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.

Microfluidic Generation of Multicomponent Soft Biomaterials

Soft biomaterials hold great potential for a plethora of biomedical applications because of their deforma-bility,biodegradability,biocompatibility,high bioactivity,and low antigenicity.Multicomponent soft bio-materials are particularly attractive as a way of accommodating components made of different materials and generating combinative functions.Microfluidic technology has emerged as an outstanding tool in generating multicomponent materials with elaborate structures and constituents,in that it can manipu-late multiphasic flows precisely on the micron scale.In recent decades,much progress has been achieved in the microfluidic fabrication of multicomponent soft biomaterials with finely defined physicochemical properties capable of controllable therapeutics delivery,three-dimensional(3D)cell culture,flexible devices and wearable electronics,and biosensing for molecules.In the paper,we summarize current pro-gress in multicomponent soft biomaterials derived from microfluidics and emphasize their applications in biomedical fields.We also provide an outlook of the remaining challenges and future trends in this field.

Functional PEGylated bacteria reinforce the intestinal mucosal barrier by effective mucus-penetration

Recently,the intestinal mucosal barrier has attracted considerable attention from the scientific community.With the in-depth exploration of this barrier,it has become increasingly clear that the mucosal barrier is a complicated system consisting of multiple components.In general,the intestinal mucosal barrier mainly consists of intestinal epithelial cells covered with a highly viscous gellike layer containing symbiotic microorganisms and rich antimicrobial agents that can effectively protect the human body from the invasion of harmful microorganisms and toxins.

Bio-inspired dual-adhesive particles from microfluidic electrospray for bone regeneration

Bioadhesive hydrogels have demonstrated great potential in bone regeneration.However,the relatively simple adhesion mechanism and lack of intricate structural design restrict their further applications.Herein,inspired by multiple adhesion mechanisms of pollen particles and marine mussels,we present a novel type of dual-adhesive hydrogel particles fabricated from microfluidic electrospray for bone regeneration.As the particles are rapidly solidified via liquid nitrogen-assisted cryogelation,they exhibit pollen-mimicking hierarchical porous morphology and gain structure-related adhesion.Besides,the particles are further coated by polydopamine(PDA)to achieve molecular-level adhesion especially to physiological wet surfaces of bone issues.Benefiting from such dual-adhesion mechanisms,the particles can strongly adhere to bone tissue defects,and function as porous scaffolds.Moreover,the dual-adhesive particles can serve as effective vehicles to release key growth factors more than two weeks.In vitro experiments showed that the growth factors-loaden particles have excellent biocompatibility and more significantly promote angiogenesis(~2-fold)and osteogenic differentiation(~3-fold)than control.In vivo experiments indicated that the dual-adhesive particles could significantly enhance bone regeneration(~4-fold)than control by coupling osteogenesis and angiogenesis effects.Based on these features,the bio-inspired dual-adhesive particles have great potentials for bone repair and wound healing applications.

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.

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 fabricatejellyfish-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 stimuliresponsive 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 piezoelectricintegrated microfluidic strategy could open an avenue for the creation of such anisotropic particles.

DNA-Polyelectrolyte Composite Responsive Microparticles for Versatile Chemotherapeutics Cleaning

Drug therapy is among the most widely used methods in disease treatment.However,there remains a trade-off problem between drug dosage and toxicity.Blood purification by adsorption of excessive drugs during clinical treatment could be a solution for enhancing therapeutic efficacy while maintaining normal body function.Here,inspired by the intrinsic action mechanism of chemotherapeutic agents in targeting DNA in the cell nucleus,we present DNA-polyelectrolyte composite responsive microparticles for chemotherapeutics cleaning.The presence of DNA in the microparticles enabled the adsorption of multiple common chemotherapy drugs.Moreover,the microparticles are endowed with a porous structure and a photothermal-responsive ability,both of which contribute to improved adsorption by enhancing the contact of the microparticles with the drug solution.On the basis of that,the microparticles are integrated into a herringbone-structured microfluidic chip.The fluid mixing capacity and the enhanced drug cleaning efficiency of the microfluidic platform are validated on-chip.These results indicate the value of the DNA-polyelectrolyte composite responsive microparticles for drug capture and blood purification.We believe the microparticle-integrated microfluidic platform could provide a solution for settling the dosage-toxicity trade-off problems in chemotherapy.

Pollen-Inspired Photonic Barcodes with Prickly Surface for Multiplex Exosome Capturing and Screening

Exosomes,which play an important role in intercellular communication,are closely related to the pathogenesis of disease.However,their effective capture and multiplex screening are still challenging.Here,inspired by the unique structure of pollens,we present novel photonic crystal(PhC)barcodes with prickly surface by hydrothermal synthesis for multiplex exosome capturing and screening.These pollen-inspired PhC barcodes are imparted with extremely high specific surface area and excellent prickly surface nanostructures,which can improve the capture rate and detection sensitivity of exosomes.As the internal periodic structures are kept during the hydrothermal synthesis process,the pollen-inspired PhC barcodes exhibit obvious and stable structural colors for identification,which enables multiplex detection of exosomes.Thus,the pollen-inspired PhC barcodes can not only effectively capture and enrich cancer-related exosomes but also support multiplex screening of exosomes with high sensitivity.These features make the prickly PhC barcodes ideal for the analysis of exosomes in medical diagnosis.

