Opal Hydrogel Research Articles

Melanin Hydrogel Inverse Opal Microneedle Patches for Wound Healing.

Bacterial infected wounds bring an economic burden to the worldwide medical care field. A variety of bioactives-integrated hydrogel patches are developed in response to this challenge. Here, the melanin hydrogel inverse opal microneedle patches (MNs) with antioxidant and visual color sensing abilities for the management of bacterial infected wounds are proposed. The MNs are fabricated by applying melanin-loaded polyethylene glycol diacrylate (PEGDA) as the inverse opal hydrogel and using bacitracin-carried gelatin to fill those nanopores of hydrogel scaffold. Benefitting from the antioxidant capacity of melanin nanoparticles and the local antimicrobial ability of bacitracin, the resulting MNs possess the integrated functions of reactive oxygen species scavenging and antibacterial. Besides, the inverse opal structure endows the MNs with vivid structure color and detectable reflected wavelength, which can gradually shift with the release of the drug, thus allowing MNs to assess the drug delivery. Based on these characteristics, MNs perform excellent in in vitro drug delivery and monitoring, as well as the promotion of bacterial infected wound recovery in vivo, indicating the potential of MNs in the future wound management field.

Long‐Term Monitoring of ApoE4 within Aqueous Humor Using Intraocular Lenses Containing Target‐Responsive Inverse Opal Hydrogel

Neurodegenerative diseases, including Alzheimer's disease (AD), pose significant challenges to global healthcare because of their irreversible postsymptomatic progression. Conventional radiographic techniques have limitations in early detection, owing to the time lapse between symptom recognition by individuals and precise inspection using medical instruments. Current research explores ophthalmic approaches to address this gap, investigating the physiological link between ocular health and brain diseases. Intraocular lenses (IOLs), widely used in cataract and refractive surgeries, provide a safe and minimally invasive platform for the continuous monitoring of neurodegenerative disease biomarkers, including those associated with AD. By integrating biomolecule‐responsive sensors with IOLs, it becomes feasible to achieve early diagnosis and long‐term, noninvasive monitoring postimplantation. Herein, a fluorescently labeled inverse opal hydrogel (FIOH) is merged with IOLs for ApoE4 detection, a key risk factor for AD. The permeability and inherent photonic properties of FIOH facilitate the cumulative enhancement of the fluorescence signal. In a simulation of the aqueous humor circulation, the detection limit for ApoE4 is determined to be 0.1 nM. Therefore, FIOH‐integrated IOLs hold promise not only for early detection but also for providing a reliable platform for the continuous, noninvasive monitoring of neurodegenerative diseases after the initial, minimally invasive implantation.

Tailoring esophageal tumor spheroids on a chip with inverse opal scaffolds for drug screening

Esophageal cancer (EC) is characterized by high morbidity and mortality, and chemotherapy has become an indispensable means for comprehensive treatment. However, due to the limitation of the effective in vitro disease model, the development of chemotherapeutic agents still faces great challenges. In this paper, we present a novel tumor spheroid on a chip platform based on inverse opal hydrogel scaffolds to screen chemotherapeutic agents for EC treatment. With the microfluidic emulsion approach, the inverse opal hydrogel scaffolds were generated with tunable and organized pores, which could provide spatial confinement for cell growth. Thus, the suspended KYSE-70 cells could successfully form uniform cell spheroids on the inverse opal hydrogel scaffolds. It was demonstrated that the tumor cell spheroids could recapitulate 3D growth patterns in vivo and exhibited higher sensitivity to the chemotherapy agents compared with monolayer cells. Besides, by employing the scaffolds into a microfluidics to construct esophageal tumor on a chip, the device could realize high-throughput tumor cell spheroids generation and drug screening, indicating its promising role in chemotherapy drug development.

Rapid Fabrication of Large-Grain Opal Films and Photonic Crystal Hydrogel Sensors by a Filter Paper-Enhanced Evaporation Chip.

