In Situ Generation and High Bioresistance of Trityl-based Semiquinone Methide Radicals Under Anaerobic Conditions in Cellular Systems.

Bioreduction of spin labels and polarizing agents (generally stable radicals) has been an obstacle limiting the in-cell applications of pulsed electron paramagnetic resonance (EPR) spectroscopy and dynamic nuclear polarization (DNP). In this work, we have demonstrated that two semiquinone methide radicals (OXQM⋅ and CTQM⋅) can be easily produced from the trityl-based quinone methides (OXQM and CTQM) via reduction by various reducing agents including biothiols and ascorbate under anaerobic conditions. Both radicals have relatively low pKa's and exhibit EPR single line signals at physiological pH. Moreover, the bioreduction of OXQM in three cell lysates enables quantitative generation of OXQM⋅ which was most likely mediated by flavoenzymes. Importantly, the resulting OXQM⋅ exhibited extremely high stability in the E.coli lysate under anaerobic conditions with 76- and 14.3-fold slower decay kinetics as compared to the trityl OX063 and a gem-diethyl pyrrolidine nitroxide, respectively. Intracellular delivery of OXQM into HeLa cells was also achieved by covalent conjugation with a cell-permeable peptide as evidenced by the stable intracellular EPR signal from the OXQM⋅ moiety. Owing to extremely high resistance of OXQM⋅ towards bioreduction, OXQM and its derivatives show great application potential in in-cell EPR and in-cell DNP studies for various cells which can endure short-term anoxic treatments.

Self-Propelled Structural Color Cylindrical Micromotors for Heavy Metal Ions Adsorption and Screening.

Water contamination resulting from heavy metal ions (HMIs) poses a severe threat to public health and the ecosystem. Attempts are tending to develop functional materials to realize efficient and intelligent adsorption of HMIs. Herein, self-propelled structural color cylindrical micromotors (SCCMs) with reversible HMIs adsorption capacity and self-reporting property are presented. The SCCMs are fabricated by using platinum nanoparticles (Pt NPs) tagged responsive hydrogel of carboxymethyl chitosan (CMC) and polyacrylamide (PAM) to asymmetrically replicate tubular colloidal crystal templates (TCCTs). Owing to the self-propelled motion of the SCCMs, the enhancive ion-motor interactions bring significantly improved decontamination efficiency. Moreover, it is demonstrated that the SCCMs can realize quick and naked-eye-visible self-reporting during the adsorption/desorption process based on their responsive structure color variation and superior adsorption capacity. Thus, it is anticipated that such intelligent SCCMs can significantly facilitate the evolution of sensing assays and diverse environmental fields.

A Biomimetic Optical Cardiac Fibrosis-on-a-Chip for High-Throughput Anti-Fibrotic Drug Screening.

Cardiac fibrosis has emerged as the primary cause of morbidity, disability, and even mortality in numerous nations. In light of the advancements in precision medicine strategies, substantial attention has been directed toward the development of a practical and precise drug screening platform customized for individual patients. In this study, we introduce a biomimetic cardiac fibrosis-on-a-chip incorporating structural color hydrogels (SCHs) to enable optical high-throughput drug screening. By cocultivating a substantial proportion of cardiac fibroblasts (CFBs) with cardiomyocytes on the SCH, this biomimetic fibrotic microtissue successfully replicates the structural components and biomechanical properties associated with cardiac fibrosis. More importantly, the structural color shift observed in the SCH can be indicative of cardiac contraction and relaxation, making it a valuable tool for evaluating fibrosis progression. By incorporating such fibrotic microtissue into a microfluidic gradient chip, we develop a biomimetic optical cardiac fibrosis-on-a-chip platform that accurately and efficiently screens potential anti-fibrotic drugs. These characteristics suggest that this microphysiological platform possesses the capability to establish a preclinical framework for screening cardiac drugs, and may even contribute to the advancement of precision medicine.

A Biomimetic Cardiac Fibrosis-on-a-Chip as a Visible Disease Model for Evaluating Mesenchymal Stem Cell-Derived Exosome Therapy.

