ABSTRACT
BACKGROUND: Newcastle disease (ND) poses significant challenges within the poultry industry, leading to increased mortality rates, compromised growth, weakened immunity and elevated levels of inflammation. OBJECTIVE: This study explores the potential of dietary arginine supplementation to ameliorate these adverse effects of ND, leveraging arginine's well-documented benefits in enhancing growth and immune responses. METHODS: A total of 480 one-day-old male broiler chicks were meticulously categorised into eight groups, encompassing both infected and noninfected cohorts. These chicks received diets with arginine levels at 85%, 100%, 125% and 150% of recommended standards. The study entailed a comprehensive examination of clinical manifestations, growth performance metrics, haemagglutination inhibition (HI) test results, and serum concentrations of proinflammatory cytokines, adrenocorticotropic hormone (ACTH), and cortisol (CORT). RESULTS: The infection significantly curtailed feed consumption (p = 0.0001) and weight gain (p = 0.0001) while concurrently depressing HI titres. Additionally, infected chicks experienced an exacerbated feed conversion ratio (p = 0.0001), escalated mortality rates (p = 0.0001), and elevated serum concentrations of proinflammatory cytokines (p = 0.0001), ACTH (p = 0.0001), and CORT (p = 0.0001). Remarkably, dietary arginine supplementation effectively mitigated the adverse impacts of ND infection on growth, immune responses and proinflammatory cytokine levels. In the context of ND infection, mortality rates and inflammation surge, while growth and immunity are significantly compromised. CONCLUSIONS: The strategic inclusion of arginine in the diet emerges as a potent strategy to counteract the deleterious effects of ND. Supplementation with arginine at levels exceeding the conventional dietary recommendations is recommended to alleviate the detrimental consequences of ND effectively.
Subject(s)
Animal Feed , Arginine , Chickens , Diet , Dietary Supplements , Newcastle Disease , Newcastle disease virus , Poultry Diseases , Animals , Arginine/administration & dosage , Dietary Supplements/analysis , Newcastle Disease/prevention & control , Diet/veterinary , Male , Animal Feed/analysis , Newcastle disease virus/immunology , Poultry Diseases/prevention & control , Poultry Diseases/virologyABSTRACT
Theranostic sutures are derived from innovative ideas to enhance wound healing results by adding wound diagnostics and therapeutics to typical sutures by functionalizing them with additional materials. Here, we present a new direct electrospinning method for the fast, continuous, inexpensive, and high-throughput production of versatile nanofibrous-coated suture threads, with precise control over various essential microstructural and physical characteristics. The thickness of the coating layer and the alignment of nanofibers with the thread's direction can be adjusted by the user by varying the spooling speed and the displacement between the spinneret needle and thread. To show the flexibility of our method for a range of different materials selected, gelatin, polycaprolactone, silk fibroin, and PEDOT:PSS (poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate)) were the resultant nanofibers characterized by scanning electron microscopy (SEM) imaging and conductivity tests. In a series of in vitro and ex vivo tests (pig skin), sutures were successfully tested for their flexibility and mechanical properties when used as weaving and knotting sutures, and their biocompatibility with a keratinocyte cell line. For temperature-based drug-releasing tests, two fluorescent molecules as drug models with high and low molecular weight, namely fluorescein isothiocyanate-dextran (20 kDa) and rhodamine B (470 Da), were used, and their steady release with incremental increase of temperature to 37 °C over 120 min was seen, which is appropriate for bacterial treatment drugs. Given the advantages of the presented technique, it seems to have promising potential to be used in future medical applications for wound closure and bacterial infection treatment via a temperature-triggered drug release strategy.
