RESUMO
The human nervous system is an incredibly intricate physiological network, and neural cells lack the ability to repair and regenerate after a brain injury. 3-dimensional (3D) bioprinting technology offers a promising strategy for constructing biomimetic organ constructs and in vitro brain/disease models. The bioink serves as a pivotal component that emulates the microenvironment of biomimetic construct and exerts a profound influence on cellular behaviors. In this study, a series of mechanically adjustable and dual crosslinking bioinks were developed using photocrosslinkable methacrylated silk fibroin (SilMA) in combination with the ionic crosslinking material, pectin, or pectin methacryloyl (PecMA) with silk fibroin (SF) supplementation. SilMA/pectin exhibited superior properties, with SilMA providing biocompatibility and adjustable mechanical properties, while the addition of pectin enhanced printability. The porous structure supported neural cell growth, and 15 % SilMA/0.5 % pectin bioinks displayed excellent printability and shape fidelity. Neural stem/progenitor cells (NSPCs)-loaded bioinks were used to construct a 3D brain model, demonstrating sustained vitality and high neuronal differentiation without the need for growth factors. The SilMA/pectin bioinks demonstrated adjustable mechanical properties, favorable biocompatibility, and an environment highly conducive to neural induction, offering an alternative approach for neural tissue engineering applications or in vitro brain models.
Assuntos
Bioimpressão , Fibroínas , Células-Tronco Neurais , Pectinas , Impressão Tridimensional , Esferoides Celulares , Pectinas/química , Fibroínas/química , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Bioimpressão/métodos , Esferoides Celulares/citologia , Alicerces Teciduais/química , Animais , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Diferenciação Celular/efeitos dos fármacos , TintaRESUMO
One possible solution against the accumulation of petrochemical plastics in natural environments is to develop biodegradable plastic substitutes using natural components. However, discovering all-natural alternatives that meet specific properties, such as optical transparency, fire retardancy and mechanical resilience, which have made petrochemical plastics successful, remains challenging. Current approaches still rely on iterative optimization experiments. Here we show an integrated workflow that combines robotics and machine learning to accelerate the discovery of all-natural plastic substitutes with programmable optical, thermal and mechanical properties. First, an automated pipetting robot is commanded to prepare 286 nanocomposite films with various properties to train a support-vector machine classifier. Next, through 14 active learning loops with data augmentation, 135 all-natural nanocomposites are fabricated stagewise, establishing an artificial neural network prediction model. We demonstrate that the prediction model can conduct a two-way design task: (1) predicting the physicochemical properties of an all-natural nanocomposite from its composition and (2) automating the inverse design of biodegradable plastic substitutes that fulfils various user-specific requirements. By harnessing the model's prediction capabilities, we prepare several all-natural substitutes, that could replace non-biodegradable counterparts as exhibiting analogous properties. Our methodology integrates robot-assisted experiments, machine intelligence and simulation tools to accelerate the discovery and design of eco-friendly plastic substitutes starting from building blocks taken from the generally-recognized-as-safe database.
RESUMO
Microfluidics-based organs-on-a-chip offer a promising method for dynamic and 3-dimensional (3D) cell culture to evaluate the cell behaviors within the biomimetic environment. The purpose of this study was to establish neural network connections in a 3D neural stem cell (NSC)-based system with an interstitial level of flow for simulating the brain microenvironment toward a dynamic amyloid-ß (Aß) induced neuronal toxic model on a chip and to compare the biological effects and neurite dysfunction between static and dynamic systems. The brain-on-a-chip system consisted of an impedance analyzing layer, a structured well with a connected channel, and an interface coating with polypeptide films fabricated with modification based on our previous study. The cytotoxicity and percentage of neuron/astrocyte differentiation were all compared in both static and dynamic brain-on-a-chip systems. Reactive oxygen species production, neuron marker expression and neurotransmitter-acetylcholine release were all compared to evaluate functional neurite losses in both static and dynamic systems with/without Aß addition. Moreover, real-time impedance recording was used to consecutively monitor the neurite connection/disconnection in both static and dynamic brain-on-a-chip systems. The NSC-based dynamic brain-on-a-chip may enable the application of different neurodegenerative disease in vitro models for pathogenesis studies, drug discovery and novel therapeutic method development.
