Bio-inspired biorthogonal compartmental microparticles for tumor chemotherapy and photothermal therapy.

Microcarrier is a promising drug delivery system demonstrating significant value in treating cancers. One of the main goals is to devise microcarriers with ingenious structures and functions to achieve better therapeutic efficacy in tumors. Here, inspired by the nucleus-cytoplasm structure of cells and the material exchange reaction between them, we develop a type of biorthogonal compartmental microparticles (BCMs) from microfluidics that can separately load and sequentially release cyclooctene-modified doxorubicin prodrug (TCO-DOX) and tetrazine-modified indocyanine green (Tz-ICG) for tumor therapy. The Tz-ICG works not only as an activator for TCO-DOX but also as a photothermal agent, allowing for the combination of bioorthogonal chemotherapy and photothermal therapy (PTT). Besides, the modification of DOX with cyclooctene significantly decreases the systemic toxicity of DOX. As a result, the developed BCMs demonstrate efficient in vitro tumor cell eradication and exhibit notable tumor growth inhibition with favorable safety. These findings illustrate that the formulated BCMs establish a platform for bioorthogonal prodrug activation and localized delivery, holding significant potential for cancer therapy and related applications.

3D Printing of Naturally Derived Adhesive Hemostatic Sponge.

Hydrogel hemostatic sponges have been recognized for its effectiveness in wound treatment due to its excellent biocompatibility, degradability, as well as multi-facet functionalities. Current research focuses on optimizing the composition and structure of the sponge to enhance its therapeutic effectiveness. Here, we propose an adhesive hydrogel made from purely natural substances extracted from okra and Panax notoginseng. We utilize 3-dimensional (3D) printing technology to fabricate the hemostatic hydrogel scaffold, incorporating gelatin into the hydrogel and refining the mixing ratio. The interaction between gelatin and okra polyphenols contributes to successful injectability as well as stability of the printed scaffold. The okra in the scaffold exhibits favorable adhesion and hemostatic effects, and the total saponins of Panax notoginseng facilitate angiogenesis. Through in vitro experiments, we have substantiated the scaffold's excellent stability, adhesion, biocompatibility, and angiogenesis-promoting ability. Furthermore, in vivo experiments have demonstrated its dual functionality in rapid hemostasis and wound repair. These features suggest that the 3D-printed, natural substance-derived hydrogel scaffolds have valuable potential in wound healing and related applications.

Stem cell recruitment polypeptide hydrogel microcarriers with exosome delivery for osteoarthritis treatment.

With the accelerated aging tendency, osteoarthritis (OA) has become an intractable global public health challenge. Stem cells and their derivative exosome (Exo) have shown great potential in OA treatment. Research in this area tends to develop functional microcarriers for stem cell and Exo delivery to improve the therapeutic effect. Herein, we develop a novel system of Exo-encapsulated stem cell-recruitment hydrogel microcarriers from liquid nitrogen-assisted microfluidic electrospray for OA treatment. Benefited from the advanced droplet generation capability of microfluidics and mild cryogelation procedure, the resultant particles show uniform size dispersion and excellent biocompatibility. Moreover, acryloylated stem cell recruitment peptides SKPPGTSS are directly crosslinked within the particles by ultraviolet irradiation, thus simplifying the peptide coupling process and preventing its premature release. The SKPPGTSS-modified particles can recruit endogenous stem cells to promote cartilage repair and the released Exo from the particles further enhances the cartilage repair performance through synergistic effects. These features suggest that the proposed hydrogel microcarrier delivery system is a promising candidate for OA treatment.

Magnetic Polysaccharide Mesenchymal Stem Cells Exosomes Delivery Microcarriers for Synergistic Therapy of Osteoarthritis.

Osteoarthritis (OA) is a prevalent degenerative disease that afflicts more than 250 million people worldwide, impairing their mobility and quality of life. However, conventional drug therapy is palliative. Exosomes (Exo), although with the potential to fundamentally repair cartilage, face challenges in their efficient enrichment and delivery. In this study, we developed magnetic polysaccharide hydrogel particles as microcarriers for synergistic therapy of OA. The microcarriers were composed of modified natural polysaccharides, hyaluronic acid (HAMA), and chondroitin sulfate (CSMA), and were generated from microfluidic electrospray in combination with a cryogelation process. Magnetic nanoparticles with spiny structures capable of capturing stem cell Exo were encapsulated within the microcarriers together with an anti-inflammatory drug diclofenac sodium (DS). The released DS and Exo from the microcarriers had a synergistic effect in alleviating the OA symptoms and promoting cartilage repair. The in vitro and in vivo results demonstrated the excellent performance of the microcarrier for OA treatment. We believe this work has potential for Exo therapy of OA and other related diseases.

