Benthic bacterial communities indicate anthropogenic activity footprints in coastal area under long-term marine spatial planning practice

Marine spatial planning(MSP)is designed to divide the sea area into different types of functional zones,to implement corresponding development activities.However,the long-term impacts of anthropogenic activities associated with MSP practice on the marine microbial biosphere are still unclear.Yalu River Estuary,a coastal region in northeast of China,has been divided into fishery&agricultural(F&A)zone,shipping&port(S&P)zone and marine protected area(MPA)zone by a local MSP guideline that has been run for decades.To examine the effects of long-term executed MSP,benthic bacterial communities from different MSP zones were obtained and compared in this study.The results revealed significant differences in the bacterial community structure and predict functions among different zones.Bacterial genera enriched in different zones were identified,including SBR1031 in MPA,Woeseia and Sva0996 in S&P,and Halioglobus in F&A.In addition,correlations between some bacterial genera and sediment pollutants were uncovered.Furthermore,bacteria related to sulphide production were more abundant in the F&A zone,which was according to the accumulation of sulphides in this area.Moreover,bacteria associated with chemoheterotrophy and fermentation were more predominant in the S&P zone,consistent with high levels of organic matter and petroleum caused by shipping.Our findings indicated benthic bacterial communities could bring to light the anthropogenic activity footprints by different activities induced by long-term MSP practice.

Long-term nutrient variation trends and their potential impact on phytoplankton in the southern Yellow Sea,China

The concentration and composition of nutrients,such as N,P,and Si,respond to biogeochemical processes and in turn,impact the phytoplanktons'community structure and primary production.In this study,historical data was systematically analyzed to identify long-term variations in nutrient trends,red tide frequency,phytoplankton community abundance,and dominant species succession in the southern Yellow Sea(SYS).Results showed that N/P concentration ratios dramatically increased as a function of increasing dissolved inorganic nitrogen concentrations,and Si/N concentration ratios were generally larger than 1,indicating that N limitation morphed to P limitation and potentially to Si limitation,which impacted the phytoplankton community.Furthermore,inter-annual trends over the past 50 years show that phytoplankton community abundance has been higher in spring and summer,relative to autumn and winter.Moreover,with respect to red tide frequency,diatom abundance gradually decreased,while that of dinoflagellates gradually increased.Dominant species succession showed that the phytoplankton community exhibited an evident tendency to transform from diatoms to dinoflagellates.These research results clearly depict the presence of an important correlation between the phytoplankton community and nutrient structure in the SYS.

3D-printed tissue repair patch combining mechanical support and magnetism for controlled skeletal muscle regeneration

Physical forces,such as magnetic and mechanical stimulation,are known to play a significant role in the regulation of cell response.In the present study,a biomimetic regeneration patch was fabricated using E-jet 3 D printing,which integrates mechanical and magnetic stimulation in a biocompatible"one-pot reaction"strategy when combined with a static magnetic field(SMF).The magneto-based therapeutic regeneration patch induced myoblasts to form aligned and multinucleated myotubes,regulated the expression of myogenic-related genes,and activated the p38αmitogen-activated protein kinase pathway via the initiation of myogenic differentiation.To validate the efficiency of the proposed strategy,the regeneration patch was implanted into mice and exposed to a suitable SMF,which resulted in significantly enhanced in vivo skeletal muscle regeneration.The findings demonstrated that appropriate external physical stimulation provides a suitable biophysical microenvironment that is conducive to tissue regeneration.The method used in the present study represents a promising technique to induce the regeneration of damaged skeletal muscle tis sue.

Living Chinese Herbal Scaffolds from Microfluidic Bioprinting for Wound Healing

Biological scaffolds have been widely employed in wound healing applications,while their practical efficiency is compromised by insufficient oxygen delivery to the 3-dimensional constructs and inadequate nutrient supply for the long-term healing process.Here,we present an innovative living Chinese herbal scaffold to provide a sustainable oxygen and nutrient supply for promoting wound healing.Through a facile microfluidic bioprinting strategy,a traditional Chinese herbal medicine(Panax notoginseng saponins[PNS])and a living autotrophic microorganism(microalgae Chlorella pyrenoidosa[MA])were successfully encapsulated into the scaffolds.The encapsulated PNS could be gradually released from the scaffolds,which promoted cell adhesion,proliferation,migration,and tube formation in vitro.In addition,benefiting from the photosynthetic oxygenation of the alive MA,the obtained scaffolds would produce sustainable oxygen under light illumination,exerting a protective effect against hypoxia-induced cell death.Based on these features,we have demonstrated through in vivo experiments that these living Chinese herbal scaffolds could efficiently alleviate local hypoxia,enhance angiogenesis,and thereby accelerate wound closure in diabetic mice,indicating their great potential in wound healing and other tissue repair applications.

