Preparation and Application of Hemostatic Hydrogels.

Hemorrhage remains a critical challenge in various medical settings, necessitating the development of advanced hemostatic materials. Hemostatic hydrogels have emerged as promising solutions to address uncontrolled bleeding due to their unique properties, including biocompatibility, tunable physical characteristics, and exceptional hemostatic capabilities. In this review, a comprehensive overview of the preparation and biomedical applications of hemostatic hydrogels is provided. Particularly, hemostatic hydrogels with various materials and forms are introduced. Additionally, the applications of hemostatic hydrogels in trauma management, surgical procedures, wound care, etc. are summarized. Finally, the limitations and future prospects of hemostatic hydrogels are discussed and evaluated. This review aims to highlight the biomedical applications of hydrogels in hemorrhage management and offer insights into the development of clinically relevant hemostatic materials.

Multiple Bio-Actives Loaded Gellan Gum Microfibers from Microfluidics for Wound Healing.

Wound healing, known as a fundamental healthcare issue worldwide, has been attracting great attention from researchers. Here, novel bioactive gellan gum microfibers loaded with antibacterial peptides (ABPs) and vascular endothelial growth factor (VEGF) are proposed for wound healing by using microfluidic spinning. Benefitting from the high controllability of microfluidics, bioactive microfibers with uniform morphologies are obtained. The loaded ABPs are demonstrated to effectively act on bacteria at the wound site, reducing the risk of bacterial infection. Besides, sustained release of VEGF from microfibers helps to accelerate angiogenesis and further promote wound healing. The practical value of woven bioactive microfibers is demonstrated via animal experiments, where the wound healing process is greatly facilitated because of the excellent circulation of air and nutritious substances. Featured with the above properties, it is believed that the novel bioactive gellan gum microfibers would have a remarkable effect in the field of biomedical application, especially in promoting wound healing.

Near-Infrared Responsive Droplet for Digital PCR.

Digital PCR (dPCR) surpasses the performance of earlier PCR formats because of highly precise, absolute quantification and other unique merits. A simple thermocycling approach and durable microcarrier are of great value for dPCR advancement and application. Herein, a near-infrared (NIR) controlled thermocycling approach by embedding magnetic graphene oxide (GO) composite into the agarose microcarriers is developed. The core-shell composite is constructed by sequentially encapsulating GO and silica outside the magnetic nanocores. Benefiting from these additives, the resultant composite agarose gains appealing features as light-driven temperature changing, switchable gel-sol phase transforming, biocompatibility, and magnetic traction. By further emulsifying into droplets via the microfluidics method, the influence of typical parameters including material loading amount, laser intensity, and droplet diameter at various ranges is investigated for assembling microcarriers with different responsiveness. Then a paradigm of the NIR program can be easily tailored for PCR thermocycling. Finally, the feasibility of the approach is verified by detecting statistically diluted Klebsiella pneumoniae DNA samples, from 0.1 to 2 copies per drop. It is anticipated that this method has promising prospects for dPCR-based and other temperature-controlled applications.

Programmable Knot Microfibers from Piezoelectric Microfluidics.

Microfibers have demonstrated significant application values in a large number of areas. Current efforts focus on developing new technologies to prepare microfibers with controllable morphological and structural features to enhance their functions. Here, a piezoelectric microfluidic platform is presented for consecutive spinning of functional microfibers with programmable spindle-knots. In this platform, a jet of a pregel-solution flowing in the channel can be subjected to a programmable piezoelectric signal and vibrates synchronously. Following a rapid polymerization of the wavy jet, microfibers with corresponding morphologies can be generated, including uniform, gradient, and symmetrical knots. Such a unique knot structure contributes to a water-collection mechanism. Thus, it has been observed that microfibers with programmed knots enable even more flexible droplet handling and active water transport. In addition, by constructing higher-order knot fiber networks, practical applications including spray reaction, lab-on-a-chip vapor detection, etc., can also be demonstrated. it is believed that this platform opens a new avenue for fiber spinning, and the programmable microfibers would be highly applicable in chemical, biomedical, and environmental areas.

Biohybrid robotics with living cell actuation.

