Hydrogel-based Platform Research Articles

Label-Free Monitoring of Coculture System Dynamics: Probing Probiotic and Cancer Cell Interactions via Infrared Spectroscopic Imaging.

Evaluating the dynamic interaction of microorganisms and mammalian cells is challenging due to the lack of suitable platforms for examining interspecies interactions in biologically relevant coculture conditions. In this work, we demonstrate the interaction between probiotic bacteria (Lactococcus lactis and Escherichia coli) and A498 human cancer cells in vitro, utilizing a hydrogel-based platform in a label-free manner by infrared spectroscopy. The L. lactis strain recapitulated in the compartment system secretes polypeptide molecules such as nisin, which has been reported to trigger cell apoptosis. We propose a mid-infrared (IR) spectroscopic imaging approach to monitor the variation of biological components utilizing kidney cells (A498) as a model system cocultured with bacteria. We characterized the biochemical composition (i.e., nucleic acids, protein secondary structures, and lipid conformations) label-free using an unbiased measurement. Several IR spectral features, including unsaturated fatty acids, β-turns in protein, and nucleic acids, were utilized to predict cellular response. These features were then applied to establish a quantitative relationship through a multivariate regression model to predict cellular dynamics in the coculture system to assess the effect of nisin on A498 kidney cancer cells cocultured with bacteria. Overall, our study sheds light on the potential of using IR spectroscopic imaging as a label-free tool to monitor complex microbe-host cell interactions in biological systems. This integration will enable mechanistic studies of interspecies interactions with insights into their underlying physiological processes.

Recent advances and trends in innovative biosensor-based devices for heavy metal ion detection in food.

Low-cost, reliable, and efficient biosensors are crucial in detecting residual heavy metal ions (HMIs) in food products. At present, based on distance-induced localized surface plasmon resonance of noble metal nanoparticles, enzyme-mimetic reaction of nanozymes, and chelation reaction of metal chelators, the constructed optical sensors have attracted wide attention in HMIs detection. Besides, based on the enrichment and signal amplification strategy of nanomaterials on HMIs and the construction of electrochemical aptamer sensing platforms, the developed electrochemical biosensors have overcome the plague of low sensitivity, poor selectivity, and the inability of multiplexed detection in the optical strategy. Moreover, along with an in-depth discussion of these different types of biosensors, a detailed overview of the design and application of innovative devices based on these sensing principles was provided, including microfluidic systems, hydrogel-based platforms, and test strip technologies. Finally, the challenges that hinder commercial application have also been mentioned. Overall, this review aims to establish a theoretical foundation for developing accurate and reliable sensing technologies and devices for HMIs, thereby promoting the widespread application of biosensors in the detection of HMIs in food.

A Comprehensive Review of Hydrogel-Based Drug Delivery Systems: Classification, Properties, Recent Trends, and Applications.

As adaptable biomaterials, hydrogels have shown great promise in several industries, which include the delivery of drugs, engineering of tissues, biosensing, and regenerative medicine. These hydrophilic polymer three-dimensional networks have special qualities like increased content of water, soft, flexible nature, as well as biocompatibility, which makes it excellent candidates for simulating the extracellular matrix and promoting cell development and tissue regeneration. With an emphasis on their design concepts, synthesis processes, and characterization procedures, this review paper offers a thorough overview of hydrogels. It covers the various hydrogel material types, such as natural polymers, synthetic polymers, and hybrid hydrogels, as well as their unique characteristics and uses. The improvements in hydrogel-based platforms for controlled drug delivery are examined. It also looks at recent advances in bioprinting methods that use hydrogels to create intricate tissue constructions with exquisite spatial control. The performance of hydrogels is explored through several variables, including mechanical properties, degradation behaviour, and biological interactions, with a focus on the significance of customizing hydrogel qualities for particular applications. This review paper also offers insights into future directions in hydrogel research, including those that promise to advance the discipline, such as stimuli-responsive hydrogels, self-healing hydrogels, and bioactive hydrogels. Generally, the objective of this review paper is to provide readers with a detailed grasp of hydrogels and all of their potential uses, making it an invaluable tool for scientists and researchers studying biomaterials and tissue engineering.