Flexible liquid-diode microtubes from multimodal microfluidics.

Directional transport of liquids is of great importance in energy saving, chemical/biomedical engineering, and microfluidics applications. Despite considerable progress in engineering different open surfaces to achieve liquid manipulation, the realization of diode-like liquid transport in enclosed spaces is still challenging. Here, a flexible diode microtube is presented for directional liquid transport within confined spaces using pulsed microfluidics. The microtubes exhibit sophisticated microstructures on the inner wall, replicated from a precisely controlled flow configuration in the microfluidic channel. Under the effect of asymmetric pinning and unbalanced Laplace pressure, such microtubes enable directional liquid transport in closed channels. More importantly, by integrating in situ flow lithography with the microfluidic system, segmented liquid diodes are fabricated as assembly units for the construction of fluidic-electronic circuits that perform logic operations. These results demonstrate the capacity of the present liquid-diode microtubes for flexible, directional, and programmable liquid transport. We believe that it can open an avenue for designing advanced fluidic circuit-based devices toward versatile practical applications.

Self-Healing Dynamic Hydrogel Microparticles with Structural Color for Wound Management.

Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances. It is vital to develop multifunctional hydrogel dressings, with well-designed morphology and structure to enhance flexibility and effectiveness in wound management. To achieve these, we propose a self-healing hydrogel dressing based on structural color microspheres for wound management. The microsphere comprised a photothermal-responsive inverse opal framework, which was constructed by hyaluronic acid methacryloyl, silk fibroin methacryloyl and black phosphorus quantum dots (BPQDs), and was further re-filled with a dynamic hydrogel. The dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran (DEX-CA and DEX-BA). Notably, the composite microspheres can be applied arbitrarily, and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic hydrogel. Additionally, eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same mechanism. Moreover, effective monitoring of the drug release process can be achieved through visual color variations. The microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound management. These characteristics suggest broad prospects for the proposed composite microspheres in clinical applications.

Glucose Responsive Coacervate Protocells from Microfluidics for Diabetic Wound Healing.

The hyperglycemic pathophysiological environment in diabetic wounds is a major obstacle that impedes the healing process. Glucose-responsive wound healing materials are a promising approach to address this challenge. In this study, complex coacervate-based protocells are introduced for diabetic wound healing. By employing a microfluidic chip with an external mechanical vibrator, uniform coacervate microdroplets are generated via electrostatic interactions between diethylaminoethyl-dextran and double-stranded DNA. The spontaneous assembly of a phospholipid membrane on the droplet surface enhances its biocompatibility. Glucose oxidase and copper peroxide nanodots are integrated into microdroplets, enabling a glucose-responsive cascade that produces hydroxyl radicals as antibacterial agents. These features contribute to efficient antibacterial activity and wound healing in diabetic mice. The present protocells facilitate intelligent wound management, and the design of cascade catalytic coacervates can contribute to the development of various smart vehicles for drug delivery.

Microfluidic-based multifunctional microspheres for enhanced oral co-delivery of probiotics and postbiotics.

Probiotic-based therapies have shown great potential in the prevention and treatment of many diseases by positively regulating intestinal flora homeostasis. However, the efficacy of oral probiotics is severely limited due to the loss of bioactivity, short intestinal retention time, and insufficient therapeutic effect. Here, based on droplet microfluidics, we developed a hydrogel microsphere with colonic targeting and mucoadhesive capabilities as a multifunctional delivery platform, which can be used for co-delivery of probiotics (Escherichia coli Nissle 1917, EcN) and auxiliary molecules (indole-3-propionic acid, IPA), achieving synergistic therapeutic effects. In vivo studies shown that the integrated multifunctional microspheres can significantly reduce intestinal inflammation, repair intestinal barrier function, enhance probiotic colonization in the intestine, and modulate disordered intestinal flora, demonstrating enhanced therapeutic effects in a mouse model of colitis. This work reveals that microfluidic-based smart droplet microspheres can provide a versatile platform for advanced microbial therapies.

Microfluidics-derived hierarchical microparticles for the delivery of dienogest for localized endometriosis therapy.