Bio-inspired clamping microneedle arrays from flexible ferrofluid-configured moldings

Microneedle(MN)arrays have demonstrated value for cosmetics,diagnosis,transdermal drug delivery,and other biomedical areas.Much effort has been devoted to developing simple stratagem for creating versatile moldings and generating functional MN arrays.Here,inspired by the serrated microstructure of mantises’forelegs,we present a novel serration-like clamping MN array based on ferrofluidconfigured moldings.Benefiting from the flexibility and versatility of ferrofluids,negative microhole array moldings with various sizes and angles toward the midline could be created easily.The corresponding biocompatible polymer MN arrays with both isotropic and anisotropic structures could then be produced feasibly and cost-effectively by simply replicating these moldings.It was found that the resultant serrated clamping MN arrays had the ability to adhere to skin firmly,enabling them to be used over a relatively long time and while the recipient was moving.This proposed technology performed well in minimally invasive drug administration and sustained glucocorticoids release during treatment for imiquimod-induced psoriasis in mice.These features indicated that such MN arrays could play important roles in wearable transdermal drug delivery systems and in other applications.

Chinese herb microneedle patch for wound healing

Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement.Attempts in this area tend to develop new forms to make their applications more convenient and wider.Here,we propose a novel Chinese herb microneedle(CHMN)patch by integrating the herbal extracts,Premna microphylla and Centella asiatica,with microstructure of microneedle for wound healing.Such path is composed of sap extracted from the herbal leaves via traditional kneading method and solidified by plant ash derived from the brine induced process of tofu in a well-designed mold.Because the leaves of the Premna microphylla are rich in pectin and various amino acids,the CHMN could be imparted with medicinal efficacy of heat clearing,detoxicating,detumescence and hemostatic.Besides,with the excellent pharmaceutical activity of Asiatic acid extracted from Centella asiatica,the CHMN is potential in promoting relevant growth factor genes expression in fibroblasts and showing excellent performance in anti-oxidant,anti-inflammatory and anti-bacterial activity.Taking advantages of these pure herbal compositions,we have demonstrated that the derived CHMN was with dramatical achievement in anti-bacteria,inhibiting inflammatory,collagen deposition,angiogenesis and tissue reconstruction during the wound closure.These results indicate that the integration of traditional Chinese herbs with progressive technologies will facilitate the development and promotion of traditional Chinese medicine in modern society.

Thriving microfluidic technology

Microfluidics refers to the technology that processes a small volume of fluids and exploits their specific properties at the sub-microliter scale in microchannels.When the fluid dimensions scale down to the microscale level,the specific surface area of the fluids increases,thus exhibiting behaviors divergent from those of the bulk fluids.Compared with the bulk systems,microfluidics technology offers many salient advantages.

Responsive Janus Structural Color Hydrogel Micromotors for Label-Free Multiplex Assays

Micromotors with self-propelling ability demonstrate great values in highly sensitive analysis.Developing novel micromotors to achieve label-free multiplex assay is particularly intriguing in terms of detection efficiency.Herein,structural color micromotors(SCMs)were developed and employed for this purpose.The SCMs were derived from phase separation of droplet templates and exhibited a Janus structure with two distinct sections,including one with structural colors and the other providing catalytic selfpropelling functions.Besides,the SCMs were functionalized with ion-responsive aptamers,through which the interaction between the ions and aptamers resulted in the shift of the intrinsic color of the SCMs.It was demonstrated that the SCMs could realize multiplex label-free detection of ions based on their optical coding capacity and responsive behaviors.Moreover,the detection sensitivity was greatly improved benefiting from the autonomous motion of the SCMs which enhanced the ion-aptamer interactions.We anticipate that the SCMs can significantly promote the development of multiplex assay and biomedical fields.

Pollens derived magnetic porous particles for adsorption of low-density lipoprotein from plasma

Adsorption of low-density lipoprotein from plasma is vital for the treatment of dyslipidemia.Appropriate adsorbent material for efficient and selective adsorption of low-density lipoprotein is highly desired.In this work,we developed pollens-derived magnetic porous particles as adsorbents for this purpose.The natural pollen grains were modified to obtain high surface porosity,a large inner cavity,magnet responsiveness,and specific wettability.The resultant particles exhibited satisfying performance in the adsorption of a series of oils and organic solvents out of water.Besides,the particles were directly utilized to the adsorption of low-density lipoprotein in plasma,which showed high selectivity,and achieved an outstanding adsorption capacity as high as 34.9%within 2 h.Moreover,their salient biocompatibility was demonstrated through simulative hemoperfusion experiments.These features,together with its abundant source and facile fabrication,makes the pollens-derived magnetic porous particles excellent candidate for low-density lipoprotein-apheresis and water treatment applications.

