摘要：Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural *** in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted *** oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain *** study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with *** report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide ***,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase *** study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release ***,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal *** showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new *** findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated *** work thereby offers a promising avenue for the development of functional tissues with e

摘要：The immune response after implantation of a biomaterial may shorten the functional life of the implant,depending on the degree of the *** this study,we used a polyacrylamide-alginate(PAAm-Alg)hydrogel,which has been previously characterized as a biocompatible material and shown to enhance regeneration of cartilage in vivo,along with a graphiteenhanced hydrogel(PAAm-Alg-G)as a non-biocompatible counterpart,to evaluate macrophage attachment and polarization to pro-or anti-inflammatory *** performance of each biomaterial in the presence of fibroblasts and chondrocytes was validated by an in vitro model which demonstrated modulation of the foreign-body response.A blend of 5%gelatin methacryloyl and 0.1%methacrylated hyaluronic acid was optimized to mimic the extracellular matrix(ECM)and support cell viability,proliferation,migration,and functionality at an initial concentration of 3.25×10^(5) cells/*** PAAm-Alg-G hydrogel localized in the simulated ECM showed cytotoxic and genotoxic effects for both fibroblasts and chondrocytes,while exhibiting a proliferative effect on macrophages with elevated immune *** M1/M2 ratio was 0.73 for PAAm-Alg hydrogel but 2.64 for PAAm-Alg-G,leading to significant M1 dominance(p0.05).The interleukin-6(IL-6)concentration secreted in the presence of PAAm-Alg hydrogel(4.58 pg/mL)significantly decreased(p<0.0001)on day 13,while the increase(p<0.0001)in interleukin-10(IL-10)concentration(120.73 pg/mL)confirmed the switch from a pro-inflammatory to an anti-inflammatory *** immune responses by developing a simplistic yet powerful three-dimensional in vitro model provides advantages in preparing for clinical use of biomaterials.

摘要：Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory ***,the development of a model for effective drug screening is urgently *** the established therapeutic testing models for CCA are often ineffective,we fabricated an enabling three-dimensional(3D)-bioprinted CCA-on-a-chip model that to a good extent resembled the multicellular microenvironment and the anatomical microstructure of the hepato-vascular-biliary system to perform high-content antitumor drug ***,cholangiocytes,hepatocytes,and vascular endotheliocytes were employed for 3D bioprinting of the models,allowing for a high degree of spatial and tube-like microstructural ***,it was possible to observe CCA cells attached to the surfaces of the gelatin methacryloyl(GelMA)hydrogelembedded microchannels and overgrown in a thickening manner,generating bile duct stenosis,which was expected to be analogous to the in vivo *** 4000 differentially expressed genes were detected in the CCA cells in our 3D coculture model compared to the traditional two-dimensional(2D)*** screening revealed that the CCA cells grown in the 3D traditional model were more sensitive to the antitumoral prodrug than those in the 2D monoculture due to drug biotransformation by the neighboring functional *** study provides proof-of-concept validation of our bioprinted CCA-on-a-chip as a promising drug screening model for CCA treatment and paves the way for potential personalized medicine strategies for CCA patients in the future.

摘要：We report the development of a metastasis-on-a-chip platform to model and track hepatocellular carcinoma(HCC)-bone metastasis and to analyze the inhibitory effect of an herb-based compound,thymoquinone(TQ),in hindering the migration of liver cancer cells into the bone *** bioreactor consisted of two chambers,one accommodating encapsulated HepG2 cells and one bone-mimetic niche containing hydroxyapatite(HAp).Above these chambers,amicroporous membrane was placed to resemble the vascular barrier,where medium was circulated over the *** was observed that the liver cancer cells proliferated inside the tumor microtissue and disseminated from the HCC chamber to the circulatory flow and eventually entered the bone *** number of metastatic HepG2 cells to the bone compartment was remarkably higher in the presence of HAp in the *** was then used as ametastasis-controlling agent in both free form and encapsulated nanoparticles,to analyze its suppressing effect on HCC *** indicated that the nanoparticle-encapsulated TQ provided a longer period of inhibitory *** summary,HCC-bone metastasis-on-a-chip platform was demonstrated to model certain key aspects of the cancer metastasis process,hence corroborating the potential of enabling investigations on metastasis-associated biology as well as improved anti-metastatic drug screening.

摘要：Reproducibility of clinical output is important when investigating therapeutic efficacy in pre-clinical animal *** to its physiological relevance,a swine myocardial infarction(MI)model has been widely used to evaluate the effectiveness of stem cells or tissue-engineered constructs for ischemic heart *** methods are used to induce MI in the swine ***,it is difficult,using these approaches,to obtain a similar level of functional outcomes from a group of animals due to interpersonal variation,leading to increased experimental ***,in order to minimize human intervention,we developed an approach to use a customized occluder that has dimensional similarities with that of the coronary artery of animals in the case of the swine *** carried out angiography to measure the diameter of the middle left anterior descending artery of each individual animal to fabricate the customized occluder using a 3D-printing *** fabricated occluder contained a central hole smaller than that of the targeted middle left anterior descending artery to mimic an atherosclerotic coronary artery that has an approximately 20%blocked ***,the 3D-printed occluder can provide continuous blood flow through the central pore,indicating a high survival rate(88%)of up to 28 days *** method showed the possibility of creating consistent myocardial infarction induction as compared to the conventional representative closed-chest method(50%survival rate),thus highlighting how our method can have a profound effect on accelerating reliable experiments for developing new therapeutic approaches to ischemic heart diseases.