ABSTRACT
The present work aims to develop optimized scaffolds for bone repair by incorporating mesoporous nanoparticles into them, thereby combining bioactive factors for cell growth and preventing rapid release or loss of effectiveness. We synthesized biocompatible and biodegradable scaffolds designed for the controlled codelivery of curcumin (CUR) and recombinant human bone morphogenic protein-2 (rhBMP-2). Active agents in dendritic silica/titania mesoporous nanoparticles (DSTNs) were incorporated at different weight percentages (0, 2, 5, 7, 9, and 10 wt %) into a matrix of polycaprolactone (PCL) and polyethylene glycol (PEG) nanofibers, forming the CUR-BMP-2@DSTNs/PCL-PEG delivery system (S0, S2, S5, S7, S9, and S10, respectively, with the number showing the weight percentage). To enhance the formation process, the system was treated using low-intensity pulsed ultrasound (LIPUS). Different advanced methods were employed to assess the physical, chemical, and mechanical characteristics of the fabricated scaffolds, all confirming that incorporating the nanoparticles improves their mechanical and structural properties. Their hydrophilicity increased by approximately 25%, leading to ca. 53% enhancement in their water absorption capacity. Furthermore, we observed a sustained release of approximately 97% for CUR and 70% for BMP-2 for the S7 (scaffold with 7 wt % DSTNs) over 28 days, which was further enhanced using ultrasound. In vitro studies demonstrated accelerated scaffold biodegradation, with the highest level observed in S7 scaffolds, approximately three times higher than the control group. Moreover, the cell viability and proliferation on DSTNs-containing scaffolds increased when compared to the control group. Overall, our study presents a promising nanocomposite scaffold design with notable improvements in structural, mechanical, and biological properties compared to the control group, along with controlled and sustained drug release capabilities. This makes the scaffold a compelling candidate for advanced bone tissue engineering and regenerative therapies.
Subject(s)
Biocompatible Materials , Bone Morphogenetic Protein 2 , Materials Testing , Nanofibers , Osteogenesis , Particle Size , Osteogenesis/drug effects , Nanofibers/chemistry , Bone Morphogenetic Protein 2/chemistry , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Ultrasonic Waves , Curcumin/chemistry , Curcumin/pharmacology , Cell Proliferation/drug effects , Recombinant Proteins/chemistry , Recombinant Proteins/pharmacology , Recombinant Proteins/administration & dosage , Cell Survival/drug effects , Polyesters/chemistry , Polymers/chemistry , Tissue Scaffolds/chemistry , Polyethylene Glycols/chemistry , Transforming Growth Factor betaABSTRACT
Sorghum is a promising treatment for Alzheimer's disease (AD), due to its rich antioxidant and anti-inflammatory qualities. Fermentation may also affect nutritional values. Therefore, the purpose of this study was to discover the phenolic and flavonoid chemicals found in both fermented and non-fermented red sorghum, as well as their potential therapeutic uses for AD. L. fermentum, and L. reuteri, and/or L. plantarum and L. casei were used to ferment samples of sorghum. The rats were grouped into five groups, healthy animals, and rats with Alzheimer's receiving 200 mg/kg of saline, non-fermented sorghum, and fermented sorghum fermented with L. fermentum and L. reuteri, as well as L. plantarum and L. casei. Various assessments were conducted, including evaluations of behavioral responses, antioxidant responses, inflammatory responses, acetylcholine levels and acetylcholine esterase, and bacterial populations in stool. P-hydroxybenzoic acid, eriodictyo naringenin, and apigenin were significantly higher in fermented samples, while glycerols were higher in non-fermented samples. The induction of Alzheimer's led to decrease step-through latency, time in target zone, FRAP, acetylcholine levels, Bifidobacterium population and lactobacillus population, while increased escape latency, platform location latency, MDA levels, IL-6, TNF-α, acetylcholine esterase, and coliform population (P = 0.001). The administration of both non-fermented sorghum and fermented sorghum demonstrated the potential to reverse the effects of AD, with a notably higher efficacy observed in the fermented samples compared to the non-fermented ones. In conclusion, fermentation exerted significant effects on the bioactive compounds the administration of fermented sorghum resulted in improved behavioral responses, characterized by a reduction in oxidation, inflammation and microbial population.
