Microfluidics for Medical Additive Manufacturing

Additive manufacturing plays a vital role in the food,mechanical,pharmaceutical,and medical fields.Within these fields,medical additive manufacturing has led to especially obvious improvements in medical instruments,prostheses,implants,and so forth,based on the advantages of cost-effectiveness,customizability,and quick manufacturing.With the features of precise structural control,high throughput,and good component manipulation,microfluidic techniques present distinctive benefits in medical additive manufacturing and have been applied in the areas of drug discovery,tissue engineering,and organs on chips.Thus,a comprehensive review of microfluidic techniques for medical additive manufacturing is useful for scientists with various backgrounds.Herein,we review recent progress in the development of microfluidic techniques for medical additive manufacturing.We evaluate the distinctive benefits associated with microfluidic technologies for medical additive manufacturing with respect to the fabrication of droplet/fiber templates with different structures.Extensive applications of microfluidic techniques for medical additive manufacturing are emphasized,such as cell guidance,three-dimensional(3D)cell culture,tissue assembly,and cell-based therapy.Finally,we present challenges in and future perspectives on the development of microfluidics for medical additive manufacturing.

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.

DSEMR: A database for special environment microorganisms resource and associating them with synthetic biological parts

Special environmental microorganisms are considered to be of great industrial application value because of their special genotypes,physiological functions and metabolites.The research and development of special environmental microorganisms will certainly bring about some innovations in biotechnology processes and change the face of bioengineering.The Special Environmental Microbial Database(DSEMR)is a comprehensive database that provides information on special environmental microbial resources and correlates them with synthetic biological parts.DSEMR aggregates information on specific environmental microbial genomes,physiological properties,culture media,biological parts,and metabolic pathways,and provides online tool analysis data,including 5268 strains from 620 genera,31 media,and 42,126 biological parts.In short,DSEMR will become an important resource for the study of microorganisms in special environments and actively promote the development of synthetic biology.

Blockade of Arf1-mediated lipid metabolism in cancers promotes tumor infiltration of cytotoxic T cells via the LPE-PPARγ-NF-κB-CCL5 pathway

Tumor immunotherapy has achieved breakthroughs in a variety of tumors. However, the systemic absence of T cells in tumors and immunosuppressive tumor microenvironment so far limits the efficacy of immunotherapy to a small population of patients. Therefore, novel agents to increase T-cell tumor infiltration are urgently needed in the clinic. We recently found that inhibition of the ADP-ribosylation factor 1 (Arf1)-mediated lipid metabolism not only kills cancer stem cells (CSCs) but also elicits an anti-tumor immune response. In this study, we revealed a mechanism that targeting Arf1 promotes the infiltration of cytotoxic T lymphocytes (CTLs) into tumors through the C-C chemokine ligand 5 (CCL5)- C-C chemokine receptor type 5 (CCR5) pathway. We found that blockage of Arf1 induces the production of the unsaturated fatty acid (PE 18:1) that binds and sequestrates peroxisome proliferator- activated receptor-γ (PPARγ) from the PPARγ-nuclear factor-κB (NF-κB) cytoplasmic complex. The released NF-κB was then phospho-rylated and translocated into the nucleus to regulate the transcription of chemokine CCL5. CCL5 promoted infiltration of CTLs for tumor regression. Furthermore, the combination of the Arf1 inhibitor and programmed cell death protein 1 (PD-1) blockade induced an even stronger anti-tumor immunity. Therefore, targeting Arf1 represents a novel anti-tumor immune approach by provoking T-cell tumor infiltration and may provide a new strategy for tumor immunotherapy.

MXene-Integrated Microneedle Patches with Innate Molecule Encapsulation for Wound Healing

Wound healing is a complex physiological process that involves coordinated phases such as inflammation and neovascularization.Attempts to promote the healing process tend to construct an effective delivery system based on different drugs and materials.In this paper,we propose novel MXene-integrated microneedle patches with adenosine encapsulation for wound healing.Owing to the dynamic covalent bonding capacity of boronate molecules with adenosine,3-(acrylamido)phenylboronic acid-(PBA-)integrated polyethylene glycol diacrylate(PEGDA)hydrogel is utilized as the host material of microneedle patches.Benefitting from photothermal conversion capacity of MXene,the release of loaded adenosine could be accelerated under NIR irradiation for maintaining the activation signal around injury site.In vitro cell experiments proved the effect of MXene-integrated microneedle patches with adenosine encapsulation in enhancing angiogenesis.When applied for treating animal models,it is demonstrated that the microneedle patches efficiently promote angiogenesis,which is conductive to wound healing.These features make the proposed microneedle patch potential for finding applications in wound healing and other biomedical fields.

Smart Microneedles for Therapy and Diagnosis

Microneedles represent a cutting-edge and idea-inspiring technology in biomedical engineering,which have attracted increasing attention of scientific researchers and medical staffs.Over the past decades,numerous great achievements have been made.The fabrication process of microneedles has been simplified and becomes more precise,easy-to-operate,and reusable.Besides,microneedles with various features have been developed and the microneedle materials have greatly expanded.In recent years,efforts have been focused on generating smart microneedles by endowing them with intriguing functions such as adhesion ability,responsiveness,and controllable drug release.Such improvements enable the microneedles to take an important step in practical applications including household drug delivery devices,wearable biosensors,biomedical assays,cell culture,and microfluidic chip analysis.In this review,the fabrication strategies,distinctive properties,and typical applications of the smart microneedles are discussed.Recent accomplishments,remaining challenges,and future prospects are also presented.

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.

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.

Bioinspired structural color particles with multi-layer graphene oxide encapsulated nanoparticle components

Because of the unique features of spherical symmetry,angle-independency,good monodispersity,controllable components and morphologies,structural color particles(SCPs)have found great significances in various fields such as sensing,monitoring,biological assays,etc.Here,inspired by the melanosome-derived bright structural colors and the self-adhesivity of mussels,we present a kind of bioinspired SCPs assembled from polydopamine(PDA)-adhered multi-layer graphene oxide(GO)encapsulated silica nanoparticles(SNs).It is demonstrated that compared with traditional SCPs,the designed particles possess brighter and more vibrant structural colors,and no complicated modification is required during the functionalization process due to the abundant inherent functional groups of GO.The resultant SCPs are verified to be capable for direct hybridization chain reaction and multiplexed nucleic acid assays.These properties indicate the promising prospects of our designed SCPs.

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.

Alkaloid Dimers Isolated from Thalictrum baicalense Have Antitumor Activities

Comprehensive Summary A pair of heterodimeric isoquinoline alkaloid enantiomers,(+)thaliberberine A,five new thalifaberine-type aporphine-benzylisoquinoline(ABl)alkaloids,thalicultratines M-Q,and thirteen known analogues were isolated from the roots of Thalictrum baicalense Turcz.ex Ledeb.The structures were determined by extensive spectroscopic methods and ECD calculations.Thaliberberine A featuring a novel carbon skeleton coupled by two different classes of isoquinoline alkaloids,protoberberine and phthalidoisoquinoline,represents the first natural product with the berberine skeleton substituted at C-6.Plausible biosynthetic routes of 1 are proposed.