Selectively cross-linked hydrogel-based cocktail drug delivery micro-chip for colon cancer combinatorial drug screening using AI-CSR platform for precision medicine.

Cancer, ranked as the second leading cause of global mortality with a prevalence of 1 in 6 deaths, necessitates innovative approaches for effective treatment. Combinatorial drug therapy for cancer treatment targets several key pathways simultaneously and potentially enhances anti-cancer efficacy without intolerable side effects. However, it demands precise and accurate control of drug-dose combinations and their release. In this study, we demonstrated a selectively cross-linked hydrogel-based platform that can quantify and release drugs simultaneously for in-parallel cocktail drug screening. PDMS was used as the flow channel substrate and the poly (ethylene glycol) diacrylate (PEGDA) hydrogel array was formed by UV exposure using the photomask. Employing our platform, cocktails of anticancer drugs are precisely loaded and simultaneously released in-parallel into HCT-116 colon cancer cells, facilitating combinatorial drug screening. The integration of an artificial intelligence-based complex system response (AI-CSR) platform successfully identifies optimal drug-dose combinations from a pool of ten approved drugs. Notably, our cocktail drug chip demonstrates exceptional efficiency, screening 155 drug-dose combinations within a brief two and a half hours, a marked improvement over traditional methods. Furthermore, the device exhibits low drug consumption, requiring a mere 1 μL per patch of chip. Thus, our developed PDMS drug-loaded hydrogel platform presents a novel and expedited approach to quantifying drug concentrations, promising to be a faster, efficient and more precise approach for conducting cocktail drug screening experiments.

A Shape Memory Hydrogel with Excellent Mechanical Properties, Water Retention Capacity, and Tunable Fluorescence for Dual Encryption.

Information encryption platforms with reliable encryption performance, excellent mechanical performance, and high water retention capacity are highly desired. In this study, a tough double-network hydrogel is designed using the first network of a polyion complex containing lanthanide complexes via one-pot polymerization and the second network of a poly (N-hydroxyethyl acrylamide) (PHEAA) obtained by deep eutectic solvent (DES)-assisted introduction and subsequent photopolymerization. In this system, the pH-induced shape memory function and pH-/wavelength-dependent fluorescence allow the use of the prepared hydrogel as a dual-encryption platform. Owing to its high response reversibility, the hydrogel-based platform exhibits both a high security level and the advantages of rewritability, reprogrammability, and reusability. Additionally, the excellent mechanical properties and water retention capacity owing to the solvent exchange process involving the low-volatility solvent DES and the resulting introduction of the second network of PHEAA offer high practical application value for the hydrogel-based dual encryption platform, demonstrating its potential for information security protection.

Transfer-Printing Hydrogel-Based Platform for Moisture-Driven Dynamic Display and Optical Anti-Counterfeiting.

Humidity-responsive materials offer a promising approach to achieving tunable metasurface systems due to their fast and reversible swelling responses to moisture, which enables many important applications, such as real-time humidity sensing, optical switches, dynamic displays, and optical information encryption. However, the humidity-responsive structural coloration generally cannot provide a high spatial resolution and requires a complex patterning process. Here, we present a scalable moisture-driven color-changing Fabry-Pérot (FP)-like cavity composed of a polyvinyl alcohol layer sandwiched between an upper gold nanoparticles assembly and a bottom gold mirror. Through nanoparticle contact printing, we pixelated these cavities with sub-micrometer sizes without crosstalk and achieved an ultrahigh display resolution of ∼400 nm. Meanwhile, these nanoparticle-based FP (NBFP) cavities exhibit more vibrant colors than those of conventional film-based ones due to broadband absorption of the disordered nanoparticle assembly. Moreover, the NBFP cavities exhibit a rapid response (<300 ms), benefiting from the membrane pores formed in the gaps between the adjacent nanoparticles. Finally, we demonstrated the applications of the NBFP cavities in optical anti-counterfeiting and dynamic multi-color printing. These results suggest that our approach will help to realize a colorful, fast, and ultrahigh-resolution dynamic display device in optical security and colorimetric sensing.