As simulators of organisms in Nature, soft robots have been developed over the past few decades. In particular, biohybrid robots constructed by integrating living cells with soft materials demonstrate the unique advantage of simulating the construction and functions of human tissues or organs, thus attracting extensive attention and research interest. Here, we present up-to-date studies concerning biohybrid robots with various biological actuators such as contractile cells and microorganisms. After presenting the basic components including biological components and synthetic materials, the controlling methods and locomotion modalities of biohybrid robots are clarified and summarized. We then focus on the applications, especially the biomedical applications, of the biohybrid robots including drug delivery, bioimaging, and tissue engineering. The challenges and prospects for the future development of biohybrid robots are also presented.

Cold-Responsive Nanocapsules Enable the Sole-Cryoprotectant-Trehalose Cryopreservation of ß Cell-Laden Hydrogels for Diabetes Treatment.

Islet transplantation has been one promising strategy in diabetes treatment, which can maintain patient's insulin level long-term and avoid periodical insulin injections. However, donor shortage and temporal mismatch between donors and recipients has limited its widespread use. Therefore, searching for islet substitutes and developing efficient cryopreservation technology (providing potential islet bank for transplantation on demand) is in great need. Herein, a novel cryopreservation method is developed for islet ß cells by combining microfluidic encapsulation and cold-responsive nanocapsules (CR-NCs). The cryopreserved cell-laden hydrogels (calcium alginate hydrogel, CAH) can be transplanted for diabetes treatment. During the freezing process, trehalose is released inside ß cells through the CR-NCs and serves as the sole cryoprotectant (CPA). Additionally, CAH helps cells to survive the freeze-thaw process and provide cells with a natural immune barrier in vivo. Different from traditional cryopreservation methods, this method combining the CR-NCs and hydrogel encapsulation replaces the toxic CPAs with natural trehalose. Great preservation results are obtained and transplantation experiments of diabetic rats further prove the excellent glucose regulation ability of such ß cell-laden hydrogels post cryopreservation. This novel cryopreservation method helps to establish a reliable and ready-to-use bank of biological samples for transplantation therapy and other biomedical applications.

Conductive Polymer Hydrogel Microfibers from Multiflow Microfluidics.

Conductive hydrogels are receiving increasing attention for their utility in electronic area applications requiring flexible conductors. Here, it is presented novel conductive hydrogel microfibers with alginate shells and poly (3, 4-ethylenedioxythiophene): poly (4-styrenesulfonate) (PEDOT: PSS) cores fabricated using a multiflow capillary microfluidic spinning approach. Based on multiflow microfluidics, alginate shells are formed immediately from the fast gelation reaction between sodium alginate (Na-Alg) and sheath laminar calcium chloride flows, while PEDOT: PSS cores are solidified slowly in the hollow alginate hydrogel shell microreactors after their precursor solutions are injected in situ as the center fluids. The resultant PEDOT: PSS-containing microfibers are with features of designed morphology and highly controllable package, because material compositions or the sizes of their shell hydrogels can be tailored by using different concentrations or flow rates of pregel solutions. Moreover, the practical values of these microfibers in stretch sensitivity and bending stability are explored based on various electrical characterizations of the compound materials. Thus, it is believed that these microfluidic spinning PEDOT: PSS conductive microfibers will find important utility in electronic applications requiring flexible electronic systems.

Ononin, sec-O-ß-d-glucosylhamaudol and astragaloside I: antiviral lead compounds identified via high throughput screening and biological validation from traditional Chinese medicine Zhongjing formulary.

Traditional medicine (TM) is a valuable source for drug discovery. The knowledge in healing traditions has led to the success of some of the best-known drugs. However, the concept of ancient medical knowledge, such as herbal remedies and their therapeutic experience is rarely used in the current methodologies for developing therapeutics from TM. As a result, the screening procedure of TM compounds remains tough and labor-intensive. This study aimed to develop a new strategy that is capable of efficiently identifying antiviral leads from complex traditional Chinese medicine (TCM) by integrating knowledge from ancient healing practices with luciferase-based high-throughput screening (HTS). 'Shanghan Zabing Lun', an ancient TCM treatise which contains over 200 formulae was selected for knowledge mining based on its antiviral activity. Thirty formulae were rationally selected and utilized for the preparation of a 1306-fraction herbal formulae extract library by standardized chromatographic fractionation. The antiviral activity of the library was screened on a HEK293T cell model carrying a luciferase-driven interferon stimulated response element (ISRE). Hit compounds were further identified using liquid chromatography mass spectrometry analysis, and the mechanism of action of which were preliminarily explored through western blotting and immunofluorescence. A total of 18 fractions and 3 compounds were found activating ISRE. The three compounds, namely ononin, sec-O-ß-d-glucosylhamaudol and astragaloside I could activate p65 phosphorylation and nuclear translocation. By doing so, a new strategy termed Knowledge-Based High Throughput Screening (KB-HTS) has been established, which provides an alternative approach to unearth antiviral lead compounds from TM. This new discovery pipeline can expedite the discovery process by improving dereplication and lead prioritization strategies, which is valuable for novel lead discovery from traditional medicine.