Cardiac fibrosis acts as a serious worldwide health issue due to its prevalence in numerous forms of cardiac disease and its essential link to cardiac failure. Considering the efficiency of stem cell therapy for cardiac fibrosis, great efforts have been dedicated to developing accurate models for investigating their underlying therapeutic mechanisms. Herein we present an elaborate biomimetic cardiac fibrosis-on-a-chip based on Janus structural color film (SCF) to provide microphysiological visuals for stem cell therapeutic studies. By coculturing cardiomyocytes (CMs) and cardiac fibroblasts (FBs) on Janus SCF with fibrosis induction, the chip can recreate physiological intercellular crosstalk within the fibrotic microenvironment, elucidating the physiological alterations of fibrotic hearts. In particular, the Janus structural color film possesses superior perceptual capabilities for capturing and responding to a weak cardiac force, demonstrating synchronized structural color shifts. Based on these features, we have not only explored the dynamic relationship between color mapping and the evaluated disease phenotype but also demonstrated the self-reporting capacity of the cardiac fibrosis-on-a-chip for the assessment of mesenchymal stem cell-derived exosome therapy. These features suggest that such a chip can potentially facilitate the evolution of precision medicine strategies and create a protocol for preclinical cardiac drug screening.

Living microecological hydrogels for wound healing.

Chronic hard-to-heal wounds draw great attention worldwide, as their treatments are limited by infections and hypoxia. Inspired by the natural oxygen production capacity of algae and the competitive advantage of beneficial bacteria over other microbes, we presented a living microecological hydrogel (LMH) with functionalized Chlorella and Bacillus subtilis encapsulation to realize continuous oxygen delivery and anti-infections for promoting chronic wound healing. As the hydrogel consisted of thermosensitive Pluronic F-127 and wet-adhesive polydopamine, the LMH could keep liquid at a low temperature while quickly solidifying and tightly adhering to the wound bed. It was demonstrated that by optimizing the proportion of the encapsulated microorganism, the Chlorella could continuously produce oxygen to relieve hypoxia and support the proliferation of B. subtilis, while B. subtilis could eliminate the colonized pathogenic bacteria. Thus, the LMH substantially promoted the healing of infected diabetic wounds. These features make the LMH valuable for practical clinical applications.

Construction of cardiac fibrosis for biomedical research.

Cardiac remodeling is critical for effective tissue recuperation, nevertheless, excessive formation and deposition of extracellular matrix components can result in the onset of cardiac fibrosis. Despite the emergence of novel therapies, there are still no lifelong therapeutic solutions for this issue. Understanding the detrimental cardiac remodeling may aid in the development of innovative treatment strategies to prevent or reverse fibrotic alterations in the heart. Further combining the latest understanding of disease pathogenesis with cardiac tissue engineering has provided the conversion of basic laboratory studies into the therapy of cardiac fibrosis patients as an increasingly viable prospect. This review presents the current main mechanisms and the potential tissue engineering of cardiac fibrosis. Approaches using biomedical materials-based cardiac constructions are reviewed to consider key issues for simulating in vitro cardiac fibrosis, outlining a future perspective for preclinical applications.

Encoding microcarriers for biomedicine.

High throughput biological analysis has become an important topic in modern biomedical research and clinical diagnosis. The flow encoding scheme based on the encoding microcarriers provides a feasible strategy for the multiplexed biological analysis. Different encoding characteristics invest the microcarriers with different encoding mechanisms. Biosensor analysis, drug screening, cell culture, and the construction and evaluation of bionic organ chips can be realized by decoding the microcarriers and quantifying the detection signal intensity. In this review, the encoding strategy of microcarriers was divided into the optical and non-optical encoding approaches according to their encoding elements, and the research progress of the microcarrier encoding strategy was elaborated. Finally, we summarized the biomedical applications and predicted their future prospects.

Artificial Periosteum with Oriented Surface Nanotopography and High Tissue Adherent Property.

Massive periosteal defects often significantly impair bone regeneration and repair, which have become a major clinical challenge. Unfortunately, current engineered periosteal materials can hardly currently focus on achieving high tissue adhesion property, being suitable for cell growth, and inducing cell orientation concurrently to meet the properties of nature periosteum. Additionally, the preparation of oriented surface nanotopography often relies on professional equipment. In this study, inspired by the oriented collagen structure of nature periosteum, we present a composite artificial periosteum with a layer of oriented nanotopography surface containing carbon nanotubes (CNTs), cross-linked with adhesive polydopamine (PDA) hydrogel on both terminals. An oriented surface structure that can simulate the oriented alignment of periosteal collagen fibers can be quickly and conveniently obtained via a simple stretching of the membrane in a water bath. With the help of CNTs, our artificial periosteum exhibits sufficient mechanical strength and desired oriented nanotopological structure surface, which further induces the directional arrangement of human bone marrow mesenchymal stem cells (hBMSCs) on the membrane. These oriented hBMSCs express significantly higher levels of osteogenic genes and proteins, while the resultant composite periosteum can be stably immobilized in vivo in the rat model of massive calvarial defect through the PDA hydrogel, which finally shows promising bone regeneration ability. We anticipate that the developed functional artificial periosteum has great potential in biomedical applications for the treatment of composite defects of the bone and periosteum.