Developing a rapid fabrication method for crack-free opal films is a significant challenge with broad applications. We developed a microfluidic platform known as the "filter paper-enhanced evaporation microfluidic chip" (FPEE-chip) for the fabrication of photonic crystal and inverse opal hydrogel (IOPH) films. The chip featured a thin channel formed by bonding double-sided adhesive poly(ethylene terephthalate) with a polymethyl methacrylate cover and a glass substrate. This channel was then filled with nanosphere colloids. The water was guided to evaporate rapidly at the surface of the filter paper, allowing the nanospheres to self-assemble and accumulate within the channel under capillary forces. Experimental results confirmed that the self-assembly method based on the FPEE-chip was a rapid platform for producing high-quality opal, with centimeter-sized opal films achievable in less than an hour. Furthermore, the filter paper altered the stress release mechanism of the opal films during drying, resulting in fewer cracks. This platform was proven capable of producing large-grain, crack-free opal films of up to 30 mm2 in size. We also fabricated crack-free IOPH pH sensors that exhibited color and size responsiveness to pH changes. The coefficient of variation of the gray color distribution for crack-free IOPH ranged from 0.03 to 0.07, which was lower than that of cracked IOPH (ranging from 0.07 to 0.14). Additionally, the grayscale peak value in 1 mm2 of the crack-free IOPH was more than twice that of the cracked IOPH at the same pH. The FPEE-chip demonstrated potential as a candidate for developing vision sensors.

Biomimetic Anticoagulated Porous Particles with Self-Reporting Structural Colors.

Anticoagulation is vital to maintain blood fluidic status and physiological functions in the field of clinical blood-related procedures. Here, novel biomimetic anticoagulated porous inverse opal hydrogel particles is presented as anticoagulant bearing dynamic screening capability. The inverse opal hydrogel particles possess abundant sulfonic and carboxyl groups, which serve as binding sites with multiple coagulation factors and inhibit the blood coagulation process. Owing to the variations of refractive index and pore sizes during the binding process, the particles appeared corresponding structure color variations, which can be adopted as sensory index of anticoagulation. Based on these features, a sensor containing these diverse structure color particle units is constructed for pattern recognition of coagulation factors level in clinical plasma samples. By analyzing the sensory information of the unit, the colorimetric "fingerprint" for each target can be obtained and summarized as a database. Besides, a portable test-strip integrating sensory units is developed to distinguish the sample regarding abnormal coagulation factors-derived diseases via multivariate data analysis. It is believed that such biomimetic anticoagulated structural color particles and their derived sensor will open new avenue for clinical detection and disease diagnosis.

Opal photonic crystal double‐network hydrogel for visual detection through structural color and fluorescent responsiveness

AbstractPhotonic crystal hydrogels are widely used in the field of visual detection, based on the response of the structural color to external stimulus, such as pH, temperature, near‐infrared light, and so on. Here, we develop an opal photonic crystal hydrogel by combining polystyrene (PS) photonic crystals with a fluorescent double‐network hydrogel and focus on both its visual detection function and mechanical property. The opal hydrogel is composed of nanocomposite hydrogel as the first network and ionic crosslinked hydrogel as the second network. The introduction of PS photonic crystals and terbium ions endows the opal hydrogel distinctive structural colors and fluorescence, respectively. Because of volume changes, the structural color of the opal hydrogel selectively responses to metal ions and organic solvents. Attributing to the ion exchange interaction, the opal hydrogel exhibits fluorescent responses to various metal ions. Combining the responsiveness of structural color and fluorescence, a visual dual‐detection mode is set up, with better detection sensitivity and selectivity. Moreover, the characteristics of nanocomposite and double‐network crosslinking ensure the opal hydrogel enough mechanical properties to undergo cycle visual detection. Consequently, the fabricated opal hydrogel is promising for use in visual detection to multiple substances in single‐ or dual‐detection mode.

Multicargo-loaded inverse opal gelatin hydrogel microparticles for promoting bacteria-infected wound healing

Nowadays, many strategies have been developed to design biomaterials to accelerate bacteria-infected wound healing. Here, we presented a new type of multicargo-loaded inverse opal hydrogel microparticle (IOHM) for regulating oxidative stress, antibiosis, and angiogenesis of the bacteria-infected wound. The methacrylate acylated gelatin (GelMA)-based inverse opal hydrogel microparticles (IOHMs) were obtained by using the colloidal crystal microparticles as templates, and fullerol, silver nanoparticles (Ag NPs), and vascular endothelial growth factor (VEGF) were loaded in IOHMs. The developed multicargo-loaded IOHMs displayed good size distribution and biocompatibility, and when they were applied in cell culture, bacteria culture, and animal experiments, they exhibited excellent anti-oxidative stress properties, antibacterial properties, and angiogenesis. These characteristics of the developed multicargo-loaded IOHMs make them ideal for bacteria-infected wound healing.