An In Vitro and Ex Vivo Analysis of the Potential of GelMA Hydrogels as a Therapeutic Platform for Preclinical Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating condition with no curative therapy currently available. Immunomodulation can be applied as a therapeutic strategy to drive alternative immune cell activation and promote a proregenerative injury microenvironment. Locally injected hydrogels carrying immunotherapeutic cargo directly to injured tissue offer an encouraging treatment approach from an immunopharmacological perspective. Gelatin methacrylate (GelMA) hydrogels are promising in this regard, however, detailed analysis on the immunogenicity of GelMA in the specific context of the SCI microenvironment is lacking. Here, the immunogenicity of GelMA hydrogels formulated with a translationally relevant photoinitiator is analyzed in vitro and ex vivo. 3% (w/v) GelMA, synthesized from gelatin type-A, is first identified as the optimal hydrogel formulation based on mechanical properties and cytocompatibility. Additionally, 3% GelMA-A does not alter the expression profile of key polarization markers in BV2 microglia or RAW264.7 macrophages after 48h. Finally, it is shown for the first time that 3% GelMA-A can support the ex vivo culture of primary murine organotypic spinal cord slices for 14 days with no direct effect on glial fibrillary acidic protein (GFAP+ ) astrocyte or ionized calcium-binding adaptor molecule 1 (Iba-1+ ) microglia reactivity. This provides evidence that GelMA hydrogels can act as an immunotherapeutic hydrogel-based platform for preclinical SCI.

Poly(N-vinylcaprolactam)-Gold Nanorods-5 Fluorouracil Hydrogels: In the Quest of a Material for Topical Therapies against Melanoma Skin Cancer.

Chemically crosslinked hydrogels based on poly(N-vinylcaprolactam) (PNVCL) were synthetized by a photoinitiated chemical method. A galactose-based monomer, 2-lactobionamidoethyl methacrylate (LAMA), and N-vinylpyrrolidone (NVP) were added with the aim to improve the physical and chemical properties of hydrogels. The effects of both comonomers on the swelling ratio (Q), volume phase transition temperature (VPTT), glass transition temperature (Tg), and Young's moduli by mechanical compression below and above the VPTT were studied. Gold nanorods (GNRDs) and 5-fluorouracil (5FU) were embedded into the hydrogels, to study the drug release profiles with and without the excitation of GNRDs by irradiation in the near-infrared region (NIR). Results showed that the addition of LAMA and NVP increased the hydrogels' hydrophilicity, elasticity, and VPTT. The loading of GNRDs in the hydrogels changed the release rate of 5FU when irradiated intermittently with an NIR laser. The present study reports on the preparation of a hydrogel-based platform of PNVCL-GNRDs-5FU as a potential hybrid anticancer hydrogel for chemo/photothermal therapy that could be applied against skin cancer for topical 5FU delivery.

Migration and 3D Traction Force Measurements inside Compliant Microchannels.

Cells migrate in vivo through channel-like tracks. While polydimethylsiloxane devices emulate such tracks in vitro, their channel walls are impermeable and have supraphysiological stiffness. Existing hydrogel-based platforms address these issues but cannot provide high-throughput analysis of cell motility in independently controllable stiffness and confinement. We herein develop polyacrylamide (PA)-based microchannels of physiological stiffness and prescribed dimensions for high-throughput analysis of cell migration and identify a biphasic dependence of speed upon confinement and stiffness. By utilizing novel four-walled microchannels with heterogeneous stiffness, we reveal the distinct contributions of apicolateral versus basal microchannel wall stiffness to confined versus unconfined migration. While the basal wall stiffness dictates unconfined migration, apicolateral stiffness controls confined migration. By tracking nanobeads embedded within channel walls, we innovate three-dimensional traction force measurements around spatially confining cells at subcellular resolution. Our unique and highly customizable device fabrication strategy provides a physiologically relevant in vitro platform to study confined cells.