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.

Pt(Ⅳ) prodrug initiated microparticles from microfluidics for tumor chemo-, photothermal and photodynamic combination therapy

Multimodal treatment modalities hold great potential for cancer therapy,thus current efforts are focusing on the development of more effective and practical synergistic therapeutic platforms.Herein,we present a novel trans,trans,trans-[Pt(N_(3))_(2)(OH)_(2)(py)_(2)](Pt(Ⅳ))prodrug-initiated hydrogel microparticles(M_(ICG-Pt))with indocyanine green(ICG)encapsulation by microfluidics for efficiently synergistic chemo-,photothermal(PTT)and photodynamic therapy(PDT).The employed Pt(Ⅳ)could not only serves as an initiator to generate azidyl radical(N_(3)^(·))for photo-polymerization of methacrylate gelatin(GelMA)matrix,but also be reduced to high cytotoxic platinum(Ⅱ)(Pt(Ⅱ))species for tumor chemotherapy.The laden ICG with highly photothermal heating ability and intrinsic reactive oxygen species(ROS)productivity endows the M_(ICG-Pt) with effective PTT/PDT performances upon near-infrared(NIR)light irradiation.In addition,benefiting from the production of oxygen during the photo-activation process of Pt(Ⅳ),the PDT efficacy of ICG-laden M_(ICG-Pt) could be further enhanced.Based on these advantages,we have demonstrated that the M_(ICG-Pt) could significantly eliminate cancer cells in vitro,and remarkably suppressed the tumor growth in vivo via synergistic chemotherapy,PTT,and PDT.These results indicate that such Pt(Ⅳ)-initiated hydrogel microparticles are ideal candidates of multimodal treatment platforms,holding great prospects for cancer therapy.

Photopolymerized 3D Printing Scaffolds with Pt(IV) Prodrug Initiator for Postsurgical Tumor Treatment

Biomedical scaffolds have shown great success in postsurgical tumor treatment;their current efforts are focusing on eradicating residual tumor cells and circulating tumor cells and simultaneously repairing postoperative tissue defects.

In Situ 3D Bioprinting Living Photosynthetic Scaffolds for Autotrophic Wound Healing

Three-dimensional(3D)bioprinting has been extensively explored for tissue repair and regeneration,while the insufficient nutrient and oxygen availability in the printed constructs,as well as the lack of adaptive dimensions and shapes,compromises the overall therapeutic efficacy and limits their further application.Herein,inspired by the natural symbiotic relationship between salamanders and algae,we present novel living photosynthetic scaffolds by using an in situ microfluidic-assisted 3D bioprinting strategy for adapting irregular-shaped wounds and promoting their healing.As the oxygenic photosynthesis unicellular microalga(Chlorella pyrenoidosa)was incorporated during 3D printing,the generated scaffolds could produce sustainable oxygen under light illumination,which facilitated the cell proliferation,migration,and differentiation even in hypoxic conditions.Thus,when the living microalgae-laden scaffolds were directly printed into diabetic wounds,they could significantly accelerate the chronic wound closure by alleviating local hypoxia,increasing angiogenesis,and promoting extracellular matrix(ECM)synthesis.These results indicate that the in situ bioprinting of living photosynthetic microalgae offers an effective autotrophic biosystem for promoting wound healing,suggesting a promising therapeutic strategy for diverse tissue engineering applications.

Genetic approach to track neural cell fate decisions using human embryonic stem cells

With their capability to undergo unlimited self-renewal and to differentiate into all cell types in the body, human embryonic stem cells （hESCs） hold great promise in human cell therapy. However, there are limited tools for easily identifying and isolating live hESC-derived cells. To track hESC-derived neural progenitor cells （NPCs）, we applied homologous recombination to knock-in the mCherry gene into the Nestin locus of hESCs. This facilitated the genetic labeling of Nestin positive neural progenitor cells with mCherry. Our reporter system enables the visualization of neural induction from hESCs both in vitro （embryoid bodies） and in vivo （ter- atomas）. This system also permits the identification of different neural subpopulations based on the intensity of our fluorescent reporter. In this context, a high level of mCherry expression showed enrichment for neural progenitors, while lower mCherry corresponded with more committed neural states. Combination of mCherry high expression with cell surface antigen staining enabled further enrichment of hESC-derived NPCs. These mCherry＊ NPCs could be expanded in culture and their differentiation resulted in a down-regulation of mCherry consistent with the loss of Nestin expression. Therefore, we have developed a fluorescent reporter system that can be used to trace neural differentiation events of hESCs.