Black phosphorus hydrogel inverse opal microneedle patches for psoriasis treatment

Microneedle patches (MNs) have demonstrated potentials in transdermal drug delivery for skin disease therapy. Effort is mainly focused on the improvement of MNs’ materials, structures and functions to realize intelligent drug delivery. Here, we propose a novel black phosphorus (BP)-loaded hydrogel inverse opal MNs with photothermal responsive capacity and vivid structural color screening for psoriasis treatment. The MNs, composed of a BP-loaded N-isopropyl acrylamide (NIPAM)/poly(ethylene glycol) diacrylate (PEGDA) inverse opal hydrogel scaffold and the drug-carrying gelatin/agarose filler inside the scaffold pores, are fabricated through combined approaches of nanoparticle assembly, reversed-phase replication and micro-molding. Due to the photothermal conversion of BP, temperature-responsive shrinkage of NIPAM, and heat-sensitive gelatin, the resulting MNs obtain the ability of good hydrophobic drug loading and photothermal controllable drug release. In addition, profiting from the inverse opal structure with optical properties, the MNs exhibit a bright structural color and can generate characteristic wavelength shift during drug release, providing a real-time monitoring and feedback for drug delivery. Based on these features, the MNs show excellent in vivo drug administration and efficient psoriasis treatment in mice, indicating their potential as intelligent drug delivery vehicles for practical applications.

Immobilization of laccase on magnetic PEGDA–CS inverse opal hydrogel for enhancement of bisphenol A degradation in aqueous solution

Endocrine disruptors such as bisphenol A (BPA) adversely affect the environment and human health. Laccases are used for the efficient biodegradation of various persistent organic pollutants in an environmentally safe manner. However, the direct application of free laccases is generally hindered by short enzyme lifetimes, non-reusability, and the high cost of a single use. In this study, laccases were immobilized on a novel magnetic three-dimensional poly(ethylene glycol) diacrylate (PEGDA)–chitosan (CS) inverse opal hydrogel (LAC@MPEGDA@CS@IOH). The immobilized laccase showed significant improvement in the BPA degradation performance and superior storage stability compared with the free laccase. 91.1% of 100 mg/L BPA was removed by the LAC@MPEGDA@CS@IOH in 3 hr, whereas only 50.6% of BPA was removed by the same amount of the free laccase. Compared with the laccase, the outstanding BPA degradation efficiency of the LAC@MPEGDA@CS@IOH was maintained over a wider range of pH values and temperatures. Moreover, its relative activity of was maintained at 70.4% after 10 cycles, and the system performed well in actual water matrices. This efficient method for preparing immobilized laccases is simple and green, and it can be used to further develop ecofriendly biocatalysts to remove organic pollutants from wastewater.

Artificial cells from microfluidic electrospray for reactive oxygen species scavenging

Excess reactive oxygen species (ROS) are closely related to many diseases, and the removal of ROS is a crucial strategy for facilitating clinical treatment. Herein, inspired by the multicompartment and the ROS-eliminating pathway within cells, an artificial cell containing enzymatic inverse opal hydrogel particles (IOHPs) for ROS scavenging is presented. The IOHPs with different colors are integrated into the prepared artificial cells through a microfluidic electrospray platform. Benefiting from the structural color marks of the IOHPs and the fluid manipulability of the microfluidic electrospray technique, the composited artificial cells with tunable numbers and types of encapsulated enzymes were developed. The resultant artificial cells displayed excellent capability in scavenging ROS, and when they were used for the treatment of culture medium, they could protect the cells from ROS-related damage. These features indicate that such biomimetic microcapsules with artificial cell structures can be a powerful therapeutic tool for the treatment of ROS-related diseases.

A smartphone-based inverse opal hydrogel film aptasensor for mycotoxin detection by the naked eye

Ochratoxin A (OTA), a carcinogenic mycotoxins, poses a significant threat to human health. The current detection methods exhibit advantages such as high sensitivity and good selectivity. However, The methods applicability for on-site detection remains hindered by complex operational procedures and the requirement for bulky testing instruments. Here, to address this limitation, we present a novel portable platform for naked-eye detection of OTA using photonic crystal (PC) inverse opal hydrogel films based on the smartphone. The inverse opal hydrogel film was fabricated by integrating hydrogel within PC templates, while a binding aptamer was employed to selectively recognize OTA. In the absence of OTA, the film displayed a vibrant red. With increasing OTA concentration, the diffraction peak progressively shifted toward the blue region of the spectrum. Leveraging a portable microscope, and captured the color change using a smartphone and developed a self-written algorithm to extract the H value of the image, enabling quantitative detection of OTA concentration. This portable platform has demonstrated exceptional reliability and convenience, boasting a remarkable detection limit of 1 μg/mL. Furthermore, its versatility extends to the detection of other mycotoxins, making it a promising tool for broader mycotoxin detection applications.