Ultra stretchable, tough, elastic and transparent hydrogel skins integrated with intelligent sensing functions enabled by machine learning algorithms

Hydrogel-based ionic skins are ionic conductive artificial skin-like materials that are promising for a broad range of applications such as wearable sensory devices, soft robotics and machines, and bioelectronics. However, fabricating hydrogel skins with satisfying mechanical performance and intelligent sensing functions is still a significant challenge. Herein, we have developed an ionic conductive nanocomposite hydrogel with ultra stretchability and self-evolving sensing functions. By leveraging the dynamic feature of synergetic interfacial ionic interactions, a trace amount of carbon nanotubes endows the hydrogel networks with excellent mechanical performances (i.e., tensile strength, stretchability and toughness up to 1.09 MPa, 4075 % and 12.8 MJ/m3, respectively). Additionally, the hydrogel is soft, elastic, transparent and self-healing. The rational combination of the mechanical and electrical properties renders the as-prepared hydrogel with excellent sensing performances and cycling stability, and therefore enables it to perform as a sensory unit of a complete platform for the recognition of some complicated human behaviors, outperforming the previously reported hydrogels due to its intelligent sensing functions. Specifically, with the integration of machine learning module, the hydrogel-based platform exhibits great recognition accuracies to human handwriting motions from single letters to words, phrases, and short sentences after proper training. The combination of superior mechanical performances and self-evolving sensing functions within this hydrogel-based ionic skin unlocks its potential as the intelligent human-device interface, which promotes the application of artificial intelligence in customized electronic devices.

Self-Healing, Stretchable, Biocompatible, and Conductive Alginate Hydrogels through Dynamic Covalent Bonds for Implantable Electronics.

Implantable electronics have recently been attracting attention because of the promising advances in personalized healthcare. They can be used to diagnose and treat chronic diseases by monitoring and applying bioelectrical signals to various organs. However, there are challenges regarding the rigidity and hardness of typical electronic devices that can trigger inflammatory reactions in tissues. In an effort to improve the physicochemical properties of conventional implantable electronics, soft hydrogel-based platforms have emerged as components of implantable electronics. It is important that they meet functional criteria, such as stretchability, biocompatibility, and self-healing. Herein, plant-inspired conductive alginate hydrogels composed of “boronic acid modified alginate” and “oligomerized epigallocatechin gallate,” which are extracted from plant compounds, are proposed. The conductive hydrogels show great stretchability up to 500% and self-healing properties because of the boronic acid-cis-diol dynamic covalent bonds. In addition, as a simple strategy to increase the electrical conductivity of the hydrogels, ionically crosslinked shells with cations (e.g., sodium) were generated on the hydrogel under physiological salt conditions. This decreased the resistance of the conductive hydrogel down to 900 ohm without trading off the original properties of stretchability and self-healing. The hydrogels were used for “electrophysiological bridging” to transfer electromyographic signals in an ex vivo muscle defect model, showing a great bridging effect comparable to that of a muscle-to-muscle contact model. The use of plant-inspired ionically conductive hydrogels is a promising strategy for designing implantable and self-healable bioelectronics.

Novel methods to extract and quantify sensors based on single wall carbon nanotube fluorescence from animal tissue and hydrogel-based platforms

Sensors that can quickly and accurately diagnose and monitor human health are currently at the forefront of medical research. Single walled carbon nanotube (SWNT) based optical biosensors are a growing area of research due to the high spatiotemporal resolution of their near infrared fluorescence leading to high tissue transparency and unparalleled sensitivity to analytes of interest. Unfortunately, due to the functionalization requirements of SWNT-based sensors, there are concerns surrounding accumulation and persistence when applied in vivo. In this study, we developed protocols to extract and quantify SWNT from complex solutions and show an 89% sensor retention by hydrogel platforms when implanted in vivo. Animal tissues of interest were also extracted and probed for SWNT content showing no accumulation (0.03 mg l−1 SWNT detection limit). The methods developed in this paper demonstrated one avenue for applying SWNT sensors in vivo without concern for accumulation.

Reusable and highly sensitive SERS immunoassay utilizing gold nanostars and a cellulose hydrogel-based platform.