Drug therapy is one of the most important strategies for treating gynecological diseases. Local drug delivery is promising for achieving optimal regional drug exposure, considering the complex anatomy and dynamic environment of the upper genital tract. Here, we present microparticle-based microcarriers with a hierarchical structure for localized dienogest (DNG) delivery and endometriosis treatment. The microparticles were fabricated by microfluidics and consisted of photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA (poly lactic-co-glycolic acid) microspheres. Such design enables the microparticles to have sustained release capacity and cell adhesion ability. Based on this, the microparticles were applied for the treatment of peritoneal endometriosis through intraperitoneal injection. The performance of the microparticles in inhibiting the growth of ectopic lesions as well as their anti-inflammatory, anti-angiogenesis, and pelvic pain-relieving effects are well demonstrated in vivo. These findings indicate that the present hierarchical microparticles are good candidates for localized treatment of endometriosis and are promising for the management of gynecological diseases. STATEMENT OF SIGNIFICANCE: We prepared photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA microspheres using microfluidic electrospray. Such hierarchical structure provided multiple functions of the particles as drug carriers. The hierarchical microparticles not only supported the sustained release of drugs but also provided adhesion to human ectopic endometrial stromal cells. The hierarchical microparticles represented a localized treatment method for endometriosis and is promising for the management of gynecological diseases.

Bioinspired Confined Assembly of Cellulosic Cholesteric Liquid Crystal Bubbles.

Construction of biomimetic models for structural color evolution not only gives new photonic phenomena but also provide cues for biological morphogenesis. Here, a novel confined self-assembly method is proposed for the generation of hydroxypropyl cellulose (HPC)-based cholesteric liquid crystals (CLCs) microbubbles. The assembly process relies on the combination of droplet microfluidics, solvent extraction, and a volume confined environment. The as-prepared HPC structural color microbubbles have a transparent shell, an orderly arranged cholesteric liquid crystal (CLC) middle layer, and an innermost bubble core. The size of the microbubble, shell thickness, and the color of the CLC layer can be adjusted by altering the microfluidic parameters. Intriguingly, benefited from the compartmentalization effect provided by droplet microfluidics, microbubbles with multiple cores of different color combinations are generated under precise control. The self-assembled CLCs microbubbles have bright structural color, suspending ability, and good temperature-sensitive characteristics, making them ideal underwater sensors. The present confined assembly approach will shed light on creating novel photonic structures and the HPC microbubble will find widespread applications in multifunctional sensing, optical display, and other related fields are believed.

Breadmaking-Inspired Antioxidant Porous Yeast Microcarriers for Stem Cell Delivery in Diabetic Wound Treatment.

Stem cell-based therapies have exhibited significant promise in the treatment of diabetic ulcers (DU). Nevertheless, enhancing the survival rate and functionality of transplanted stem cells poses a substantial challenge. In this study, inspired by the breadmaking process, yeast microcarriers (YMC) are devised as vehicles for stem cells to address these challenges. The fabrication of YMC involves the amalgamation of microfluidic emulsification with yeast-mediated fermentation, yielding microcarriers with outstanding biocompatibility, high porosity, and antioxidant activity. Adipose-derived stem cells (ADSCs) seeded onto YMC display remarkable cell viability and retain their cellular functions effectively. Additionally, YMC boast a rich glutathione content and exhibit remarkable ROS scavenging ability, thus shielding the ADSCs from oxidative stress. In vivo experiments further substantiate that ADSC@YMC implementation significantly lowered ROS levels in diabetic wounds, resulting in enhanced stem cell retention and improved angiogenesis, collagen deposition, and tissue regeneration. These results highlight the potential of ADSC@YMC as a promising platform for delivering stem cell in the treatment of diabetic wounds.

Photothermal Responsive Microcarriers Encapsulated With Cangrelor and 5-Fu for Colorectal Cancer Treatment.

Localized chemotherapy is emerging as a potential strategy for cancer treatment due to its low systemic toxicity. However, the immune evasion of tumor cells and the lack of an intelligent design of the delivery system limit its clinical application. Herein, photothermal responsive microcarriers are designed by microfluidic electrospray for colorectal tumor treatment. The microcarriers loaded with Cangrelor, 5-FU and MXene (G-M@F/C+NIR) show sustained delivery of antiplatelet drug Cangrelor, thus inhibiting the activity of platelets, interactions of platelet-tumor cell, as well as the tumor cells invasion and epithelial-mesenchymal transition (EMT). In addition, the sustained delivery of chemotherapeutics 5-FU and the photothermal effect provided by MXene enable the microcarriers to inhibit tumor cells proliferation and migration. In vivo studies validate that the G-M@F/C+NIR microcarriers significantly inhibites tumor growth, decreased the expression of Ki-67 in tumor cells and vascular endothelial growth factor (VEGF) in the tumor microenvironment, while increased the expression of E-cadherin. It is believe that by means of the proposed photothermal responsive microcarriers, the synergistic strategy of platelet inhibition, chemotherapy, and photothermal therapy can find practical applications in cancer treatment.