Structural Color Medical Patch with Surface Dual-Properties of Wet Bioadhesion and Slipperiness.

Developing a self-reporting bioadhesive patch that has strong adhesion to the wet tissues and meanwhile can avoid adhering to the adjacent tissues is a current research difficulty and challenge. In this paper, inspired by the wet adhesion of spider web, slippery surface of Nepenthes, and structural color phenomena of chameleons, a novel structural color medical patch with surface dual-properties of wet bioadhesion and slipperiness for internal tissue repair based on inverse opal scaffold is presented. The adhesive surface made by poly(acrylic acid)-polyethylene glycol-N-hydroxysuccinimide ester and gelatin hydrogel can attain tough adhesion to internal wet tissues by absorbing tissue interfacial water and the covalent cross-linking between the hydrogel and tissue. Besides, the slippery surface made by liquid paraffin infused inverse opal scaffold can avoid adhesion to the adjacent tissues. It is demonstrated that the designed patch can adhere tightly to the defect tissue and improve the tissue repair without adjacent adhesion when applied in a rat model with full-thickness perforation of the stomach wall. In addition, the responsive structural color can supply a color-sensing monitoring to evaluate the adhesive and repair process. These features impart the bioinspired patch with great scientific significance and broad clinical application prospects.

A Biomimetic Human Lung-on-a-Chip with Colorful Display of Microphysiological Breath.

Lung-on-a-chip models hold great promise for disease modeling and drug screening. Herein, inspired by the iridescence phenomenon of soap bubbles, a novel biomimetic 3D microphysiological lung-on-a-chip system with breathing visualization is presented. The system, with an array of pulmonary alveoli at the physiological scale, is constructed and coated with structural color materials. Cyclic deformation is induced by regular airflow, resembling the expansion and contraction of the alveoli during rhythmic breathing. As the deformation is accompanied with corresponding synchronous shifts in the structural color, the constructed system offers self-reporting of the cell mechanics and enables real-time monitoring of the cultivation process. Using this system, the dynamic relationships between the color atlas and disease symptoms, showing the essential role of mechanical stretching in the phenotypes of idiopathic pulmonary fibrosis, are investigated. These features make this human lung system ideal in biological study, disease monitoring, and drug discovery.

Oriented Neural Spheroid Formation and Differentiation of Neural Stem Cells Guided by Anisotropic Inverse Opals.

Isotropic inverse opal structures have been extensively studied for the ability to manipulate cell behaviors such as attachment, migration, and spheroid formation. However, their use in regulate the behaviors of neural stem cells has not been fully explored, besides, the isotropic inverse opal structures usually lack the ability to induce the oriented cell growth which is fundamental in neural regeneration based on neural stem cell therapy. In this paper, the anisotropic inverse opal substrates were obtained by mechanically stretching the poly (vinylidene fluoride) (PVDF) inverse opal films. The anisotropic inverse opal substrates possessed good biocompatibility, optical properties and anisotropy, provided well guidance for the formation of neural spheroids, the alignment of neural stem cells, the differentiation of neural stem cells, the oriented growth of derived neurons and the dendritic complexity of the newborn neurons. Thus, we conclude that the anisotropic inverse opal substrates possess great potential in neural regeneration applications.

Porous Polyvinylidene Fluoride Thin-Film Sensors from Colloidal Crystal Templates.

With the development of the materials science, biosensors tend to be thin, flexible, versatile, and are extensively employed in biotechnology, clinical diagnosis, biochips, etc. However, most existing biosensors are single-functionalized and destitute in contrivable microstructure, which result in some inherent limitations. In this work, a novel thin-film sensor that had dual response generated from one stimulus was designed based on the colloidal crystal templates and devisable circuit system. Benefiting from designed platinum coating, the thin-film appeared as a flexible strain sensor which presented corresponding resistance changes with the slight deformation of the thin-film. In addition, with the sacrificial template method, the porous thin-film derived from the colloidal crystal template was endowed with manageable porous structure and splendid structural color, and the resultant color could be various when the environment changed. These features laid the foundation for the construction of multifunctional thin-film biosensor and presented potential applicability for a variety of biological research and flexible sensing devices.