Assuntos
Células-Tronco Neurais , Doenças Neurodegenerativas , Humanos , Peptídeos beta-Amiloides/toxicidade , Dispositivos Lab-On-A-Chip , NeurôniosRESUMO
An MXene is a novel two-dimensional transition metal carbide or nitride, with a typical formula of Mn+1XnTx (M = transition metals, X = carbon or nitrogen, and T = functional groups). MXenes have found wide application in biomedicine and biosensing, owing to their high biocompatibility, abundant reactive surface groups, good conductivity, and photothermal properties. Applications include photo- and electrochemical sensors, energy storage, and electronics. This review will highlight recent applications of MXene and MXene-derived materials in drug delivery, tissue engineering, antimicrobial activity, and biosensors (optical and electrochemical). We further elaborate on recent developments in utilizing MXenes for photothermal cancer therapy, and we explore multimodal treatments, including the integration of chemotherapeutic agents or magnetic nanoparticles for enhanced therapeutic efficacy. The high surface area and reactivity of MXenes provide an interface to respond to the changes in the environment, allowing MXene-based drug carriers to respond to changes in pH, reactive oxygen species (ROS), and electrical signals for controlled release applications. Furthermore, the conductivity of MXene enables it to provide electrical stimulation for cultured cells and endows it with photocatalytic capabilities that can be used in antibiotic applications. Wearable and in situ sensors incorporating MXenes are also included. Major challenges and future development directions of MXenes in biomedical applications are also discussed. The remarkable properties of MXenes will undoubtedly lead to their increasing use in the applications discussed here, as well as many others.
Assuntos
Antibacterianos , Carbono , Nitritos , Elementos de Transição , Terapia Combinada , Portadores de FármacosRESUMO
Endogenous signals, namely nitric oxide (NO) and electrons, play a crucial role in regulating cell fate as well as the vascular and neuronal systems. Unfortunately, utilizing NO and electrical stimulation in clinical settings can be challenging due to NO's short half-life and the invasive electrodes required for electrical stimulation. Additionally, there is a lack of tools to spatiotemporally control gas release and electrical stimulation. To address these issues, an "electromagnetic messenger" approach that employs on-demand high-frequency magnetic field (HFMF) to trigger NO release and electrical stimulation for restoring brain function in cases of traumatic brain injury is introduced. The system comprises a NO donor (poly(S-nitrosoglutathione), pGSNO)-conjugated on a gold yarn-dynamos (GY) and embedded in an implantable silk in a microneedle. When subjected to HFMF, conductive GY induces eddy currents that stimulate the release of NO from pGSNO. This process significantly enhances neural stem cell (NSC) synapses' differentiation and growth. The combined strategy of using NO and electrical stimulation to inhibit inflammation, angiogenesis, and neuronal interrogation in traumatic brain injury is demonstrated in vivo.
Assuntos
Lesões Encefálicas Traumáticas , Células-Tronco Neurais , Humanos , Óxido Nítrico , Ouro , Neurônios/fisiologia , Lesões Encefálicas Traumáticas/terapiaRESUMO
Severe injuries to the peripheral nervous system (PNS) require Schwann cells to aid in neuronal regeneration. Low-frequency electrical stimulation is known to induce the cogrowth of neurons and Schwann cells in an injured PNS. However, the correlations between electrical stimulation and Schwann cell viability are complex and not well understood. In this work, we develop a machine learning (ML)-integrated workflow that uses conductive hydrogel biointerfaces to evaluate the impacts of fabrication parameters and electrical stimulation on the Schwann cell viability. First, a hydrogel array with varying MXene and peptide loadings is fabricated, which serves as conductive biointerfaces to incubate Schwann cells and introduce various electrical stimulation (at different voltages and frequencies). Upon specific fabrication parameters and stimulation, the cell viability is evaluated and input into an artificial neural network model to train the model. Additionally, a data augmentation method is applied to synthesize 1000-fold virtual data points, enabling the construction of a high-accuracy prediction model (with a testing mean absolute error ≤11%). By harnessing the model's predictive power, we can accurately predict Schwann cell viability based on a given set of fabrication/stimulation parameters. Finally, the SHapley Additive exPlanations model interpretation provides several data-scientific insights that are validated by microscopic cellular observations. Our hybrid approach, involving conductive biointerface fabrication, ML algorithms, and data analysis, offers an unconventional platform to construct a preclinical prediction model at the cellular level.