Microfluidic Generation of Bioinspired Spindle-knotted Graphene Microfibers for Oil Absorption.

Graphene materials have a demonstrated value in water treatment. Efforts to promote these materials are focused on the generation of functional graphene adsorbents for effectively removing contaminants from water. Here, inspired by the conformation of spider silks, we present a novel graphene microfiber material with spindle-knotted microstructures by using a microfluidic emulsification and spinning collaborative technology. The size and spacing of the spindle-knots were highly controllable by adjusting the flow rates of microfluidics during the generation process of the microfibers. The generated microfibers could adsorb oil from a water-oil mixed environment due to their hydrophobic surface chemistry. Because of the surface energy curvature gradient and the difference in Laplace pressure, the collected oil tended to form droplets and move from joints between the spindle-knots to the knots. In addition, by encapsulating additional functional elements, such as magnetic nanoparticles, the graphene microfiber with the ability to control and facilitate the collection of oily contaminants can also be achieved. These features greatly prove the promising values of the spindle-knotted graphene microfibers in the protection of the environment.

Bioinspired Multifunctional Spindle-Knotted Microfibers from Microfluidics.

Heterostructured microfibers with spindle-knots and joints are developed using a novel microfluidic technology, which enables integrative microfiber joint spinning, fluid coating, and knot emulsification. The knots emulsification process can be precisely tunable by adjusting the flow rates. In this way, the size and spacing of the spindle-knots of the microfibers can be achieved with high controllability. More attractively, the construction process benefits from the broad availability of the coating fluids, which determines the compositions of the knots. Thus, the resultant microfibers are imparted with distinctive functions, such as humidity-responsive water capture, thermally triggered water convergence, induced colloidal crystal assembly, and cell microcarrier arrays. These features make such microfibers highly versatile for use in diverse applications.

[Establishment pharmacological research platform for "Concurrent treatment of the brain and heart" and its application on dissecting mechanism of Danhong injection].

The Concurrent treatment of the brain and heart (CTBH) theory is proposed based on traditional Chinese medical theory and clinical practice. In this study, a framework for the pharmacological research platform was established to investigate the principles of concurrent treatment of the brain and heart. The platform for CTBH includes several key techniques for network modeling, discovery of active substances, dissecting mechanism of action and investigation of pharmacokinetic property of TCM. Taking network modeling of CTBH as an example, using database search, literature mining, network construction and module analysis, the that network modules closely associated with the pathological progress of cardiovascular and cerebrovascular diseases were identified, while further functional enrichment analysis of these modules indicated that the key biological processes included oxidative stress, metabolism and inflammation. GSK3B, NOTCH1, CDK4 were identified as key nodes in these network modules. The above-mentioned platform was applied to construct component-biomolecules network of Danhong injection for the identification of common targets and pathways. Among them, GSK3B had the highest correlation with the composition of Danhong injection in the network, and the biological function of whose cluster was related to cell oxidative stress. Based upon results of network analysis, validation experiments suggested that Danhong injection significantly improved the survival rate of oxidative injured myocardial cells and nerve cells, and the protective effect was related to the increase of phosphorylated GSK3ß protein expression. Moreover, extracts of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos exerted the synergisticcytoprotective effect. The results indicated that the mechanism of treatment of cardiovascular and cerebrovascular diseases of Danhong injection could be studied through network modeling and other methods. In summary, the proposed pharmacological platform provided a feasible way for revealing the mechanism of CTBH by using modern scientific methods.

Microfluidic Lithography of Bioinspired Helical Micromotors.