The development of robust and sensitive point-of-care testing platforms is necessary to improve patient care and outcomes. Surface-enhanced Raman scattering (SERS)-based immunosensors are especially suited for this purpose. Here, we present a highly sensitive and selective SERS immunoassay, demonstrating for example the detection of horseradish peroxidase (HRP), in a sandwich format. The strength of our biosensor lies in merging: (i) SERS-immunotags based on gold nanostars, allowing exceptional intense SERS from attached Raman probes, covalent attachment of anti-HRP antibodies by a simple chemical method providing exceptional antigen binding activity; (ii) the ease of preparation of the capture platform from a regenerated cellulose-based hydrogel, a transparent material, ideal for microfluidics applications, with low background fluorescence and Raman signal, particularly suited for preserving high activity of the covalently bound anti-HRP antibodies. The sandwich complexes formed were characterised by atomic force microscopy, and by scanning electron microscopy coupled with electron diffraction spectroscopy; and (iii) the robustness of the simple Classical Least Squares method for SERS data analysis, resulting in superior discrimination of SERS signals from the background and much better data fitting, compared to the commonly used peak integral method. Our SERS immunoassay greatly improves the detection limits of traditional enzyme-linked immunosorbent assay approaches, and its performance is better or comparable to those of existing SERS-based immunosensors. Our approach successfully overcomes the main challenges of application at point-of-care, including increasing reproducibility, sensitivity, and specificity, associated with an environmentally friendly and robust design. Also, the proposed design withstands several cycles of regeneration, a feature absent in paper-SERS immunoassays and this opens the way for sensitive multiplexing applications on a microfluidic platform.

Control of fibroblast shape in sequentially formed 3D hybrid hydrogels regulates cellular responses to microenvironmental cues

Cell shape plays important roles in regulating cell behavior; however, independently controlling cell shape in three dimensions is a challenging undertaking, and how cell shape affects cellular responses to mechanical and biochemical cues in three dimensions remains unclear. Here, we present a hydrogel-based platform to control cell shape in three dimensions by using sequentially formed hybrid hydrogels consisting of collagen and alginate. By adjusting the cross-linking time of the alginate, we fixed the shape of NIH 3T3 fibroblasts at different spreading states. Then, we explored the influence of cell shape on the cell responses to microenvironmental cues by using cardiac fibroblasts (CFs) as model cells. We found that the spreading state of the CFs influences their responses to both mechanical (i.e., matrix stiffness) and biochemical (i.e., transforming growth factor-β1 (TGF-β1)) cues in three dimensions. Additional experiments revealed that integrin β1 in focal adhesions and Smad2/3 are involved in mediating the cell shape-dependent responses of CFs to matrix stiffness and TGF-β1 cues, respectively. This work represents the first step in understanding how cell shape influences cell responses to mechanical and biochemical cues in three dimensions and can be instructive for developing novel approaches to target cell shape regulation for treating fibrosis and other diseases.

An in vitro hyaluronic acid hydrogel based platform to model dormancy in brain metastatic breast cancer cells

Breast cancer cells (BCCs) can remain dormant at the metastatic site, which when revoked leads to formation of metastasis several years after the treatment of primary tumor. Particularly, awakening of dormant BCCs in the brain results in breast cancer brain metastasis (BCBrM) which marks the most advanced stage of the disease with a median survival period of ~4–16 months. However, our understanding of dormancy associated with BCBrM remains obscure, in part, due to the lack of relevant in vitro platforms to model dormancy associated with BCBrM. To address this need, we developed an in vitro hyaluronic acid (HA) hydrogel platform to model dormancy in brain metastatic BCCs via exploiting the bio-physical cues provided by HA hydrogels while bracketing the normal brain and metastatic brain malignancy relevant stiffness range. In this system, we observed that MDA-MB-231Br and BT474Br3 brain metastatic BCCs exhibited a dormant phenotype when cultured on soft (0.4 kPa) HA hydrogel compared to stiff (4.5 kPa) HA hydrogel as characterized by significantly lower EdU and Ki67 positivity. Further, we demonstrated the nuclear localization of p21 and p27 (markers associated with dormancy) in dormant MDA-MB-231Br cells contrary to their cytoplasmic localization in the proliferative population. We also demonstrated that the stiffness-based dormancy in MDA-MB-231Br cells was reversible and was, in part, mediated by focal adhesion kinases and the initial cell seeding density. Finally, RNA sequencing confirmed the dormant phenotype in MDA-MB-231Br cells. This platform could further our understanding of dormancy in BCBrM and could be adapted for anti-metastatic drug screening. Statement of SignificanceOur understanding of dormancy associated with BCBrM remains obscure, in part, due to the lack of relevant in vitro platforms to model dormancy associated with BCBrM. Herein, we present a HA hydrogel-based platform to model dormancy in brain metastatic BCCs while recapitulating key aspects of brain microenvironment. We demonstrated that the biophysical cues provided the HA hydrogel mediates dormancy in brain metastatic BCCs by assessing both proliferation and cell cycle arrest markers. We also established the role of focal adhesion kinases and initial cell seeding density in the stiffness-mediated dormancy in brain metastatic BCCs. Further, RNA-seq. confirmed the dormant phenotype in brain metastatic BCCs. This platform could be utilized to further our understanding of microenvironmental regulation of dormancy in BCBrM.