RESUMO
Traumatic brain injury (TBI) triggers inflammatory response and glial scarring, thus substantially hindering brain tissue repair. This process is exacerbated by the accumulation of activated immunocytes at the injury site, which contributes to scar formation and impedes tissue repair. In this study, a mussel-inspired nitric oxide-release microreservoir (MINOR) that combines the features of reactive oxygen species (ROS) scavengers and sustained NO release to promote angiogenesis and neurogenesis is developed for TBI therapy. The injectable MINOR fabricated using a microfluidic device exhibits excellent monodispersity and gel-like self-healing properties, thus allowing the maintenance of its structural integrity and functionality upon injection. Furthermore, polydopamine in the MINOR enhances cell adhesion, significantly reduces ROS levels, and suppresses inflammation. Moreover, a nitric oxide (NO) donor embedded into the MINOR enables the sustained release of NO, thus facilitating angiogenesis and mitigating inflammatory responses. By harnessing these synergistic effects, the biocompatible MINOR demonstrates remarkable efficacy in enhancing recovery in mice. These findings benefit future therapeutic interventions for patients with TBI.
RESUMO
Silk fibroin (SF) has good biocompatibility, degradability and mechanical properties. In this study, SF-based microneedle (MN) patches were fabricated as stromal cell-derived factor-1 (SDF-1) carriers that may be used for adipose stem cell (ASC) recruitment. Therefore, SF was chosen as the main MN material to achieve sustained drug release. In addition, the variations in SF-based MN crystallinity after water annealing treatment were also determined. The results indicated that SF-based MN patches were successfully fabricated with a 3M™ commercial template and Polydimethylsiloxane mold. Through optical coherence tomography, it was found that all of the SF-based MN patches prepared in this study had sufficient strength to penetrate the skin to a depth of approximately 400 µm. Sustained release of the model drug-dextran from the SF-based MNs was demonstrated. Although SF-based MNs release SDF-1 in a sustained manner, the quantity released can be regulated and improved. Subsequently, dual-layer SDF-1-loaded MNs fabricated with a gelatin tip and SF body were prepared to enhance SDF-1 release for ASC recruitment. SF-based MNs can show good penetration ability and provide good sustained release while dual-layer MNs can regulate the amount of drug released, which could present an alternative for stem cell therapy.
Assuntos
Fibroínas , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Células Estromais , Células-Tronco , SedaRESUMO
Our previous study demonstrated that ultrasound is able to promote differentiation on neural stem cells (NSCs), and dual-frequency ultrasound promotes this effect due to enhanced acoustic cavitation compared with single-frequency ultrasound. However, the underlying biological reasons have not been well disclosed. The purpose of this study was to investigate the underlying bioeffects, mechanisms and signaling pathways of dual-frequency ultrasound on NSC differentiation. The morphology, neurite outgrowth, and differentiation percentages were investigated under various dual-frequency simulation parameters with exposure periods varying from 5 to 15 min. Morphological observations identified that dual-frequency ultrasound stimulation promoted ultrasound dose-dependent neurite outgrowth. In particular, cells exposed for 10 min/2 days showed optimal neurite outgrowth and neuron differentiation percentages. In addition, live cell calcium images showed that dual-frequency ultrasound enhanced the internal calcium content of the cells, and calcium ions entering cells from the extracellular environment could be observed. Dual frequency ultrasound exposure enhanced extracellular calcium influx and upregulated extracellular signal-regulated kinases 1/2 (ERK1/2) expression. Observations from immunostaining and protein expression examinations also identified that dual-frequency ultrasound promoted brain-derived neurotrophic factor (BDNF) secretion from astrocytes derived from NSCs. In summary, evidence supports that dual-frequency ultrasound effectively enhances functional neuron differentiation via calcium channel regulation via the downstream ERK1/2 pathway and promotes BDNF secretion to serve as feedback to cascade neuron differentiation. The results may provide an alternative for cell-based therapy in brain injury.