Cardiomyocytes-Actuated Morpho Butterfly Wings.

Morpho butterflies are famous for their wings' brilliant structural colors arising from periodic nanostructures, which show great potential value for fundamental research and practical applications. Here, a novel cellular mechanical visualizable biosensor formed by assembling engineered cardiac tissues on the Morpho butterfly wings is presented. The assembled cardiomyocytes benefit from the periodic parallel nanoridges of the wings and can recover their autonomic beating ability with guided cellular orientation and good contraction performance. As the beating processes are accompanied by the cardiomyocytes' elongation and contraction, the elastic butterfly wing substrate undergoes the same cycle of deformations, which causes corresponding synchronous shifts in their structural colors and photonic bandgaps for self-reporting of the cell mechanics. It is demonstrated that this self-reporting performance can be further improved by adding oriented carbon nanotubes in the nanoridges of the wings for the culture. In addition, taking advantage of the similar size of the cardiomyocyte and a single Morpho wing scale, the investigation of single-cell-level mechanics can be realized by detecting the optical performance of a single scale. These remarkable properties make these butterfly wings ideal platforms for biomedical research.

Cardiomyocyte-Driven Structural Color Actuation in Anisotropic Inverse Opals.

Biohybrid actuators composed of living tissues and artificial materials have attracted increasing interest in recent years because of their extraordinary function of dynamically sensing and interacting with complex bioelectrical signals. Here, a compound biohybrid actuator with self-driven actuation and self-reported feedback is designed based on an anisotropic inverse opal substrate with periodical elliptical macropores and a hydrogel filling. The benefit of the anisotropic surface topography and high biocompatibility of the hydrogel is that the planted cardiomyocytes could be induced into a highly ordered alignment with recovering autonomic beating ability on the elastic substrate. Because of the cell elongation and contraction during cardiomyocyte beating, the anisotropic inverse opal substrates undergo a synchronous cycle of deformation actuations, which can be reported as corresponding shifts of their photonic band gaps and structural colors. These self-driven biohybrid actuators could be used as elements for the construction of a soft-bodied structural color robot, such as a biomimetic guppy with a swinging tail. Besides, with the integration of a self-driven biohybrid actuator and microfluidics, the advanced heart-on-a-chip system with the feature of microphysiological visuality has been developed for integrated cell monitoring and drug testing. This anisotropic inverse opal-derived biohybrid actuator could be widely applied in biomedical engineering.

Dechlorination of Hexachlorobenzene in Contaminated Soils Using a Nanometallic Al/CaO Dispersion Mixture: Optimization through Response Surface Methodology.

Hexachlorobenzene (HCB) contamination of soils remains a significant environmental challenge all over the world. Reductive stabilization is a developing technology that can decompose the HCB with a dechlorination process. A nanometallic Al/CaO (n-Al/CaO) dispersion mixture was developed utilizing ball-milling technology in this study. The dechlorination efficiency of HCB in contaminated soils by the n-Al/CaO grinding treatment was evaluated. Response surface methodology (RSM) was employed to investigate the effects of three variables (soil moisture content, n-Al/CaO dosage and grinding time) and the interactions between these variables under the Box-Behnken Design (BBD). A high regression coefficient value (R² = 0.9807) and low p value (<0.0001) of the quadratic model indicated that the model was accurate in predicting the experimental results. The optimal soil moisture content, n-Al/CaO dosage, and grinding time were found to be 7% (m/m), 17.7% (m/m), and 24 h, respectively, in the experimental ranges and levels. Under optimal conditions, the dechlorination efficiency was 80%. The intermediate product analysis indicated that dechlorination was the process by stepwise loss of chloride atoms. The main pathway observed within 24 h was HCB → pentachlorobenzene (PeCB) → 1,2,3,4-tetrachlorobenzene (TeCB) and 1,2,4,5-TeCB. The results indicated that the moderate soil moisture content was crucial for the hydrodechlorination of HCB. A probable mechanism was proposed wherein water acted like a hydrogen donor and promoted the hydrodechlorination process. The potential application of n-Al/CaO is an environmentally-friendly and cost-effective option for decontamination of HCB-contaminated soils.