Considerable efforts have been devoted to developing artificial micro/nanomotors that can convert energy into movement. A flow lithography integrated microfluidic spinning and spiraling system is developed for the continuous generation of bioinspired helical micromotors. Because the generation processes could be precisely tuned by adjusting the flow rates and the illuminating frequency, the length, diameter, and pitch of the helical micromotors were highly controllable. Benefiting from the fast online gelation and polymerization, the resultant helical micromotors could be imparted with Janus, triplex, and core-shell cross-sectional structures that have never been achieved by other methods. Owing to the spatially controlled encapsulation of functional nanoparticles in the microstructures, the helical micromotors can perform locomotion not only by magnetically actuated rotation or corkscrew motion but also through chemically powered catalytic reaction.

Hydrogel-Encapsulated Pancreatic Islet Cells as a Promising Strategy for Diabetic Cell Therapy.

Islet transplantation has now become a promising treatment for insulin-deficient diabetes mellitus. Compared to traditional diabetes treatments, cell therapy can restore endogenous insulin supplementation, but its large-scale clinical application is impeded by donor shortages, immune rejection, and unsuitable transplantation sites. To overcome these challenges, an increasing number of studies have attempted to transplant hydrogel-encapsulated islet cells to treat diabetes. This review mainly focuses on the strategy of hydrogel-encapsulated pancreatic islet cells for diabetic cell therapy, including different cell sources encapsulated in hydrogels, encapsulation methods, hydrogel types, and a series of accessorial manners to improve transplantation outcomes. In addition, the formation and application challenges as well as prospects are also presented.

Sprayable Multifunctional Black Phosphorus Hydrogel with On-Demand Removability for Joint Skin Wound Healing.

Wound healing remains a critical challenge in regenerative engineering. Great efforts are devoted to develop functional patches for wound healing. Herein, a novel sprayable black phosphorus (BP)-based multifunctional hydrogel with on-demand removability is presented as a joints' skin wound dressing. The hydrogel is facilely prepared by mixing dopamine-modified oxidized hyaluronic acid, cyanoacetategroup-functionalized dextran containing black phosphorus, and the catalyst histidine. The catechol-containing dopamine can not only enhance tissue adhesiveness, but also endow the hydrogel with antioxidant capacity. In addition, benefiting from the photothermal conversion ability of the BP and thermally reversible performance of the formed C═C double bonds between aldehyde groups and cyanoacetate groups, the resulting hydrogel displays excellent antibacterial performance and on-demand dissolving ability under NIR irradiation. Moreover, by loading vascular endothelial growth factor into the hydrogel, the promoted migration and angiogenesis effects of endothelial cells can also be achieved. Based on these features, it is demonstrated that such sprayable BP hydrogels can effectively facilitate joint wounds healing by accelerating angiogenesis, alleviating inflammation, and improving wound microenvironment. Thus, it is believed that this NIR-responsive removable BP hydrogel dressing will put forward an innovative concept in designing wound dressings.

Biopolymer-Assembled Porous Hydrogel Microfibers from Microfluidic Spinning for Wound Healing.

Hydrogels are considered as a promising medical patch for wound healing. Researches in this aspect are focused on improving their compositions and permeability to enhance the effectiveness of wound healing. Here, novel prolamins-assembled porous hydrogel microfibers with the desired merits for treating diabetes wounds are presented. Such microfibers are continuously generated by one-step microfluidic spinning technology with acetic acid solution of prolamins as the continuous phase and deionized water as the dispersed phase. By adjusting the prolamin concentration and flow rates of microfluidics, the porous structure and morphology as well as diameters of microfibers can be well tailored. Owing to their porosity, the resultant microfibers can be employed as flexible delivery systems for wound healing actives, such as bacitracin and vascular endothelial growth factor (VEGF). It is demonstrated that the resultant hydrogel microfibers are with good cell-affinity and effective drug release efficiency, and their woven patches display superior in vivo capability in treating diabetes wounds. Thus, it is believed that the proposed prolamins-assembled porous hydrogel microfibers will show important values in clinic wound treatments.

Bioinspired Jellyfish Microparticles from Microfluidics.