Assuntos
Diferenciação Celular , Sistema de Sinalização das MAP Quinases , Células-Tronco Neurais , Ondas Ultrassônicas , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cálcio/metabolismo , Células Cultivadas , Células-Tronco Neurais/citologia , Neurônios/citologia , Transdução de SinaisRESUMO
Emerging wearable electronics, wireless communication, and tissue engineering require the development of conductive fiber-shaped electrodes and biointerfaces. Ti3C2Tx MXene nanosheets serve as promising building block units for the construction of highly conductive fibers with integrated functionalities, yet a facile and scalable fabrication scheme is highly required. Herein, a cation-induced assembly process is developed for the scalable fabrication of conductive fibers with MXene sheaths and alginate cores (abbreviated as MXene@A). The fabrication scheme of MXene@A fibers includes the fast extrusion of alginate fibers followed by electrostatic assembly of MXene nanosheets, enabling high-speed fiber production. When multiple fabrication parameters are optimized, the MXene@A fibers exhibit a superior electrical conductivity of 1083 S cm-1, which can be integrated as Joule heaters into textiles for wearable thermal management. By triggering reversible de/hydration of alginate cores upon heating, the MXene@A fibers can be repeatedly contracted and generate large contraction stress that is >40 times higher than the ones of mammalian skeletal muscle. Furthermore, the MXene@A springs demonstrate large contraction strains up to 65.5% and are then fabricated into a reconfigurable dipole antenna to wirelessly monitor the surrounding heat sources. In the end, with the biocompatibility of MXene nanosheets, the MXene@A fibers enable the guidance of neural stem/progenitor cells differentiation and the promotion of neurite outgrowth. With a cation-induced assembly process, our multifunctional MXene@A fibers exhibit high scalability for future manufacturing and hold the prospect to inspire other applications.
Assuntos
Alginatos , Dispositivos Eletrônicos Vestíveis , Animais , Cátions , Diferenciação Celular , Comunicação , Condutividade Elétrica , MamíferosRESUMO
The features or actuation behaviors of nature's creatures provide concepts for the development of biomimetic soft bioactuators/robots with stimuli-responsive capabilities, design convenience, and environmental adaptivity in various fields. Mimosa pudica is a mechanically responsive plant that can convert pressure to the motion of leaves. When the leaves receive pressure, the occurrence of asymmetric turgor in the extensor and flexor sides of the pulvinus from redistributing the water in the pulvinus causes the bending of the pulvinus. Inspired by the actuation of Mimosa pudica, designing soft bioactuators can convert external stimulations to driving forces for the actuation of constructs which has been receiving increased attention and has potential applications in many fields. 4D printing technology has emerged as a new strategy for creating versatile soft bioactuators/robots by integrating printing technologies with stimuli-responsive materials. In this study, we developed a hybrid ink by combining gelatin methacryloyl (GelMA) polymers with iron oxide nanoparticles (IONs). This hybrid ION-GelMA ink exhibits tunable rheology, controllable mechanical properties, magnetic-responsive behaviors, and printability by integrating the internal metal ion-polymeric chain interactions and photo-crosslinking chemistries. This design offers the inks a dual crosslink mechanism combining the advantages of photocrosslinking and ionic crosslinking to rapidly form the construct within 60 s of UV exposure time. In addition, the magnetic-responsive actuation of ION-GelMA constructs can be regulated by different ION concentrations (0-10%). Furthermore, we used the ION-GelMA inks to fabricate a Mimosa pudica-like soft bioactuator through a mold casting method and a direct-ink-writing (DIW) printing technology. Obviously, the pinnule leaf structure of printed constructs presents a continuous reversible shape transformation in an air phase without any liquid as a medium, which can mimic the motion characteristics of natural creatures. At the same time, compared to the model casting process, the DIW printed bioactuators show a more refined and biomimetic transformation shape that closely resembles the movement of the pinnule leaf of Mimosa pudica in response to stimulation. Overall, this study indicates the proof of concept and the potential prospect of magnetic-responsive ION-GelMA inks for the rapid prototyping of biomimetic soft bioactuators/robots with untethered non-contact magneto-actuations.