摘要：Plant extracts are widely studied for their anti-cancer and cancer preventive effects. In this study, we compared the leukemia growth inhibition effects of seven different plant extracts, theaflavin, epigallocatechin gallate (EGCG), epicathechin (EC), apigenin, quercetin, chrysin and tannic acid, in vitro using the K562 erythroleukemia cell line and application of the design of experiments (DoE) methodology. Our systematic approach enabled us to isolate the main factor contribution, two-factor interactions and produced interaction relationships and/or models to describe growth inhibitory effects of different plant extracts when they are used in combination. The results identified tannic acid as the most significant inhibitor in this group and had synergistic effects with EGCG at specific concentrations. The fitted model of their combined effects showed that the most potent combination is at low concentrations of tannic acid (10 - 20 μM) and high concentrations of EGCG (80 - 100 μM). We further showed that tannic acid induced both growth inhibition and apoptosis in K562 cells in ranges between 10 - 100 μM. The polyphenol caused cell cycle arrest at G2- phase under the higher concentrations. In summary, use of DoE techniques effectively identified the most prominent inducer in this group of plant bioactive compounds and produced combinatorial bioactivity of various polyphenols and flavonoids over the entire range of concentrations under study. This study exemplifies the usefulness of DoE and serves as a guide in its utility for in vitro assessment of bioactivity in plant constituents.

摘要：Brain tumors’severity ranges from benign to highly aggressive and *** tools can assist in understanding the pathophysiology of these tumors from outside the body and facilitate development of suitable antitumoral ***,we first describe the physiology and cellular composition of brain ***,we discuss the development of threedimensional tissue models utilizing brain tumor *** particular,we highlight the role of hydrogels in providing a biomimetic support for the cells to grow into defined *** technologies,such as electrospinning and bioprinting,and advanced cellular models aim to mimic the extracellular matrix and natural cellular localization in engineered tumor ***,we review current applications and prospects of hydrogels for therapeutic purposes,such as drug delivery and co-administration with other *** further development,hydrogels can serve as a reliable option for in vitro modeling and treatment of brain tumors for translational medicine.

摘要：The long atmospheric residence time of CO2 creates an urgent need to add atmospheric carbon drawdown to CO2 regulatory *** and systems biology(SSB),which enables manipulation of cellular phenotypes,offers a powerful approach to amplifying and adding new possibilities to current land management practices aimed at reducing atmospheric *** participants(in attendance:Christina Agapakis,George Annas,Adam Arkin,George Church,Robert Cook-Deegan,Charles DeLisi,Dan Drell,Sheldon Glashow,Steve Hamburg,Henry Jacoby,Henry Kelly,Mark Kon,Todd Kuiken,Mary Lidstrom,Mike MacCracken,June Medford,Jerry Melillo,Ron Milo,Pilar Ossorio,Ari Patrinos,Keith Paustian,Kristala Jones Prather,Kent Redford,David Resnik,John Reilly,Richard ***,Daniel Segre,Susan Solomon,Elizabeth Strychalski,Chris Voigt,Dominic Woolf,Stan Wullschleger,and Xiaohan Yang)identified a range of possibilities by which SSB might help reduce greenhouse gas concentrations and which might also contribute to environmental sustainability and *** include,among other possibilities,engineering plants to convert CO2 produced by respiration into a stable carbonate,designing plants with an increased root-to-shoot ratio,and creating plants with the ability to self-fertilize.A number of serious ecological and societal challenges must,however,be confronted and resolved before any such application can be fully assessed,realized,and deployed.

摘要：Over the course of civilization,humans have increasingly expanded their freedom to live a better *** comparison with the primitive society,our modern society has many more choices of life-supporting resources,such as yearround food supply,permanent shelters,diverse energy sources,and effective preventive and curing ***,our society is currently still heavily relying on the resources provided by Mother Nature,which cannot meet the future global needs in terms of both quantity and quality under the pressure of population growth,natural resource reduction,and environmental *** example,the food sources originating from plants,animals,or microbes do not have the nutrition balance for optimal human health[1–3].Climate change and environmental deterioration threaten the food security[4–6].Increasingly,infectious diseases(e.g.,HIV/AIDS),genetic diseases(e.g.,cancer),and improper lifestyle-related disorders(e.g.,obesity)become more prevalent and remain challenging to be prevented,controlled,and *** medical technologies and modern medicine development are also meeting the ceiling.