Living organisms share the ability to grow various microstructures on their surface to achieve functions. Here we present a force stamp method to grow microstructures on the surface of hydrogels ...based on a force-triggered polymerisation mechanism of double-network hydrogels. This method allows fast spatial modulation of the morphology and chemistry of the hydrogel surface within seconds for on-demand functions. We demonstrate the oriented growth of cells and directional transportation of water droplets on the engineered hydrogel surfaces. This force-triggered method to chemically engineer the hydrogel surfaces provides a new tool in addition to the conventional methods using light or heat, and will promote the wide application of hydrogels in various fields.
Heart failure represents a primary cause of hospitalization and mortality in both developed and developing countries, often necessitating heart transplantation as the only viable recovery path. ...Despite advances in transplantation medicine, organ rejection remains a significant post-operative challenge, traditionally monitored through invasive endomyocardial biopsies (EMB). This study introduces a rapid prototyping approach to organ rejection monitoring via a sensor-integrated flexible patch, employing electrical impedance spectroscopy (EIS) for the non-invasive, continuous assessment of resistive and capacitive changes indicative of tissue rejection processes. Utilizing titanium-dioxide-coated electrodes for contactless impedance sensing, this method aims to mitigate the limitations associated with EMB, including procedural risks and the psychological burden on patients. The biosensor's design features, including electrode passivation and three-dimensional microelectrode protrusions, facilitate effective monitoring of cardiac rejection by aligning with the heart's curvature and responding to muscle contractions. Evaluation of sensor performance utilized SPICE simulations, scanning electron microscopy, and cyclic voltammetry, alongside experimental validation using chicken heart tissue to simulate healthy and rejected states. The study highlights the potential of EIS in reducing the need for invasive biopsy procedures and offering a promising avenue for early detection and monitoring of organ rejection, with implications for patient care and healthcare resource utilization.
Cancer recurrence can arise owing to rare circulating cancer stem cells (CSCs) that are resistant to chemotherapies and radiotherapies. Here, we show that a double-network hydrogel can rapidly ...reprogramme differentiated cancer cells into CSCs. Spheroids expressing elevated levels of the stemness genes Sox2, Oct3/4 and Nanog formed within 24 h of seeding the gel with cells from any of six human cancer cell lines or with brain cancer cells resected from patients with glioblastoma. Human brain cancer cells cultured on the double-network hydrogel and intracranially injected in immunodeficient mice led to higher tumorigenicity than brain cancer cells cultured on single-network gels. We also show that the double-network gel induced the phosphorylation of tyrosine kinases, that gel-induced CSCs from primary brain cancer cells were eradicated by an inhibitor of the platelet-derived growth factor receptor, and that calcium channel receptors and the protein osteopontin were essential for the regulation of gel-mediated induction of stemness in brain cancer cells.
Due to advances in additive manufacturing and prototyping, affordable and rapid microfluidic sensor-integrated assays can be fabricated using additive manufacturing, xurography and electrode shadow ...masking to create versatile platform technologies aimed toward qualitative assessment of acute cytotoxic or cytolytic events using stand-alone biochip platforms in the context of environmental risk assessment. In the current study, we established a nasal mucosa biosensing platform using RPMI2650 mucosa cells inside a membrane-integrated impedance-sensing biochip using exclusively rapid prototyping technologies. In a final proof-of-concept, we applied this biosensing platform to create human cell models of nasal mucosa for monitoring the acute cytotoxic effect of zinc oxide reference nanoparticles. Our data generated with the biochip platform successfully monitored the acute toxicity and cytolytic activity of 6 mM zinc oxide nanoparticles, which was non-invasively monitored as a negative impedance slope on nasal epithelial models, demonstrating the feasibility of rapid prototyping technologies such as additive manufacturing and xurography for cell-based platform development.
Understanding the physicochemical properties of hydrogel surfaces and their molecular origins is important for their applications. In this paper, we elucidate the molecular origin of surface charges ...in double-network hydrogels synthesized by two-step sequential polymerization. Synthesis of hydrogels by free-radical polymerization does not fully complete the reaction, leaving a small number of unreacted monomers. When this approach is used to synthesize double network (DN) hydrogels by a two-step sequential polymerization from charged monomers for the first network and neutral monomers for the second network, the unreacted first network monomers are incorporated into the second network. Since the surface of such DN hydrogels is covered with a μm-thick layer of the neutral second network, the incorporation of a small amount of charged monomers into the second network increases the surface charge and, thereby, their repulsive/adhesive properties. Therefore, we propose a method to remove unreacted monomers and modulate the surface charge density of DN hydrogels.
Chitin is a biopolymer, which has been proven to be a biomedical material candidate, yet the weak mechanical properties seriously limit their potentials. In this work, a chitin-based double-network ...(DN) hydrogel has been designed as a potential superficial repairing material. The hydrogel was synthesized through a double-network (DN) strategy composing hybrid regenerated chitin nanofiber (RCN)-poly (ethylene glycol diglycidyl ether) (PEGDE) as the first network and polyacrylamide (PAAm) as the second network. The hybrid RCN-PEGDE/PAAm DN hydrogel was strong and tough, possessing Young’s modulus (elasticity) E 0.097 ± 0.020 MPa, fracture stress σf 0.449 ± 0.025 MPa, and work of fracture W f 5.75 ± 0.35 MJ·m–3. The obtained DN hydrogel was strong enough for surgical requirements in the usage of soft tissue scaffolds. In addition, chitin endowed the DN hydrogel with good bacterial resistance and accelerated fibroblast proliferation, which increased the NIH3T3 cell number by nearly five times within 3 days. Subcutaneous implantation studies showed that the DN hydrogel did not induce inflammation after 4 weeks, suggesting a good biosafety in vivo. These results indicated that the hybrid RCN-PEGDE/PAAm DN hydrogel had great prospect as a rapid soft-tissue-repairing material.
