Project description:Uncontrolled and excessive fibrosis after myocardial infarction (MI) in the peri-infarct zone leads to left ventricular remodeling and deterioration of cardiac function. Inhibiting fibroblast activation during the mature phase of cardiac repair improves cardiac remodeling and function after MI. Here, we engineered a biocompatible microneedle (MN) patch using gelatin methacryloyl and loaded it with galunisertib, a transforming growth factor-beta (TGF-β)-specific inhibitor, to treat excessive cardiac fibrosis after MI. The MN patch could sustainably release galunisertib for more than 2 weeks and provide mechanical support for the fragile ventricular wall. After being applied to a rat model of MI, the galunisertib-loaded MN patch improved long-term cardiac function and reduced cardiac fibrosis by effectively inhibiting TGF-β depending on fibroblast activation. This strategy shows the potential of the MN patch as an advanced platform to locally deliver direct antifibrotic drugs to prevent myocardial fibrosis for the treatment of MI and the promotion of cardiac repair.
Project description:Medical tattoos provide medical information, guide radiotherapy, and improve cosmetic outcomes of medical interventions. These tattoos are administered by repeated needle injection that causes pain, bleeding, and risk of infection, which limit more widespread use. Here, we developed single-use microneedle (MN) patches to deposit tattoos in the skin in a simple, rapid, painless, and bloodless way without biohazardous sharps waste. MN patch tattoos were designed with numbers, letters, symbols, environmentally responsive inks, and QR codes. Colored tattoos, and tattoos only visible with ultraviolet illumination for increased privacy, were developed and retained in the skin for at least one year. These MN patch tattoos recorded medical conditions such as diabetic medical alerts and vaccination status, responded to biophysical cues for possible physiological monitoring, and encoded complex personal health information. MN patches may increase safety and access to medical tattoos for improved fiducial marking, medical information storage, physiological monitoring, and cosmetic outcomes.
Project description:Microneedles are gaining a lot of attention in the context of sampling cutaneous biofluids such as capillary blood. Their minimal invasiveness and user-friendliness make them a prominent substitute for venous puncture or finger-pricking. Although the latter is suitable for self-sampling, the impracticality of manual handling and the difficulty of obtaining enough qualitative sample is driving the search for better solutions. In this context, hollow microneedle arrays (HMNAs) are particularly interesting for completely integrating sample-to-answer solutions as they create a duct between the skin and the sampling device. However, the fabrication of sharp-tipped HMNAs with a high aspect ratio (AR) is challenging, especially since a length of ≥1500 μm is desired to reach the blood capillaries. In this paper, we first described a novel two-step fabrication protocol for HMNAs in stainless steel by percussion laser drilling and subsequent micro-milling. The HMNAs were then integrated into a self-powered microfluidic sampling patch, containing a capillary pump which was optimized to generate negative pressure differences up to 40.9 ± 1.8 kPa. The sampling patch was validated in vitro, showing the feasibility of sampling 40 μL of liquid. It is anticipated that our proof-of-concept is a starting point for more sophisticated all-in-one biofluid sampling and point-of-care testing systems.
Project description:The skin is considered the largest and most accessible organ in the human body, and allows the use of noninvasive and efficient strategies for drug administration, such as the transdermal drug delivery system (TDDS). TDDSs are systems or patches, with the ability and purpose to deliver effective and therapeutic doses of drugs through the skin. Regarding the specific interaction between hydrogels (HG) and microneedles (MNs), we seek to find out how this combination would be applied in the context of drug delivery, and we detail some possible advantages of the methods used. Depending on the components belonging to the HG matrix, we can obtain some essential characteristics that make the combination of hydrogels-microneedles (HG-MNs) very advantageous, such as the response to external stimuli, among others. Based on multiple characteristics provided by HGMNs that are depicted in this work, it is possible to obtain unique properties that include controlled, sustained, and localized drug release, as well as the possibility of a synergistic association between the components of the formulation and the combination of more than one bioactive component. In conclusion, a system based on HG-MNs can offer many advantages in the biomedical field, bringing to light a new technological and safe system for improving the pharmacokinetics and pharmacodynamics of drugs and new treatment perspectives.
Project description:Rapid diagnostic tests are one of the most commonly used tests to detect and screen for infectious diseases in the developing world. While these tests are simple, inexpensive, and readily available, they rely on finger-prick blood sampling, which requires trained medical personnel, poses risks of infection, and can complicate cooperation in young children, asymptomatic individuals, and communities with blood taboos. Here, we report a novel microneedle-based skin patch for the rapid detection of protein biomarkers in dermal interstitial fluid. Sample collection is facilitated by a hydrophilic hollow microneedle array that autonomously extracts and transports interstitial fluid to an antibody-based lateral flow test strip via surface tension for colorimetric antigen detection. We employ a simple gold enhancement treatment to enhance the detection sensitivity of this colloidal gold-based lateral flow assay and elucidate the underlying mechanism of this enhancement mechanism through experimental investigation. For proof-of-concept, this device was used to detect Plasmodium falciparum histidine-rich protein 2, a biomarker for malaria infection, which could be detected at concentrations as low as 8 ng/mL. Each test can be completed in <20 min and requires no equipment. To the best of our knowledge, this work is the first demonstration of a microneedle-based lateral flow assay for rapid protein detection in dermal interstitial fluid. In addition to its simplicity, minimally invasive nature, and low cost, this diagnostic device can be readily adapted to detect other protein biomarkers in interstitial fluid, making it a promising tool for point-of-care testing.