Nonspherical particles have attracted increasing interest because of their shape anisotropy. However, the current methods to prepare anisotropic particles suffer from complex generation processes and limited shape diversity. Here, we develop a piezoelectric microfluidic system to generate complex flow configurations and fabricate jellyfish-like microparticles. In this delicate system, the piezoelectric vibration could evolve a jellyfish-like flow configuration in the microchannel and the in situ photopolymerization could instantly capture the flow architecture. The sizes and morphologies of the particles are precisely controlled by tuning the piezoelectric and microfluidic parameters. Furthermore, multi-compartmental microparticles with a dual-layer structure are achieved by modifying the injecting channel geometry. Moreover, such unique a shape endows the particles with flexible motion ability especially when stimuli-responsive materials are incorporated. On the basis of that, we demonstrate the capability of the jellyfish-like microparticles in highly efficient adsorption of organic pollutants under external control. Thus, it is believed that such jellyfish-like microparticles are highly versatile in potential applications and the piezoelectric-integrated microfluidic strategy could open an avenue for the creation of such anisotropic particles.

Cryo-shocked cancer cell microgels for tumor postoperative combination immunotherapy and tissue regeneration.

Prevention of recurrence/metastasis and tissue regeneration are critical for post-surgery treatment of malignant tumors. Here, to address these needs, a novel type of microgel co-loading cryo-shocked cancer cells, immunoadjuvant, and immune checkpoint inhibitor is presented by microfluidic electrospray technology and liquid nitrogen treatment. Owing to the encapsulation of cryo-shocked cancer cells and immunoadjuvant, the microgels can recruit dendritic cells and activate them in situ, and evoke a robust immune response. Moreover, with the combination of the immune checkpoint inhibitor, the antitumor immune response is further enhanced by inhibiting the interaction of PD1 and PDL1. With this, the excellent anti-recurrence and anti-metastasis efficacy of the microgels are demonstrated in an orthotopic breast cancer mouse model. Besides, because of the excellent biocompatibility and appropriate degradation performance, the microgels can provide support for normal cell adhesion and growth, which is beneficial to tissue reconstruction. These properties indicate the great value of the cryo-shocked cancer cell microgels for efficient tumor postoperative combination immunotherapy and tissue regeneration.

Pearl Powder Hybrid Bioactive Scaffolds from Microfluidic 3D Printing for Bone Regeneration.

The development of bioactive scaffolds by mimicking bone tissue extracellular matrix is promising for bone regeneration. Herein, inspired by the bone tissue composition, a novel pearl powder (PP) hybrid fish gelatin methacrylate (GelMa) hydrogel scaffold loaded with vascular endothelial growth factor (VEGF) for bone regeneration is presented. With the help of microfluidic-assisted 3D printing technology, the composition and structure of the hybrid scaffold can be accurately controlled to meet clinical requirements. The combination of fish skin GelMa and PP also endowed the hybrid scaffold with good biocompatibility, cell adhesion, and osteogenic differentiation ability. Moreover, the controlled release of VEGF enables the scaffold to promote angiogenesis. Thus, the bone regeneration in the proposed scaffolds could be accelerated under the synergic effect of osteogenesis and angiogenesis, which has been proved in the rat skull defect model. These features indicate that the PP hybrid scaffolds will be an ideal candidate for bone regeneration in clinical applications.

Multi-Bioinspired Functional Conductive Hydrogel Patches for Wound Healing Management.

Many hydrogel patches are developed to solve the pervasive and severe challenge of complex wound healing, while most of them still lack satisfactory controllability and comprehensive functionality. Herein, inspired by multiple creatures, including octopuses and snails, a novel muti-functional hydrogel patch is presented with controlled adhesion, antibacterial, drug release features, and multiple monitoring functions for intelligent wound healing management. The patch with micro suction-cup actuator array and a tensile backing layer is composed of tannin grafted gelatin, Ag-tannin nanoparticles, polyacrylamide (PAAm) and poly(N-isopropylacrylamide) (PNIPAm). In virtue of the photothermal gel-sol transition of tannin grafted gelatin and Ag-tannin nanoparticles, the patches exert a dual anti-microbial effect and temperature-sensitive snail mucus-like features. In addition, as the "suction-cups" consisting of thermal responsive PNIPAm can undergo a contract-relax transformation, the medical patches can adhere to the objects reversibly and responsively, and release their loaded vascular endothelial growth factor (VEGF) controllably for wound healing. More attractively, benefiting from their fatigue resistance, self-healing ability of the tensile double network hydrogel, and electrical conductivity of Ag-tannin nanoparticles, the proposed patches can report multiple wound physiology parameters sensitively and continuously. Thus, it is believed that this multi-bioinspired patch has immense potential for future wound healing management.