Advances in the accessibility of manufacturing technologies and iPSC-based modeling have accelerated the overall progress of organs-on-a-chip. Notably, the progress in multi-organ systems is not ...progressing with equal speed, indicating that there are still major technological barriers to overcome that may include biological relevance, technological usability as well as overall accessibility.INTRODUCTIONAdvances in the accessibility of manufacturing technologies and iPSC-based modeling have accelerated the overall progress of organs-on-a-chip. Notably, the progress in multi-organ systems is not progressing with equal speed, indicating that there are still major technological barriers to overcome that may include biological relevance, technological usability as well as overall accessibility.We here review the progress in the field of multi-tissue- and body-on-a-chip pre and post- SARS-CoV-2 pandemic and review five selected studies with increasingly complex multi-organ chips aiming at pharmacological studies.AREAS COVEREDWe here review the progress in the field of multi-tissue- and body-on-a-chip pre and post- SARS-CoV-2 pandemic and review five selected studies with increasingly complex multi-organ chips aiming at pharmacological studies.We discuss future and necessary advances in the field of multi-organ chips including how to overcome challenges regarding cell diversity, improved culture conditions, model translatability as well as sensor integrations to enable microsystems to cover organ-organ interactions in not only toxicokinetic but more importantly pharmacodynamic and -kinetic studies.EXPERT OPINIONWe discuss future and necessary advances in the field of multi-organ chips including how to overcome challenges regarding cell diversity, improved culture conditions, model translatability as well as sensor integrations to enable microsystems to cover organ-organ interactions in not only toxicokinetic but more importantly pharmacodynamic and -kinetic studies.
The hydrogel chemical structure at the gel-solution interface is important toward practical use, especially in tough double network (DN) hydrogels that have promising applications as structural ...biomaterials. In this work, we regulate the surface chemical structure of DN hydrogels and the surface–bulk transition by the molding substrate used for the synthesis of the second network. To characterize the surface and bulk structure, we combined attenuated total reflectance Fourier-transform infrared spectroscopy and a newly developed microelectrode technique that probe the electric potential distribution within a hydrogel. We found that the polymerization on a repulsive substrate leads to the formation of a thin layer of a second network on the surface of DN hydrogels, which makes the surface different from the bulk. By controlling the second network polymerization conditions and molding substrate, the surface–bulk transition region can be regulated, so that either only the second network or both networks are present at the DN hydrogel surface. Through these findings, we gained a new insight into the structure formation at the DN hydrogel surface, and this leads to easy regulation of the hydrogel surface structure and properties.
Organophosphates (OPs) and carbamates as insecticides, nematicides, fungicides, and herbicides are constantly increasing. Their neurotoxic nature requires careful usage, and misuse can lead to ...fatalities. OPs classified as 'Class 1′ toxic compounds irreversibly inhibit cholinesterases due to their molecular structure resembling the natural acetylcholine substrate, leading to toxic events in the human brain. Monitoring such chemicals is relevant for agricultural applications and essential for the military sector to ensure the safety of personnel and civilian populations. State-of-the-art analytical detection methods require time-consuming pre-treatments and costly reagents and face challenges associated with pesticide properties like thermal lability, low volatility, and high polarity, which can compromise analysis performance. Advanced systems like electrophoresis or liquid chromatography are used to address these, but these are not well suited for field analysis. Miniaturized colorimetric assays are becoming more popular for various portable devices and kits (i.e., metabolic or blood cell assays) due to their ease of use and practicality. Here, we aimed to establish and optimize a straight-forward paper-based microfluidic acetylcholine esterase inhibition assay for mobile organophosphate detection, laying the groundwork for future microdevice modules to be used in environmental monitoring, public health, and CBRN applications.
•Characterization of a microfluidic paper-based acetylcholine inhibition assay parameters for quantitative malathion detection.•Transfer of the optimized protocol to a single-step multiplexed microfluidic device with prestored enzyme and chromogen reservoirs.•Proof-of-concept microdevice study on the inhibitory potential of the organophosphate malathion.
Tough and self‐recoverable hydrogel membranes with micrometer‐scale thickness are promising for biomedical applications, which, however, rarely be realized due to the intrinsic brittleness of ...hydrogels. In this work, for the first time, by combing noncovalent DN strategy and spin‐coating method, we successfully fabricated thin (thickness: 5–100 µm), yet tough (work of extension at fracture: 105–107 J m−3) and 100% self‐recoverable hydrogel membranes with high water content (62–97 wt%) in large size (≈100 cm2). Amphiphilic triblock copolymers, which form physical gels by self‐assembly, were used for the first network. Linear polymers that physically associate with the hydrophilic midblocks of the first network, were chosen for the second network. The inter‐network associations serve as reversible sacrificial bonds that impart toughness and self‐recovery properties on the hydrogel membranes. The excellent mechanical properties of these obtained tough and thin gel membranes are comparable, or even superior to many biological membranes. The in vitro and in vivo tests show that these hydrogel membranes are biocompatible, and postoperative nonadhesive to neighboring organs. The excellent mechanical and biocompatible properties make these thin hydrogel membranes potentially suitable for use as biological or postoperative antiadhesive membranes.
Thin (5–100 µm), tough, and fully self‐recoverable hydrogel membranes (≈75 wt% water content) are successfully fabricated based on the double‐network concept. The membranes exhibit excellent mechanical properties superior to those of various biological membranes, biocompatibility, and postoperative antiadhesive property, foreshadowing their potential use as substitutes for biological membranes or postoperative antiadhesive membranes.
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