Project description:Sleep monitoring is an important part of health management because sleep quality is crucial for restoration of human health. However, current commercial products of polysomnography are cumbersome with connecting wires and state-of-the-art flexible sensors are still interferential for being attached to the body. Herein, we develop a flexible-integrated multimodal sensing patch based on hydrogel and its application in unconstraint sleep monitoring. The patch comprises a bottom hydrogel-based dual-mode pressure-temperature sensing layer and a top electrospun nanofiber-based non-contact detection layer as one integrated device. The hydrogel as core substrate exhibits strong toughness and water retention, and the multimodal sensing of temperature, pressure, and non-contact proximity is realized based on different sensing mechanisms with no crosstalk interference. The multimodal sensing function is verified in a simulated real-world scenario by a robotic hand grasping objects to validate its practicability. Multiple multimodal sensing patches integrated on different locations of a pillow are assembled for intelligent sleep monitoring. Versatile human-pillow interaction information as well as their evolution over time are acquired and analyzed by a one-dimensional convolutional neural network. Track of head movement and recognition of bad patterns that may lead to poor sleep are achieved, which provides a promising approach for sleep monitoring.
Project description:Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement. Attempts in this area tend to develop new forms to make their applications more convenient and wider. Here, we propose a novel Chinese herb microneedle (CHMN) patch by integrating the herbal extracts, Premna microphylla and Centella asiatica, with microstructure of microneedle for wound healing. Such path is composed of sap extracted from the herbal leaves via traditional kneading method and solidified by plant ash derived from the brine induced process of tofu in a well-designed mold. Because the leaves of the Premna microphylla are rich in pectin and various amino acids, the CHMN could be imparted with medicinal efficacy of heat clearing, detoxicating, detumescence and hemostatic. Besides, with the excellent pharmaceutical activity of Asiatic acid extracted from Centella asiatica, the CHMN is potential in promoting relevant growth factor genes expression in fibroblasts and showing excellent performance in anti-oxidant, anti-inflammatory and anti-bacterial activity. Taking advantages of these pure herbal compositions, we have demonstrated that the derived CHMN was with dramatical achievement in anti-bacteria, inhibiting inflammatory, collagen deposition, angiogenesis and tissue reconstruction during the wound closure. These results indicate that the integration of traditional Chinese herbs with progressive technologies will facilitate the development and promotion of traditional Chinese medicine in modern society.
Project description:Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.
Project description:Microneedle sensor technology offers exciting opportunities for decentralized clinical analyses. A novel issue puts forward herein is to demonstrate the uniqueness of membrane-based microneedles to accomplish real-time, on-body monitoring of multiple ions simultaneously. The use of multi-ion detection is clinically relevant since it is expected to provide a more complete and reliable assessment of the clinical status of a subject concerning electrolyte disorders and others. We present a microneedle system for transdermal multiplexed tracing of pH, Na+, K+, Ca2+, Li+, and Cl-. The device consists of an array of seven solid microneedles externally modified to provide six indicator electrodes, each selective for a different ion, and a common reference electrode, all integrated into a wearable patch read in a potentiometric mode. We show in vitro measurements at the expected clinical levels, resulting in a fast response time, excellent reversibility and repeatability, and adequate selectivity. Close-to-Nernstian sensitivity, sufficient stability and resiliency to skin penetration guarantee the sensor's success in transdermal measurements, which we demonstrate through ex vivo (with pieces of rat skin) and in vivo (on-body measurements in rats) tests. Accuracy is evaluated by comparison with gold standard techniques to characterize collected dermal fluid, blood, and serum. In the past, interstitial fluid (ISF) analysis has been challenging due to difficult sample collection and analysis. For ions, this has resulted in extrapolations from blood concentrations (invasive tests) rather than pure measurements in ISF. The developed microneedle patch is a relevant analytical tool to address this information gap.
Project description:Nitric oxide synthase 3 (NOS3) eluting polyvinyl alcohol-based hydrogels have a large potential in medical applications and device coatings. NOS3 promotes nitric oxide and nitrate production and can effectively be delivered using insect cell viruses, termed baculoviruses. Nitric oxide is known for regulating cell proliferation, promoting blood vessel vasodilation, and inhibiting bacterial growth. The polyvinyl alcohol (PVA)-based hydrogels investigated here sustained baculovirus elution from five to 25 days, depending on the hydrogel composition. The quantity of viable baculovirus loaded significantly declined with each freeze-thaw from one to four (15.3 ± 2.9% vs. 0.9 ± 0.5%, respectively). The addition of gelatin to the hydrogels protected baculovirus viability during the freeze-thaw cycles, resulting in a loading capacity of 94.6 ± 1.2% with sustained elution over 23 days. Adding chitosan, PEG-8000, and gelatin to the hydrogels altered the properties of the hydrogel, including swelling, blood coagulation, and antimicrobial effects, beneficial for different therapeutic applications. Passive absorption of the baculovirus into PVA hydrogels exhibited the highest baculovirus loading (96.4 ± 0.6%) with elution over 25 days. The baculovirus-eluting hydrogels were hemocompatible and non-cytotoxic, with no cell proliferation or viability reduction after incubation. This PVA delivery system provides a method for high loading and sustained release of baculoviruses, sustaining nitric oxide gene delivery. This proof of concept has clinical applications as a medical device or stent coating by delivering therapeutic genes, improving blood compatibility, preventing thrombosis, and preventing infection.