Hydrogel-based platforms to mimic in vivo drug diffusion: A multicenter research

An airway mucus model is proposed thus serving as an in vitro screening tool with the aim to reduce the number of noneffective drugs reaching the preclinical trials. The engineered mucus model is an easy-to-use and easy-to-produce tool that can be easily coupled to state-of-art diffusion models and it is compatible with high throughput analysis. This platform will serve as the basis to implement the complexity of the model in terms of components, also including the effect of bacteria

Enhanced chondrogenic phenotype of primary bovine articular chondrocytes in Fibrin-Hyaluronan hydrogel by multi-axial mechanical loading and FGF18

Current treatments for cartilage lesions are often associated with fibrocartilage formation and donor site morbidity. Mechanical and biochemical stimuli play an important role in hyaline cartilage formation. Biocompatible scaffolds capable of transducing mechanical loads and delivering bioactive instructive factors may better support cartilage regeneration.In this study we aimed to test the interplay between mechanical and FGF-18 mediated biochemical signals on the proliferation and differentiation of primary bovine articular chondrocytes embedded in a chondro-conductive Fibrin-Hyaluronan (FB/HA) based hydrogel.Chondrocytes seeded in a Fibrin-HA hydrogel, with or without a chondro-inductive, FGFR3 selective FGF18 variant (FGF-18v) were loaded into a joint-mimicking bioreactor applying controlled, multi-axial movements, simulating the natural movements of articular joints. Samples were evaluated for DNA content, sulphated glycosaminoglycan (sGAG) accumulation, key chondrogenic gene expression markers and histology.Under moderate loading, samples produced particularly significant amounts of sGAG/DNA compared to unloaded controls. Interestingly there was no significant effect of FGF-18v on cartilage gene expression at rest. Following moderate multi-axial loading, FGF-18v upregulated the expression of Aggrecan (ACAN), Cartilage Oligomeric Matrix Protein (COMP), type II collagen (COL2) and Lubricin (PRG4). Moreover, the combination of load and FGF-18v, significantly downregulated Matrix Metalloproteinase-9 (MMP-9) and Matrix Metaloproteinase-13 (MMP-13), two of the most important factors contributing to joint destruction in OA. Biomimetic mechanical signals and FGF-18 may work in concert to support hyaline cartilage regeneration and repair. Statement of significanceArticular cartilage has very limited repair potential and focal cartilage lesions constitute a challenge for current standard clinical procedures. The aim of the present research was to explore novel procedures and constructs, based on biomaterials and biomechanical algorithms that can better mimic joints mechanical and biochemical stimulation to promote regeneration of damaged cartilage.Using a hydrogel-based platform for chondrocyte 3D culture revealed a synergy between mechanical forces and growth factors. Exploring the mechanisms underlying this mechano-biochemical interplay may enhance our understanding of cartilage remodeling and the development of new strategies for cartilage repair and regeneration.