RESUMO
Traumatic brain injury causes inflammation and glial scarring that impede brain tissue repair, so stimulating angiogenesis and recovery of brain function remain challenging. Here we present an adaptable conductive microporous hydrogel consisting of gold nanoyarn balls-coated injectable building blocks possessing interconnected pores to improve angiogenesis and recovery of brain function in traumatic brain injury. We show that following minimally invasive implantation, the adaptable hydrogel is able to fill defects with complex shapes and regulate the traumatic brain injury environment in a mouse model. We find that placement of this injectable hydrogel at peri-trauma regions enhances mature brain-derived neurotrophic factor by 180% and improves angiogenesis by 250% in vivo within 2 weeks after electromagnetized stimulation, and that these effects facilitate neuron survival and motor function recovery by 50%. We use blood oxygenation level-dependent functional neuroimaging to reveal the successful restoration of functional brain connectivity in the corticostriatal and corticolimbic circuits.
Assuntos
Lesões Encefálicas Traumáticas , Hidrogéis , Animais , Encéfalo , Lesões Encefálicas Traumáticas/terapia , Inflamação , Camundongos , Recuperação de Função FisiológicaRESUMO
Stem cell-based in vitro models may provide potential therapeutic strategies and allow drug screening for neurodegenerative diseases, including Alzheimer's disease (AD). Herein, we develop a neural stem cell (NSC) spheroid-based biochip that is characterized by a brain-like structure, well-defined neural differentiation, and neural network formation, representing a brain-on-a-chip. This system consisted of microelectrode arrays with a multichannel platform and allowed the real-time monitoring of network formation and degeneration by impedance analysis. The parameters of this platform for the real-time tracking of network development and organization were established based on our previous study. Subsequently, ß-amyloid (Aß) was added into the brain-on-a-chip system to generate an AD-on-a-chip model, and toxic effects on neurons and the degeneration of synapses were observed. The AD-on-a-chip model may help us to investigate the neurotoxicity of Aß on neurons and neural networks in real time. Aß causes neural damage and accumulates around neurites or inside neurospheroids, as observed by immunostaining and scanning electron microscopy (SEM). After incubation with Aß, reactive oxygen species (ROS) increased, synapse function decreased, and the neurotransmitter-acetylcholine (ACh) concentration decreased were observed. Most importantly, the real-time analysis system monitored the impedance value variation in the system with Aß incubation, providing consecutive network disconnection data that are consistent with biological data. This platform provides simple, real-time, and convenient sensing to monitor the network microenvironment. The proposed AD-on-a-chip model enhances the understanding of neurological pathology, and the development of this model provides an alternative for the study of drug discovery and cell-protein interactions in the brain.
RESUMO
Gut microbiota are involved in many physiological functions such as metabolism, brain development, and neurodegenerative diseases. Many microbes in the digestive tract do not maintain a constant level of their relative abundance but show daily oscillations under normal conditions. Recent evidence indicates that chronic jetlag, constant darkness, or deletion of the circadian core gene can alter the composition of gut microbiota and dampen the daily oscillation of gut microbes. However, the neuronal circuit responsible for modulating gut microbiota remained unclear. Using genetic mouse models and 16s rRNA metagenomic analysis, we find that light-dark cycle information transmitted by the intrinsically photosensitive retinal ganglion cells (ipRGCs) is essential for daily oscillations of gut microbes under temporal restricted high-fat diet conditions. Furthermore, aberrant light exposure such as dim light at night (dLAN) can alter the composition, relative abundance, and daily oscillations of gut microbiota. Together, our results indicate that external light-dark cycle information can modulate gut microbiota in the direction from the brain to the gut via the sensory system.
