glucans are the major constituent of the mushroom cell wall and play a significant role in their biological activity. This review described the techniques used in the extraction of the active ingredients from the mushroom. We highlighted the structure of the bioactive polysaccharides present in the mushrooms. Therapeutic applications of different mushrooms were also described. It is interesting to note that mushrooms have the potential sources of many bioactive products that can regulate immunity. Thus, the development of functional medicinal food based on the mushroom is vital for human welfare.
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Agaricales/química , Antineoplásicos/uso terapéutico , Productos Biológicos/uso terapéutico , Inmunoterapia/métodos , Animales , HumanosRESUMEN
Most bone tissue engineering models fail to demonstrate the complex cellular functions of living bone; therefore, most translational studies on bone tissue are performed in live models. To reduce the need for live models, we developed a stimulated microchip model for monitoring protein secretion during osteogenesis using human mesenchymal stem cells (hMSCs). We established a bone microchip system for monitoring the in vitro differentiation and sensing the secreted proteins of hMSCs under a sinusoidal electromagnetic field (SEMF), which ameliorates bone healing in a biomimetic natural bone matrix. A 3 V-1 Hz SEMF biophysically stimulated osteogenesis by activating ERK-1/2 and promoting phosphorylation of p38 MAPK kinases. Exposure to a 3 V-1 Hz SEMF upregulated the expression of osteogenesis-related genes and enhanced the expression of key osteoregulatory proteins. We identified 23 proteins that were differentially expressed in stimulated human bone marrow mesenchymal stem cell secretomes or were absent in the control groups. Our on-chip stimulation technology is easy to use, versatile, and nondisruptive and should have diverse applications in regenerative medicine and cell-based therapies.
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Campos Electromagnéticos , Células Madre Mesenquimatosas , Células de la Médula Ósea , Células Cultivadas , Humanos , Osteogénesis/fisiologíaRESUMEN
Chitosan-based hydrogels have received significant interest in tissue engineering and regenerative medicine applications owing to their superior biocompatibility. However, their applications are restricted owing to their weak mechanical strength. Cellulose nanocrystals (CNCs) are often explored as reinforcing agents to improve the native properties of polymers owing to their superior physicochemical properties. We fabricated a multi-functional hydrogel scaffold of chitosan/CNCs by incorporating different amounts of CNCs into a chitosan (CH) hydrogel. Significant enhancement in the mechanical strength was noted in the CH/CNCs as compared to that in pure CH hydrogel scaffolds. The cytocompatibility of the fabricated scaffolds was monitored in the presence of bone-marrow-derived mesenchymal stem cells (BMSCs). Improved cell viability and mineralization were observed with CH/CNC hydrogel scaffolds than those with pure CH hydrogel scaffolds. Enhanced osteogenic-related gene expression was observed in the CH/CNC hydrogel scaffold environment than that in the control, indicating their osteogenic potential, in addition to enhanced antibacterial activity. Developed composite scaffolds exhibited improved sustained drug release compared to that by pure polymer scaffolds, and this was more sustained in the scaffolds with higher CNC content. Therefore, the fabricated scaffolds may have been used in tissue engineering for osteogenesis, as antibacterial agents, and in sustained drug delivery.
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Antibacterianos/química , Materiales Biocompatibles/química , Celulosa/química , Quitosano/química , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Andamios del Tejido/química , Animales , Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Materiales Biocompatibles/aislamiento & purificación , Materiales Biocompatibles/farmacología , Células Cultivadas , Celulosa/administración & dosificación , Celulosa/aislamiento & purificación , Celulosa/farmacología , Quitosano/administración & dosificación , Quitosano/aislamiento & purificación , Quitosano/farmacología , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Liberación de Fármacos , Hemólisis/efectos de los fármacos , Humanos , Hidrogeles/química , Ensayo de Materiales , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , Oryza/química , Osteogénesis/efectos de los fármacos , ARN/genética , ARN/aislamiento & purificaciónRESUMEN
The osteogenic differentiation of stem cells is profoundly affected by their microenvironmental conditions. The differentiation behavior of stem cells can be tuned by changing the niche environments. The proteins or peptides that are derived by living organisms facilitate the osteogenic differentiation of stem cells. Here, we have evaluated the osteoinductive and antioxidative potential of the Protaetia brevitarsis seulensis insect-derived protein for human bone marrow-derived mesenchymal stem cells (hBMSCs). The amino acid contents in the isolated protein were determined by an amino acid analyzer. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were used to analyze the extract's functional groups and surface morphology. The extracted protein exhibited 51.08% ß-sheet conformation. No adverse effects were observed in extract-treated cells, indicating their biocompatibility. The protein isolate showed an excellent antioxidative property. Besides this, an enhancement in the hBMSCs' mineralization has been observed in the presence of treated protein isolates. Notably, osteogenic marker genes and proteins were effectively expressed in the treated cells. These results indicated that the P. brevitarsis-derived protein isolate can be used as a potential antioxidative biomaterial for bone tissue engineering applications.