Robust and Reliable Fabrication of Gelatin Films Containing Micropatterned Opal Structures via Evaporative Deposition and Thermal Gelation.

Biopolymeric hydrogel materials containing tunable optical properties such as micropatterned artificial opal structures hold significant potential in various applications. Despite recent advances in fabrication techniques, simple, reliable, and tunable production of stimuli-responsive micropatterned opal hydrogels under mild conditions remains challenging. We report a simple micromolding-based evaporative deposition-thermal gelation technique for gelatin films that capture uniform opal micropatterns, aided by a potent aminopolysaccharide chitosan (CS) that provides binding affinity and structural stability. Our results show reliable, tunable, and high-fidelity fabrication of gelatin hydrogel films containing CS-opal micropatterns, while the as-prepared films show responsiveness to pH, ionic strength, and water content indicating a robust nature. Uniform CS-opal microparticles can also be readily prepared via removal of the gelatin through various simple routes, illustrating the crucial roles of CS and gelatin. We envision that this robust, reliable, and simple evaporative deposition-thermal gelation technique can be readily extended to prepare responsive biopolymeric materials for various applications.

Aptamer-Functionalized Barcodes in Herringbone Microfluidics for Multiple Detection of Exosomes.

Tumor-derived exosomes are vital for clinical dynamic and accurate tumor diagnosis, thus developing sensitive and multiple exosomes detection technology has attracted remarkable attention of scientists. Here, a novel herringbone microfluidic device with aptamer-functionalized barcodes integration for specific capture and multiple detection of tumor-derived exosomes is presented. The barcodes with core-shell constructions are obtained by partially replicating the periodically ordered hexagonal close-packaged colloidal crystal beads. As their inverse opal hydrogel shell possesses rich interconnected pores, the barcodes could provide abundant surface area for functionalization of DNA aptamers to realize specific recognition of target exosomes. Besides, the encoded structure colors of the barcodes can be maintained stably during the detection events as their hardish cores are with sufficient mechanical strength. It is demonstrated that by embedding these barcodes in herringbone groove microfluidic device with designed patterns, the specific capture efficiency and synergetic detection of multiple tumor-derived exosomes in peripheral blood can be significantly improved due to enhanced resistance of turbulent flow. These features make the aptamer-functionalized barcodes and herringbone microfluidics integrated platform promising for exosomes extraction and dynamic tumor diagnosis.

Enhanced human T cell expansion with inverse opal hydrogels.

Advanced personalized immunotherapies still have to overcome several biomedical and technical limitations before they become a routine cancer treatment in spite of recent achievements. In adoptive cell therapy (ACT), the capacity to obtain adequate numbers of therapeutic T cells in the patients following ex vivo treatment should be improved. Moreover, the time and costs to produce these T cells should be reduced. In this work, inverse opal (IOPAL) 3D hydrogels consisting of poly(ethylene) glycol (PEG) covalently combined with heparin were engineered to resemble the environment of lymph nodes, where T cells get activated and proliferate. The introduction of an IOPAL strategy allowed a precise control on the porosity of the hydrogels, providing an increase in the proliferation of primary human CD4+ T cells, when compared with state-of-the-art expansion systems. Additionally, the IOPAL hydrogels also showed a superior expansion compared to hydrogels with the same composition, but without the predetermined pore structure. In summary, we have shown the beneficial effect of having an IOPAL architecture in our 3D hydrogels to help achieving large numbers of cells, while maintaining the desired selected phenotypes required for ACT.

Enzyme-functionalized structural color hydrogel particles for urea detection and elimination

Excessive urea causes poor stress resistance in plants as well as severe environmental issues. In this work, novel structural color hydrogel particles that can degrade and detect urea simultaneously were developed. Inverse opal hydrogel particles (IOHPs) with abundant carboxyl groups and immobilized urease were used. The particles could hydrolyze urea in a solution to determine the concentration of urea. Moreover, because the detection and elimination relied on specific enzyme catalysis and the pH responsiveness of the sensors, the particles displayed high specificity and sensitivity. When the proper ratio of crosslinker and monomer was chosen, the IOHP sensors responded to the urea solution with a concentration range of 0–30 mM and exhibited a linear range of 1–5 mM with a detection limit of 0.48 mM, which matched the actual demands. The IOHP sensors were applied to practical samples, and it was demonstrated that the recoveries reached ideal percentages of 94.7%–102%. All the results indicate that IOHP sensors are promising for opening a new route for the detection and elimination of urea.