Assuntos
Microbioma Gastrointestinal , Células Ganglionares da Retina , Animais , Ritmo Circadiano , Luz , Camundongos , Fotoperíodo , RNA Ribossômico 16S/metabolismo , Células Ganglionares da Retina/metabolismo , Opsinas de Bastonetes/genética , Opsinas de Bastonetes/metabolismoRESUMO
Dissolving microneedles made from natural polymers recently have gained much attention as an efficient transdermal drug delivery system (TDDS). For the first time, ulvan, a sulfated polysaccharide extracted from Ulva lactuca, was applied to fabricate dissolving microneedles through a two-step casting method. The ulvan microneedles (UMNs) made from 4% ulvan solution were in a pyramidal shape with an average height of 655 µm and an aspect ratio of 2.63. The in vitro skin insertion study showed the UMNs could totally penetrate into the porcine skin to the dermis layer and rapidly dissolved as the needle height was reduced by 90.3% after post-insertion of only 2 min. The rapid dissolution of UMNs in situ thus could release the loaded model drugs of rhodamine 6G (R6G) and bovine serum albumin-fluorescein isothiocyanate conjugate (FITC-BSA) in the skin tissue. The in vitro drug release profiles through porcine skin revealed the UMNs markedly enhanced the cumulative release of FITC-BSA. In addition, the UMNs had good biocompatibility towards normal cells of HaCaT and NIH3T3. Briefly, this study demonstrates the rapidly dissolving UMNs could effectively carry the drug into skin and thus can be developed as a potential TDDS in the pharmaceutical and cosmeceutical fields.
Assuntos
Sistemas de Liberação de Medicamentos , Polissacarídeos , Administração Cutânea , Animais , Sistemas de Liberação de Medicamentos/métodos , Camundongos , Células NIH 3T3 , Preparações Farmacêuticas , Pele , SuínosRESUMO
Chronic kidney disease (CKD) is a systemic disorder that combines complex bone and mineral abnormalities. The high level of parathyroid hormone (PTH) in the blood causes irreversible renal dysfunction and cardiovascular disease. Therefore, it is necessary to reduce level of PTH in the blood of patients with uremic state. In this study, chitosan and heparin were chosen to form polysaccharide-based multilayer films based on their antibacterial ability, good biocompatibility and hemocompatibility. In addition, a previous study has revealed that PTH is a heparin/polyanion binding protein because of the similarity of heparin to the cell surface proteoglycans. Subsequently, the surface properties including thickness, surface hydrophobicity and surface charge of a series of multilayer films were analyzed. The PTH adsorption rate of a series of multilayer films was also assessed. The results revealed that the optimizing condition is (CHI/HEP)2.5 and 60 min in both PBS only and PBS with the addition of bovine serum albumin, which demonstrated the specific adsorption of PTH on the materials. Furthermore, the hemolysis test also revealed that (CHI/HEP)2.5 shows good blood compatibility. It is considered that polysaccharide-based multilayer films may provide an alternative for the surface modification of hemodialysis membranes and equipment.
RESUMO
Glioblastoma multiforme (GBM) is the most aggressive glioma. The treatment response is always low, and the condition is typically rapidly fatal. The undifferentiated and self-renewal characteristics of cancer stem cells (CSCs) have been reported, and their potential contribution may cause tumor initiation, recurrence, metastasis, and therapeutic resistance. In particular, glioblastoma stem-like cells exhibit highly invasive properties and drug resistance, serving as a model for the development of novel therapeutic strategies. Induction therapy provides an alternative therapeutic strategy to eliminate the stem cell properties of CSCs and enhance therapeutic sensitivity. The differentiated cells may lose their self-renewal ability, downregulate stem cell-related genes and drug resistance genes, and enhance anticancer drug sensitivity. Therefore, the purpose of this study is to establish a niche for glioblastoma stem-like cell selection as a platform and facilitate the assessment of differentiation therapy on GBM cancer stem-like colonies by retinoic acid (RA) with temozolomide (TMZ)-loaded gold nanoparticles (GNPs) associated with low-intensity ultrasound (LIUS). Herein, a hyaluronic acid-based material system was used to isolate GBM cancer stem-like colonies. Colony formation, size determination, stem cell-related marker expression, and GBM cancer stem-like cell marker expression with the culture period were identified. The effect of TMZ on GBM stem-like colonies on HA-based material systems was also determined, and the results revealed that drug resistance was highly enhanced in GBM colonies compared with that in the control cell population. In addition, GBM colonies also exhibited a significant increase in breast cancer resistance protein expression, which is consistent with the drug resistance effect. Furthermore, several factors, including LIUS, RA, and GNPs, were used to determine the possibility of induction therapy. RA with TMZ-loaded GNP-associated LIUS stimulation exhibited a significant and synergistic effect on the differentiation effect and drug sensitivity enhancement. The GBM cancer stem-like colony system presents an opportunity for the development of new therapeutic strategies, and this study provides an alternative differentiation therapy for malignant tumors.