Shear-flow-induced graphene coating microfibers from microfluidic spinning

The advancements in flexible electronics call for invention of fiber-based electronic systems by surface modification or encapsulation.Here we present novel shear-flow-induced graphene nanosheets coating microfibers by integrating the dip coating approach with the microfluidic spinning method.The core hydrogel microfiber was first spun continuously from the microfluidic device,and the shear flow from the dip coating approach allowed formation of the thin graphene oxide(GO)nanosheet coating shell.

Microfluidic 3D printing polyhydroxyalkanoates-based bionic skin for wound healing

Biomimetic scaffolds with extracellular matrix(ECM)-mimicking structure have been widely investigated in wound healing applications,while insufficient mechanical strength and limited biological activity remain major challenges.Here,we present a microfluidic 3D printing biomimetic polyhydroxyalkanoates-based scaffold with excellent mechanical properties and hierarchical porous structures for enhanced wound healing.This scaffold is composed of poly(3-hydroxybutyrate-4-hydroxybutyrate)and polycaprolactone,endowing it with excellent tensile strength(2.99 MPa)and degradability(80%of weight loss within 7 d).The ECM-mimicking hierarchical porous structure allows bone marrow mesenchymal stem cells(BMSCs)and human umbilical vein endothelial cells(HUVECs)to proliferate and adhere on the scaffolds.Besides,anisotropic composite scaffolds loaded with BMSCs and HUVECs can significantly promote re-epithelization,collagen deposition and capillary formation in rat wound defects,indicating their satisfactory in vivo tissue regenerative activity.These results indicate the feasibility of polyhydroxyalkanoates-based biomimetic scaffolds for skin repair and regeneration,which also provide a promising therapeutic strategy in diverse tissue engineering applications.

Emerging biomaterials for reproductive medicine

Reproduction is the most important event for the continuation of life.Unfortunately,infertility is a widespread problem.Recently,biomaterials have been widely used in reproductive biology,including tissue engineering,regenerative medicine and contraception.In this review,we summarize the research progress of biomaterials applied in follicle culture,artificial ovary,tissue engineering,and contraception.We first introduce the applications and advantages of different biomaterials in follicle culture and artificial ovary.Then,we summarize the biomaterials for tissue engineering in reproductive biology.Also,we introduce the applications of biomaterials for contraception.Besides,some emerging technologies are also introduced,such as microfluidic chip,organ chip,3D printing,electrostatic spinning and stem cell therapy in the fundamental research and clinical application.We believe that this review will promote the interdisciplinary communication between biomaterial science and reproductive biology.

Ellipsoidal porous patch with anisotropic cell inducing ability for inhibiting skin scar formation

Scar formation has always been a difficult point to overcome in the field of clinical wound care.Here,we present an ellipsoidal porous patch with cell inducing ability for inhibiting scar formation.The patch was prepared by stretching a poly(lactic-co-glycolic acid)(PLGA)inverse opal film at the glass transition temperature to form a neatly arranged three-dimensional ellipsoidal porous structure.Such anisotropic structure showed dramatic capability in directing cell growth and arrangement by reconstructing cell morphology.Besides,the prolifera-tion of cells growing on the stretched patch was significantly suppressed without cell cytotoxicity.In addition,benefitting from the abundant and connected nanopores,the patch could be imparted with a potent ability to promote cell migration by encapsulating fibroblast growth factor 2(FGF2)via the second filling of functional gelatin methacryloyl(GelMA)hydrogel into its scaffold.In a typical scar model,we have demonstrated that the resultant patch performed well in inhibiting scar formation characterized by inhibiting the excessive proliferation of fibroblasts,decreasing the deposition of type I collagen,reducing the scar index and achieved complete tissue reconstruction.These results indicate the anisotropic inverse opal patch has an excellent application prospect in inhibiting scar formation during wound repair.

Biomimetic epithelium/endothelium on chips

Epithelium and endothelium,occupying a significant proportion of cells in the human body,play a crucial role in maintaining organs’normal structure and function.Various methods have been employed to study the physiology and pathology of epithelium and endothelium.However,these conventional methods,such as animal trials and two-dimensional(2D)cell culture,fail to precisely simulate the complex biology of the human body due to the species difference and lack of the native microenvironment in human systems,which is essential for cell culture.To overcome these limitations,epithelium/endothelium on chips have been proposed,which can mimic the pathophysiology of native human systems in a controllable way.This review introduces the recent progress in epithelium/endothelium on chips,aiming to provide a comprehensive review of the fabrication and application of this technology.We first depict the chips’basic components,materials,and fabrication techniques.Then,we focus on different chip types,from single cell-on-chip,single organ/tissue-on-chip,to multi-organs-on-chip.After that,we describe the biomedical applications such as in vitro study of the physiology and interaction of organs,construction of disease models,and drug development.Finally,the recent challenges and future outlook of epithelium/endothelium on chips are discussed.

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.