Subject(s)
Alzheimer Disease , Antioxidants , Fermentation , Sorghum , Alzheimer Disease/microbiology , Alzheimer Disease/metabolism , Animals , Male , Rats , Rats, Wistar , Flavanones , Gastrointestinal Microbiome , Disease Models, Animal , Flavonoids , Apigenin/pharmacology , Phenols , Acetylcholine/metabolism , Acetylcholinesterase/metabolism , Anti-Inflammatory Agents/pharmacology , Lactobacillus , Plant Extracts/pharmacology , Feces/microbiology , Feces/chemistryABSTRACT
Remote health monitoring and treatment serve as critical drivers for advancing health equity, bridging geographical and socioeconomic disparities, ensuring equitable access to quality healthcare for those in underserved or remote regions. By democratizing healthcare, this approach offers timely interventions, continuous monitoring, and personalized care independent of one's location or socioeconomic status, thereby striving for an equitable distribution of health resources and outcomes. Meanwhile, microneedle arrays (MNAs), revolutionize painless and minimally invasive access to interstitial fluid for drug delivery and diagnostics. This paper introduces an integrated theranostic MNA system employing an array of colorimetric sensors to quantitatively measure -pH, glucose, and lactate, alongside a remotely-triggered system enabling on-demand drug delivery. Integration of an ultrasonic atomizer streamlines the drug delivery, facilitating rapid, pumpless, and point-of-care drug delivery, enhancing system portability while reducing complexities. An accompanying smartphone application interfaces the sensing and drug delivery components. Demonstrated capabilities include detecting pH (3 to 8), glucose (up to 16 mm), and lactate (up to 1.6 mm), showcasing on-demand drug delivery, and assessing delivery system performance via a scratch assay. This innovative approach confronts drug delivery challenges, particularly in managing chronic diseases requiring long-term treatment, while also offering avenues for non-invasive health monitoring through microneedle-based sensors.
ABSTRACT
Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that has limited treatment options. Current standard therapies, including surgery followed by radiotherapy and chemotherapy, are not very effective due to the rapid progression and recurrence of the tumor. Therefore, there is an urgent need for more effective treatments, such as combination therapy and localized drug delivery systems that can reduce systemic side effects. Recently, a handheld printer was developed that can deliver drugs directly to the tumor site. In this study, the feasibility of using this technology for localized co-delivery of temozolomide (TMZ) and deferiprone (DFP) to treat glioblastoma is showcased. A flexible drug-loaded mesh (GlioMesh) loaded with poly (lactic-co-glycolic acid) (PLGA) microparticles is printed, which shows the sustained release of both drugs for up to a month. The effectiveness of the printed drug-eluting mesh in terms of tumor toxicity and invasion inhibition is evaluated using a 3D micro-physiological system on a plate and the formation of GBM tumoroids within the microenvironment. The proposed in vitro model can identify the effective combination doses of TMZ and DFP in a sustained drug delivery platform. Additionally, our approach shows promise in GB therapy by enabling localized delivery of multiple drugs, preventing off-target cytotoxic effects.
Subject(s)
Glioblastoma , Humans , Glioblastoma/drug therapy , Glioblastoma/pathology , Hydrogels/therapeutic use , Drug Liberation , Temozolomide/therapeutic use , Printing, Three-Dimensional , Tumor MicroenvironmentABSTRACT
Flexible and multifunctional electronic devices and soft robots inspired by human organs, such as skin, have many applications. However, the emergence of electronic skins (e-skins) or textiles in biomedical engineering has made a great revolution in a myriad of people's lives who suffer from different types of diseases and problems in which their skin and muscles lose their appropriate functions. In this review, recent advances in the sensory function of the e-skins are described. Furthermore, we have categorized them from the sensory function perspective and highlighted their advantages and limitations. The categories are tactile sensors (including capacitive, piezoresistive, piezoelectric, triboelectric, and optical), temperature, and multi-sensors. In addition, we summarized the most recent advancements in sensors and their particular features. The role of material selection and structure in sensory function and other features of the e-skins are also discussed. Finally, current challenges and future prospects of these systems towards advanced biomedical applications are elaborated.
Subject(s)
Robotics , Wearable Electronic Devices , Humans , Skin , Textiles , Biomedical EngineeringABSTRACT
As miniaturized and simplified stem cell-derived 3D organ-like structures, organoids are rapidly emerging as powerful tools for biomedical applications. With their potential for personalized therapeutic interventions and high-throughput drug screening, organoids have gained significant attention recently. In this review, we discuss the latest developments in engineering organoids and using materials engineering, biochemical modifications, and advanced manufacturing technologies to improve organoid culture and replicate vital anatomical structures and functions of human tissues. We then explore the diverse biomedical applications of organoids, including drug development and disease modeling, and highlight the tools and analytical techniques used to investigate organoids and their microenvironments. We also examine the latest clinical trials and patents related to organoids that show promise for future clinical translation. Finally, we discuss the challenges and future perspectives of using organoids to advance biomedical research and potentially transform personalized medicine.