Tiny water droplet with huge power

Water occupies 70% of the earth’s surface.It not only supports our life but also contains abundant energy.Water exists in different forms,including in oceans,rivers,and lakes,where they can evaporate upon solar radiation.The temperature difference in the atmosphere acts like a pump to pull up the evaporated water,through which the water in the cloud obtains the gravitational potential energy.Such energy then transfers into kinetic energy in the raindrops falling down[1].How to utilize the raindrops’energy has long been a fascinating question.Although traditional hydraulic power generation is more applicable to continuous flow of water,it becomes inefficient with relatively less rainfall supply[2].Therefore,a new strategy to harvest the kinetic energy stored in the form of raindrops is highly desired.

Boston Ivy-Inspired Disc-Like Adhesive Microparticles for Drug Delivery

Microparticles with strong adherence are expected as efficient drug delivery vehicles.Herein,we presented an ingenious hydrogel microparticle recapitulating the adhesion mechanism of Boston ivy tendrils adhesive discs(AD)for durable drug delivery.The particles were achieved by replicating a silica colloidal crystal aggregates assembled in a droplet template after rapid solvent extraction.Due to their unique shape,the nanostructure,and the sticky hydrogel component,such novel microparticles exhibited prominent adhesive property to the wet tissue environment.It was demonstrated that the bioinspired microcarriers loading with dexamethasone had a good therapeutic effect for ulcerative colitis due to the strong adhesion ability for prolonging the maintenance of drug availability.These virtues make the biomimetic microparticles potentially ideal for many practical clinical applications,such as drug delivery,bioimaging,and biodiagnostics.

Living Materials for Regenerative Medicine

Regenerative medicine has been attracting tremendous attention during the past few decades because it is promising in overcoming the limitations of donor shortage and immune complications in direct transplantations.The ongoing progress in this field calls for the rapid growth of living materials,which consist of live biological agents and can be designed together with synthetic materials to meet the application demands of regenerative medicine.In this review,we present a summary of the state-of-the-art progress of living materials that are applied in regenerative medicine.We first introduce the advanced engineering approaches that are employed to prepare living materials containing live cells,typically including genetic engineering,cell coating,microfluidics,and bioprinting,etc.Afterwards,we enumerate different application aspects of living materials in regenerative medicine,including tissue scaffold,cell therapy,tissue models,and so on.Finally,we give a concise conclusion and provide a perspective of this field.

Biomimic organ architectures and functions by assembling organoid models

An artificial organ is a synthetic device implanted into the living body as a substitute for a diseased organ.It is a long-term dream toward prolonging life by restoring or augmenting the functions of actual organs.The artificial organ has been attracting increasing attention in a variety of fields,such as tissue engineering,drug discovery,precision medicine,etc.[1].

Cellular fluidic-based vascular networks for tissue engineering

Artificial organs are devices implanted into the living body as a substitute for damaged or diseased organs.Current efforts focus on the construction of fully functionalized artificial tissues/organs with vascular networks.Although engineering efforts have been made in creating artificial vessels with simple or complex configurations,building vascular networks with hierarchical architectures approximating native counterparts remains challenging.Herein,we give a perspective of cellular fluidics-based construction of vascular networks for tissue engineering,with inspirations drawn from a novel concept of 3D fluidic control platform based on unit-cell constructs.Through architected design of the unit cells,it enables programmed control over gas-liquid-solid interfaces and fluid flow processes in open-cell structures.This cellular-fluidics concept and the associated platform provide lots of inspirations for constructing artificial vascular networks.We believe that cellular fluidics opens a new avenue for fluid control and deterministic delivery,and would find vast opportunities in tissue engineering.

Programmable microfluidic manipulations for biomedical applications

Fluid manipulation plays an important role in biomedical applications such as biochemical assays,medical diag-nostics,and drug development.Programmable fluidic manipulation at the microscale is highly desired in both fundamental and practical aspects.In this paper,we summarize some of the latest studies that achieve pro-grammable fluidic manipulation through intricate capillaric circuits design,construction of biomimetic metasur-face,and responsive surface wettability control.We highlight the working principle of each system and concisely discuss their design criterion,technical improvements,and implications for future study.We envision that with multidisciplinary efforts,microfluidics would continue to bring vast opportunities to biomedical fields and make contributions to human health.

Microfluidic single-cell coating with defined chemomechanical cues for cell therapy

Cell surface coating is an emerging technology that represents one of the most popular methods for cell engineering. Cell engineering refers to a series of techniques used to enhance or augment cell functions through either genetic alteration or physical/chemical modifications [1,2]. In the past few years, a lot of cell engineering strategies have been developed, and the engineered cells have been widely applied in drug delivery, cell therapy, tissue regeneration [3–5], etc. However, most of the engineering methods are based on a bulk system whereby cells are modified collectively.This poses challenges in studying the cell functions due to limited control of the microenvironment. For example, microgel carriers encapsulating cells with high cell densities results in limited substance transport between cells and the microenvironment. Besides,the impact of many chemical modifications on cellular functions and behaviors remains unclear. By contrast, single cell level engineering strategies provide sufficient substance transport and a more controllable physical and chemical microenvironment than bulk systems [6,7]. Therefore, a facile engineering approach for deterministic single-cell microenvironment control is highly desired.