Assuntos
Antineoplásicos/farmacologia , Portadores de Fármacos/química , Glioblastoma/tratamento farmacológico , Nanopartículas Metálicas/química , Temozolomida/farmacologia , Tretinoína/farmacologia , Antineoplásicos/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Ouro/química , Humanos , Ácido Hialurônico/química , Quimioterapia de Indução , Células-Tronco Neoplásicas/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Temozolomida/química , Tretinoína/química , Ondas UltrassônicasRESUMO
Stem cell-based approaches have become a promising therapeutic strategy for treating ischemic diseases. The aim of this study was to develop injectable hydrogel systems for the local release of stromal cell-derived factor-1α (SDF-1α) to recruit adipose stem cells (ASCs) that express CXCR4 to achieve stem cell therapy and therapeutic angiogenesis. Thermoresponsive and injectable chitosan (CS)/ß-glycerophosphate disodium salt pentahydrate (ßGP) hydrogels with different concentrations of hyaluronic acid (HA) were designed and fabricated to achieve local and sustained release of SDF-1α for ASC recruitment. Herein, the material structures, physical properties, gelation temperature, and gelation time of hydrogels with different compositions were determined. The incorporation of 0.9% HA in CS-based hydrogels not only enhanced the gelation time but also increased the strength of the hydrogels. In addition, the results revealed that the thermoresponsive and injectable CS/ßGP/HA hydrogels showed good biocompatibility. In addition, the in vitro release profiles showed that the hydrogels achieved sustained release of SDF-1α over 7 days and enhanced ASC migration. The results revealed that the hydrogels with HA enhanced the sustained release effect compared with the hydrogel without HA, indicating that the HA content regulated the physical and release properties of the injectable hydrogels. Therefore, thermoresponsive and injectable CS/ßGP/HA hydrogels may provide an alternative for treating ischemic diseases via SDF-1/CXCR4 axis for ASC recruitment and retention.
Assuntos
Quimiocina CXCL12/administração & dosagem , Quitosana/química , Preparações de Ação Retardada/química , Hidrogéis/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Receptores CXCR4/metabolismo , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CXCL12/farmacologia , Humanos , Injeções , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Receptores CXCR4/análise , Transdução de Sinais/efeitos dos fármacosRESUMO
Biosensors constitute selective, sensitive, and rapid tools for disease diagnosis in tissue engineering applications. Compared to standard enzyme-linked immunosorbent assay (ELISA) analytical technology, biosensors provide a strategy to real-time and on-site monitor micro biophysiological signals via a combination of biological, chemical, and physical technologies. This review summarizes the recent and significant advances made in various biosensor technologies for different applications of biological and biomedical interest, especially on tissue engineering applications. Different fabrication techniques utilized for tissue engineering purposes, such as computer numeric control (CNC), photolithographic, casting, and 3D printing technologies are also discussed. Key developments in the cell/tissue-based biosensors, biomolecular sensing strategies, and the expansion of several biochip approaches such as organs-on-chips, paper based-biochips, and flexible biosensors are available. Cell polarity and cell behaviors such as proliferation, differentiation, stimulation response, and metabolism detection are included. Biosensors for diagnosing tissue disease modes such as brain, heart, lung, and liver systems and for bioimaging are discussed. Finally, we discuss the challenges faced by current biosensing techniques and highlight future prospects of biosensors for tissue engineering applications.