Subject(s)
Biomedical Research , Organoids , Humans , Stem Cells , Precision Medicine/methods , Biomedical Research/methods , Drug DevelopmentABSTRACT
The field of cancer immunotherapy has shown significant growth, and researchers are now focusing on effective strategies to enhance and prolong local immunomodulation. Injectable hydrogels (IHs) have emerged as versatile platforms for encapsulating and controlling the release of small molecules and cells, drawing significant attention for their potential to enhance antitumor immune responses while inhibiting metastasis and recurrence. IHs delivering natural killer (NK) cells, T cells, and antigen-presenting cells (APCs) offer a viable method for treating cancer. Indeed, it can bypass the extracellular matrix and gradually release small molecules or cells into the tumor microenvironment, thereby boosting immune responses against cancer cells. This review provides an overview of the recent advancements in cancer immunotherapy using IHs for delivering NK cells, T cells, APCs, chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. First, we introduce IHs as a delivery matrix, then summarize their applications for the local delivery of small molecules and immune cells to elicit robust anticancer immune responses. Additionally, we discuss recent progress in IHs systems used for local combination therapy, including chemoimmunotherapy, radio-immunotherapy, photothermal-immunotherapy, photodynamic-immunotherapy, and gene-immunotherapy. By comprehensively examining the utilization of IHs in cancer immunotherapy, this review aims to highlight the potential of IHs as effective carriers for immunotherapy delivery, facilitating the development of innovative strategies for cancer treatment. In addition, we demonstrate that using hydrogel-based platforms for the targeted delivery of immune cells, such as NK cells, T cells, and dendritic cells (DCs), has remarkable potential in cancer therapy. These innovative approaches have yielded substantial reductions in tumor growth, showcasing the ability of hydrogels to enhance the efficacy of immune-based treatments. STATEMENT OF SIGNIFICANCE: As cancer immunotherapy continues to expand, the mode of therapeutic agent delivery becomes increasingly critical. This review spotlights the forward-looking progress of IHs, emphasizing their potential to revolutionize localized immunotherapy delivery. By efficiently encapsulating and controlling the release of essential immune components such as T cells, NK cells, APCs, and various therapeutic agents, IHs offer a pioneering pathway to amplify immune reactions, moderate metastasis, and reduce recurrence. Their adaptability further shines when considering their role in emerging combination therapies, including chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. Understanding IHs' significance in cancer therapy is essential, suggesting a shift in cancer treatment dynamics and heralding a novel period of focused, enduring, and powerful therapeutic strategies.
Subject(s)
Hydrogels , Neoplasms , Humans , Hydrogels/therapeutic use , Immunotherapy/methods , Neoplasms/pathology , T-Lymphocytes , Combined Modality Therapy , Tumor MicroenvironmentABSTRACT
Systemically administered chemotherapy reduces the efficiency of the anticancer agent at the target tumor tissue and results in distributed drug to non-target organs, inducing negative side effects commonly associated with chemotherapy and necessitating repeated administration. Injectable hydrogels present themselves as a potential platform for non-invasive local delivery vehicles that can serve as a slow-releasing drug depot that fills tumor vasculature, tissue, or resection cavities. Herein, we have systematically formulated and tested an injectable shear-thinning hydrogel (STH) with a highly manipulable release profile for delivering doxorubicin, a common chemotherapeutic. By detailed characterization of the STH physical properties and degradation and release dynamics, we selected top candidates for testing in cancer models of increasing biomimicry. Two-dimensional cell culture, tumor-on-a-chip, and small animal models were used to demonstrate the high anticancer potential and reduced systemic toxicity of the STH that exhibits long-term (up to 80 days) doxorubicin release profiles for treatment of breast cancer and glioblastoma. The drug-loaded STH injected into tumor tissue was shown to increase overall survival in breast tumor- and glioblastoma-bearing animal models by 50% for 22 days and 25% for 52 days, respectively, showing high potential for localized, less frequent treatment of oncologic disease with reduced dosage requirements.