Near-infrared light-controllable on-demand antibiotics release using thermo-sensitive hydrogel-based drug reservoir for combating bacterial infection

A near-infrared (NIR) light-triggerable thermo-sensitive hydrogel-based drug reservoir that can realize on-demand antibiotics release and hyperthermia-assisted bacterial inactivation was prepared to combat bacterial infection and promote wound healing. The drug reservoir was fabricated by mixing ciprofloxacin (Cip, a potent antibiotic)-loaded polydopamine (PDA) nanoparticles (NPs) and glycol chitosan (GC) to form an injectable hydrogel (PDA NP-Cip/GC hydrogel, abbreviated as Gel-Cip). On the one hand, the positive charge of GC and the adsorbability of PDA NPs made bacteria be readily trapped on the surface of Gel-Cip. On the other hand, the Gel-Cip exhibited minimal leakage under physiological conditions, but could boost Cip release upon NIR light irradiation. Meanwhile, NIR light irradiation could activate the photothermal PDA NPs, and the generated local hyperthermia induced the destruction of the bacterial integrity, leading to bacterial inactivation in a synergistic way. Moreover, the exceptional bacterial killing activity and outstanding wound healing ability of the system were also verified by the S. aureus-infected mouse skin defect model. Taken together, the light-activatable hydrogel-based platform allows us to release antibiotics more precisely, eliminate bacteria more effectively, and inhibit bacteria-induced infections more persistently, which will advance the development of novel antibacterial agents and strategies.

Facile Fabrication of a Modular "Catch and Release" Hydrogel Interface: Harnessing Thiol-Disulfide Exchange for Reversible Protein Capture and Cell Attachment.

Surfaces engineered to "specifically capture" and "release on demand" analytes ranging from biomolecules to cells find niche applications in areas such as diagnostics and detection. Utilization of a disulfide-based linker as a building block allows fabrication of a novel hydrogel-based platform that incorporates a "catch and release" attribute. Hydrogels incorporating pyridyl disulfide groups as thiol-reactive handles were prepared by photopolymerization in the presence of a poly(ethylene glycol) (PEG)-based cross-linker. A range of bulk and micropatterned hydrogels with varying amounts of the reactive group were prepared using PEG-based monomers with different chain lengths. Thiol-containing molecules were conjugated to these hydrogels through the thiol-disulfide exchange reaction under ambient conditions with high efficiencies, as determined by UV-vis spectroscopy. Facile conjugation of a thiol-containing fluorescent dye, namely 4,4-difluoro-1,3,5,7-tetramethyl-8-[(10-mercapto)]-4-bora-3 a,4 a-diaza- s-indacene, was demonstrated, followed by its effective cleavage in the presence of dithiothreitol (DTT), a thiol-containing disulfide-reducing agent. Conjugation of a biotin-containing ligand onto the hydrogels allowed specific binding of protein extravidin when exposed to a mixture of extravidin and bovine serum albumin. The bound protein could be released from the hydrogel by simple exposure to a DTT solution. Likewise, hydrogels modified with a cell-adhesive peptide unit containing the RGD sequence acted as favorable substrates for cellular attachment. Incubation of these cell-attached hydrogel surfaces in a DTT-containing solution leads to facile detachment of cells from the surfaces, while retaining a high level of cell viability. It can be envisioned that the benign nature of these hydrogels, their facile fabrication, and modular functionalization will make them attractive platforms for many applications.

Highly efficient delivery of potent anticancer iminoquinone derivative by multilayer hydrogel cubes.

Many potent anticancer drugs are hydrophobic and lack tumor selectivity, which limits their application in cancer therapy. Although cubical hydrogels of poly(methacrylic acid) exhibit excellent biocompatibility and versatility, they have not been investigated for hydrophobic drug delivery due to poor mechanical stability and incompatibility between hydrophobic drugs and a hydrophilic hydrogel network. In this study, we provide a facile method to prepare a multilayer hydrogel-based platform with controlled nanostructure, cubical shape and redox-responsiveness for delivery of highly potent anticancer therapeutics, hydrophobic BA-TPQ. The BA-TPQ-hydrogel cubes have exceptional structural stability upon lyophilization which is advantageous for a long-term storage. The greatly enhanced trans-epithelial permeability and amplified anti-tumor activity of BA-TPQ are achieved by encapsulation in these hydrogel cubes. Furthermore, the anticancer BA-TPQ-hydrogel platform retains the selective activity of BA-TPQ to hepatocellular carcinoma cells. Overall, the produced BA-TPQ-hydrogel cubes demonstrate a high potential for clinical liver cancer therapy.