Reversed-engineered human alveolar lung-on-a-chip model

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.

NIR responsive AuNR/pNIPAM/PEGDA inverse opal hydrogel microcarriers for controllable drug delivery

A novel inverse opal microcarrier with both NIR-controlled release and visual color changes for drug delivery.

Fast inverse opal humidity sensor based on acrylamide/AMPS hydrogel

A new fast humidity sensitive inverse opal hydrogel was fabricated through the copolymerization of acrylamide, 2-acrylamido-2-methylpropane sulfonic acid (AMPS), and N,Nʹ-Methylene-bis-acrylamide within the interstitial space of a highly monodisperse polystyrene opal template, followed by template etching. Ultraviolet-visible is the spectroscopy results of the sensor in different relative humidity (RH) levels demonstrated various optical reflection peaks within the visible wavelength range so that the Bragg diffraction peak of inverse opal hydrogel (IOH) red-shifted 88 nm from 426 nm (violet) to 514 nm (green) by increasing RH from 20 to 90 %. Using the optimum amount of AMPS as a functional comonomer in the hydrogel structure, the sensitivity of the IOH humidity sensor (Δλ) increased considerably about 90 nm instead of previous IOH humidity sensors reported by Barry et al. In addition, the comparison between IOH humidity sensors with and without AMPS represented that the first group has more speed in responding to stimuli. Further, the sensor had highly good adhesion to the glass substrate and could be used as a pH paper. Furthermore, it changed its optical reflection peak by increasing environmental RH within a few seconds (less than 2 s) and quickly returned to its original state as humidity indicated a decrease. Finally, RH increase/decrease cycles revealed that the sensor has a long lifetime (more than one year) without response time degradation or reproducibility.

Colorimetric monitoring of humidity by opal photonic hydrogel

The present study demonstrated a new fast colorimetric humidity sensor using the opal hydrogel composite (OHC). First, a highly monodisperse polystyrene (PS) latex was synthesized by soap-free emulsion polymerization and deposited on a glass substrate in order to form a three-dimensional opal photonic crystal. Then, the homogenous hydrogel precursor was infiltrated into the interstitial space of opal by capillary forces and underwent chemical polymerization to construct an embedded PS crystalline colloidal array within a poly (acrylamide-co-acrylic acid) hydrogel network. The scanning electron microscopic images confirmed the formation of opal structures. An interesting feature of the presented OHC sensor is that the sensor is transparent in a dry state and an increase in relative humidity (RH) leads to a colorful film. In addition, UV/Vis spectroscopy was performed within an RH range of 25–95%, indicating that reflection peak height gradually develops by RH increasing and the peak position shifts from 413 to 518 nm. Further, the sensor functions extremely rapidly and changes its color by increasing RH within a few seconds (less than 3 s) and becomes transparent again quickly as humidity represents a decrease. Based on the results, repeated humidity changes revealed that the sensor has an excellent reproducibility without any reduction in response time and sensitivity or a color change. Finally, it has good adhesion to the glass substrate which makes it a suitable RH sensor in different applications, along with the rapid response time, high sensitivity, repeatability, and the visual alarm.

Numerical simulation of pillars and electromagnetic mode coupling for nanoparticle sensors

Sensors based on the response of the photonic crystal in imprint polymers (hydrogels) have recently attracted considerable attention for visual medical diagnostics, pharmaceutical bioassays, environmental monitoring, and nanoparticle detection. These applications often use the variation of the wavelength as a function of the diameter of the air sphere (inverse opal hydrogels) according to the Bragg equation at a fixed incident angle. However, these promising materials mixed with fluorescent nanocrystals for the detection of targeted nanoparticles have never been explored so far with the finite differential time-domain (FDTD) method, electric field intensity map, and radiated power profile at far-field. In this paper, we have combined silicon nanopillars, nanoparticles, imprint polymers, and nanocrystal fluorescence. The sensitivity of the sensor we simulate depends on the nanocrystal fluorescence variation when the imprint polymer swells (polymer thickness variation). We have shown numerically that the electric field intensity at far-field is at a maximum in the pillar’s symmetrical axis when the dipole (representing the nanocrystal) polarization is perpendicular to the pillar. Also, we have shown that radiated power is increasing and monotone when the thickness of the imprint polymer evolves between 498 and 912 nm. The purpose of this numerical simulation is to develop a nanoparticle sensor with high sensitivity, high selectivity, and an efficient detection device.