ABSTRACT
Glioblastoma multiform (GBM) tumor progression has been recognized to be correlated with extracellular matrix (ECM) stiffness. Dynamic variation of tumor ECM is primarily regulated by a family of enzymes which induce remodeling and degradation. In this paper, we investigated the effect of matrix stiffness on the invasion pattern of human glioblastoma tumoroids. A 3D-printed tumor-on-a-chip platform was utilized to culture human glioblastoma tumoroids with the capability of evaluating the effect of stiffness on tumor progression. To induce variations in the stiffness of the collagen matrix, different concentrations of collagenase were added, thereby creating an inhomogeneous collagen concentration. To better understand the mechanisms involved in GBM invasion, an in silico hybrid mathematical model was used to predict the evolution of a tumor in an inhomogeneous environment, providing the ability to study multiple dynamic interacting variables. The model consists of a continuum reaction-diffusion model for the growth of tumoroids and a discrete model to capture the migration of single cells into the surrounding tissue. Results revealed that tumoroids exhibit two distinct patterns of invasion in response to the concentration of collagenase, namely ring-type and finger-type patterns. Moreover, higher concentrations of collagenase resulted in greater invasion lengths, confirming the strong dependency of tumor behavior on the stiffness of the surrounding matrix. The agreement between the experimental results and the model's predictions demonstrates the advantages of this approach in investigating the impact of various extracellular matrix characteristics on tumor growth and invasion.
ABSTRACT
Hydrogels, a class of materials with a 3D network structure, are widely used in various applications of therapeutic delivery, particularly cancer therapy. Micro and nanogels as miniaturized structures of the bioengineered hydrogels may provide extensive benefits over the common hydrogels in encapsulation and controlled release of small molecular drugs, macromolecular therapeutics, and even cells. Cancer immunotherapy is rapidly developing, and micro/nanostructured hydrogels have gained wide attention regarding their engineered payload release properties that enhance systemic anticancer immunity. Additionally, they are a great candidate due to their local administration properties with a focus on local immune cell manipulation in favor of active and passive immunotherapies. Although applied locally, such micro/nanostructured can also activate systemic antitumor immune responses by releasing nanovaccines safely and effectively inhibiting tumor metastasis and recurrence. However, such hydrogels are mostly used as locally administered carriers to stimulate the immune cells by releasing tumor lysate, drugs, or nanovaccines. In this review, the latest developments in cancer immunotherapy are summarized using micro/nanostructured hydrogels with a particular emphasis on their function depending on the administration route. Moreover, the potential for clinical translation of these hydrogel-based cancer immunotherapies is also discussed.
Subject(s)
Hydrogels , Neoplasms , Humans , Hydrogels/chemistry , Drug Delivery Systems , Nanogels , Neoplasms/drug therapy , ImmunotherapyABSTRACT
Polymeric nanomaterials, nanogels, and solid nanoparticles can be fabricated using single or double emulsion methods. These materials hold great promise for various biomedical applications due to their biocompatibility, biodegradability, and their ability to control interactions with body fluids and cells. Despite the increasing use of nanoparticles in biomedicine and the plethora of publications on the topic, the biological behavior and efficacy of polymeric nanoparticles (PNPs) have not been as extensively studied as those of other nanoparticles. The gap between the potential of PNPs and their applications can mainly be attributed to the incomplete understanding of their biological identity. Under physiological conditions, such as specific temperatures and adequate protein concentrations, PNPs become coated with a "protein corona" (PC), rendering them potent tools for proteomics studies. In this review, we initially investigate the synthesis routes and chemical composition of conventional PNPs to better comprehend how they interact with proteins. Subsequently, we comprehensively explore the effects of material and biological parameters on the interactions between nanoparticles and proteins, encompassing reactions such as hydrophobic bonding and electrostatic interactions. Moreover, we delve into recent advances in PNP-based models that can be applied to nanoproteomics, discussing the new opportunities they offer for the clinical translation of nanoparticles and early prediction of diseases. By addressing these essential aspects, we aim to shed light on the potential of polymeric nanoparticles for biomedical applications and foster further research in this critical area.