Multi-Bioinspired MOF Delivery Systems from Microfluidics for Tumor Multimodal Therapy.

Metal-organic framework (MOF)-based drug delivery systems have demonstrated values in oncotherapy. Current research endeavors are centralized on the functionality enrichment of featured MOF materials with designed versatility for synergistic multimodal treatments. Here, inspired by the multifarious biological functions including ferroptosis pattern, porphyrins, and cancer cell membrane (CCM) camouflage technique, novel multi-biomimetic MOF nanocarriers from microfluidics are prepared. The Fe3+ , meso-tetra(4-carboxyphenyl)porphine and oxaliplatin prodrug are incorporated into one MOF nano-system (named FeTPt), which is further cloaked by CCM to obtain a "Trojan Horse"-like vehicle (FeTPt@CCM). Owing to the functionalization with CCM, FeTPt@CCM can target and accumulate at the tumor site via homologous binding. After being internalized by cancer cells, FeTPt@CCM can be activated by a Fenton-like reaction as well as a redox reaction between Fe3+ and glutathione and hydrogen peroxide to generate hydroxyl radical and oxygen. Thus, the nano-platform effectively initiates ferroptosis and improves photodynamic therapy performance. Along with the Pt-drug chemotherapy, the nano-platform exhibits synergistic multimodal actions for inhibiting cancer cell proliferation in vitro and suppressing tumor growth in vivo. These features indicate that such a versatile biomimetic MOF delivery system from microfluidics has great potential for synergistic cancer treatment.

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.

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.

Liquid Crystal Materials for Biomedical Applications.

Liquid crystal is a state of matter being intermediate between solid and liquid. Liquid crystal materials exhibit both orientational order and fluidity. While liquid crystals have long been highly recognized in the display industry, in recent decades, liquid crystals provide new opportunities into the cross-field of material science and biomedicine due to their biocompatibility, multifunctionality, and responsiveness. In this review, the latest achievements of liquid crystal materials applied in biomedical fields are summarized. The start is made by introducing the basic concepts of liquid crystals, and then shifting to the components of liquid crystals as well as functional materials derived therefrom. After that, the ongoing and foreseeable applications of liquid crystal materials in the biomedical field with emphasis put on several cutting-edge aspects, including drug delivery, bioimaging, tissue engineering, implantable devices, biosensing, and wearable devices are discussed. It is hoped that this review will stimulate ingenious ideas for the future generation of liquid crystal-based drug development, artificial implants, disease diagnosis, health status monitoring, and beyond.

Rocket-Inspired Effervescent Motors for Oral Macromolecule Delivery.

Oral administration is among the most convenient ways with good patient compliance for drug delivery; while it remains a challenge to achieve desirable bioavailability of most macromolecules due to the complex gastrointestinal barriers. Here, inspired by the structure and function of rocket, a novel micromotor delivery system is presented with scaled-down rocket-like architecture and effervescent-tablets-derived fuel for efficient oral macromolecule delivery by penetrating intestinal barrier. These rocket-inspired effervescent motors (RIEMs) are composed of sharp needle tips for both loading cargoes and efficient penetrating, and tail wings for loading effervescent powders and avoiding perforation. When exposed to a water environment, the effervescent fuel generates intensive CO2 bubbles to propel the RIEMs to move at high speed. Thus, the RIEMs with their sharp tip can inject into the surrounding mucosa for effective drug release. Furthermore, benefiting from their tail-wing design, perforation can be effectively avoided during the injection process, ensuring the safety of the RIEMs in gastrointestinal active delivery. Based on these advantages, it is demonstrated that the RIEMs can efficiently move and stab into the intestinal mucosa for insulin delivery, exhibiting efficacy in regulating blood sugar glucose in a diabetic rabbit model. These features indicate that these RIEMs are versatile and valuable for clinical oral delivery of macromolecules.

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.