ABSTRACT
Targeting different pathways in combinational therapy may lead to synergistic effects with higher drug efficiency. Due to a large number of candidate drugs and the variability in the genomic landscape of the disease, conventional cell culture models have limited success. Three-dimensional (3D) cell culture platforms such as tumoroids not only provide a pathophysiological relevant condition but also allow for low-cost and high-throughput drug screening strategies. Immunostaining of targeted proteins within a tumoroid is challenging as the interior cells are difficult to access via a non-destructive method. Immunohistochemistry (IHC) is an important technique in clinical research to explore the expression of various biomarkers. IHC staining of tumoroids allows non-destructive detection of unstable proteins by direct fixation of cells at the state of tumor microenvironment (TME) context, providing two main advantages. First, the target protein can be fixed without dissociating cells and disintegration of tumoroids into a single-cell suspension. Second, staining the preserved structure of tumoroids helps identify the location of the target proteins as well as the spatial distribution throughout the tumoroid geometry. In this protocol, we describe the detailed methodology of a non-destructive IHC staining of cancer biomarkers which minimizes the manipulation of tumoroids prior to fixation by eliminating multiple centrifugations and shaking steps typically required for removing excess hydrogel and collecting tumoroids. The protocol can be used in studies involving prognostic and predictive biomarker investigations in new anti-tumor drug development strategies.
ABSTRACT
Microneedle arrays (MNAs) are emerging devices that are mainly used for drug delivery and diagnostic applications through the skin. Different methods have been used to fabricate MNAs. Recently developed fabrication methods based on 3D printing have many advantages compared to conventional fabrication methods, such as faster fabrication in one step and the ability to fabricate complex structures with precise control over their geometry, form, size, and mechanical and biological properties. Despite the several advantages that 3D printing offers for the fabrication of microneedles, their poor penetration capability into the skin should be improved. MNAs need a sharp needle tip to penetrate the skin barrier layer, the stratum corneum (SC). This article presents a method to improve the penetration of 3D-printed microneedle arrays by investigating the effect of the printing angle on the penetration force of MNAs. The penetration force needed to puncture the skin for MNAs fabricated using a commercial digital light processing (DLP) printer, with different printing tilt angles (0-60°), was measured in this study. The results showed that the minimum puncture force was achieved using a 45° printing tilt angle. Using this angle, the puncture force was reduced by 38% compared to MNAs printed with a tilting angle of 0°. We also identified that a tip angle of 120° resulted in the smallest penetration force needed to puncture the skin. The outcomes of the research show that the presented method can significantly improve the penetration capability of 3D-printed MNAs into the skin.
ABSTRACT
Current treatment strategies for glioblastoma (GBM) including surgical resection and adjuvant radio/chemotherapy result in a limited progression-free survival time of patients due to rapidly occurring tumor recurrences. The urgent need for more effective treatments has led to the development of different approaches for localized drug delivery systems (DDSs) offering the advantages of reduced systemic side effects. A promising candidate for the treatment of GBMs is AT101, the R-(-)-enantiomer of gossypol due to its ability to induce apoptosis or trigger autophagic cell death in tumor cells. Here, we present an alginate-based drug-releasing mesh ladened with AT101-loaded PLGA microspheres (AT101-GlioMesh). The AT101-loaded PLGA microspheres were fabricated using an oil-in-water emulsion solvent evaporation method obtaining a high encapsulation efficiency. The drug-loaded microspheres enabled the release of AT101 over several days at the tumor site. The cytotoxic effect of the AT101-loaded mesh was evaluated using two different GBM cell lines. Strikingly, encapsulation of AT101 in PLGA-microparticles and subsequent embedding in GlioMesh resulted in a sustained delivery and more efficient cytotoxic effect of AT101 on both GBM cell lines. Thus, such a DDS holds promise for GBM therapy likely by preventing the development of tumor recurrences.
Subject(s)
Antineoplastic Agents , Glioblastoma , Gossypol , Humans , Glioblastoma/drug therapy , Glioblastoma/metabolism , Gossypol/pharmacology , Gossypol/therapeutic use , Surgical Mesh , Drug Delivery Systems/methods , MicrospheresABSTRACT
In situbioprinting-the process of depositing bioinks at a defected area, has recently emerged as a versatile technology for tissue repair and restorationviasite-specific delivery of pro-healing constructs. The ability to print multiple materialsin situis an exciting approach that allows simultaneous or sequential dispensing of different materials and cells to achieve tissue biomimicry. Herein, we report a modular handheld bioprinter that deposits a variety of bioinksin situwith exquisite control over their physical and chemical properties. Combined stereolithography 3D printing and microfluidic technologies allowed us to develop a novel low-priced handheld bioprinter. The ergonomic design of the handheld bioprinter facilitate the shape-controlled biofabrication of multi-component fibers with different cross-sectional shapes and material compositions. Furthermore, the capabilities of the produced fibers in the local delivery of therapeutic agents was demonstrated by incorporating drug-loaded microcarriers, extending the application of the printed fibers to on-demand, temporal, and dosage-control drug delivery platforms. Also, the versatility of this platform to produce biosensors and wearable electronics was demonstrated via incorporating conductive materials and integrating pH-responsive dyes. The handheld printer's efficacy in generating cell-laden fibers with high cell viability for site-specific cell delivery was shown by producing single-component and multi-component cell-laden fibers. In particular, the multi-component fibers were able to model the invasion of cancer cells into the adjacent tissue.
Subject(s)
Bioprinting , Tissue Scaffolds , Tissue Scaffolds/chemistry , Printing, Three-Dimensional , Microfluidics , Cell Survival , Tissue Engineering , HydrogelsABSTRACT
Managing slow-healing wounds and associated complications is challenging, time-consuming, and expensive. Systematic collection, analysis, and dissemination of correct wound status data are critical for enhancing healing outcomes and reducing complications. However, traditional data collection approaches are often neither accurate nor user-friendly and require diverse skill levels, resulting in the collection of inconsistent and unreliable data. As an advancement to the authors' previously developed hydrogel-based smart wound dressing, here is reported an enhanced integration of drug delivery and sensing (pH and glucose) modules for accelerated treatment and continuous monitoring of cutaneous wounds. In the current study, growth factor delivery modules and an array of colorimetric glucose sensors are incorporated into the dressing to promote wound healing and extend the dressing's utility for diabetic wound treatment. Furthermore, the efficacy of the wound dressing in monitoring infection and supporting wound healing via antibiotic and growth factor delivery is investigated in mice models. The updated dressing reveals excellent healing benefits on non-infected and infected wounds, as well as real-time monitoring and early detection of wound infection.
Subject(s)
Bandages , Soft Tissue Injuries , Surgical Wound Infection , Animals , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Soft Tissue Injuries/therapy , Surgical Wound Infection/therapyABSTRACT
Skin-interfaced electronics (skintronics) have received considerable attention due to their thinness, skin-like mechanical softness, excellent conformability, and multifunctional integration. Current advancements in skintronics have enabled health monitoring and digital medicine. Particularly, skintronics offer a personalized platform for early-stage disease diagnosis and treatment. In this comprehensive review, we discuss (1) the state-of-the-art skintronic devices, (2) material selections and platform considerations of future skintronics toward intelligent healthcare, (3) device fabrication and system integrations of skintronics, (4) an overview of the skintronic platform for personalized healthcare applications, including biosensing as well as wound healing, sleep monitoring, the assessment of SARS-CoV-2, and the augmented reality-/virtual reality-enhanced human-machine interfaces, and (5) current challenges and future opportunities of skintronics and their potentials in clinical translation and commercialization. The field of skintronics will not only minimize physical and physiological mismatches with the skin but also shift the paradigm in intelligent and personalized healthcare and offer unprecedented promise to revolutionize conventional medical practices.
Subject(s)
COVID-19 , Wearable Electronic Devices , Humans , SARS-CoV-2 , Electronics , Delivery of Health CareABSTRACT
To treat and manage chronic diseases, it is necessary to continuously monitor relevant biomarkers and modify treatment as the disease state changes. Compared to other bodily fluids, interstitial skin fluid (ISF) is a good choice for identifying biomarkers because it has a molecular composition most similar to blood plasma. Herein, a microneedle array (MNA) is presented to extract ISF painlessly and bloodlessly. The MNA is made of crosslinked poly(ethylene glycol) diacrylate (PEGDA), and an optimal balance of mechanical properties and absorption capability is suggested. Besides, the effect of needles' cross-section shape on skin penetration is studied. The MNA is integrated with a multiplexed sensor that provides a color change in a biomarker concentration-dependent manner based on the relevant reactions for colorimetric detection of pH and glucose biomarkers. The developed device enables diagnosis by visual inspection or quantitative red, green, and blue (RGB) analysis. The outcomes of this study show that MNA can successfully identify biomarkers in interstitial skin fluid in a matter of minutes. The home-based long-term monitoring and management of metabolic diseases will benefit from such practical and self-administrable biomarker detection.