Biomanufacturing,which uses renewable resources as raw materials and uses biological processes to produce energy and chemicals,has long been regarded as a production model that replaces the unsustainable fossil econom...Biomanufacturing,which uses renewable resources as raw materials and uses biological processes to produce energy and chemicals,has long been regarded as a production model that replaces the unsustainable fossil economy.The construction of non-natural and efficient biosynthesis routes of chemicals is an important goal of green biomanufacturing.Traditional methods that rely on experience are difficult to support the realization of this goal.However,with the rapid development of information technology,the intelligence of biomanufacturing has brought hope to achieve this goal.Retrobiosynthesis and computational enzyme design,as two of the main technologies in intelligent biomanufacturing,have developed rapidly in recent years and have made great achievements and some representative works have demonstrated the great value that the integration of the two fields may bring.To achieve the final integration of the two fields,it is necessary to examine the information,methods and tools from a bird’s-eye view,and to find a feasible idea and solution for establishing a connection point.For this purpose,this article briefly reviewed the main ideas,methods and tools of the two fields,and put forward views on how to achieve the integration of the two fields.展开更多
Biomanufacturing(BM)is a multidisciplinary area incorporating the characteristics of living organisms and engineering principles to create valuable products for various sectors,including medicine,energy,and the enviro...Biomanufacturing(BM)is a multidisciplinary area incorporating the characteristics of living organisms and engineering principles to create valuable products for various sectors,including medicine,energy,and the environment.BM has undergone a remarkable transformation in the last two decades,entering the era of BM4.0 and becoming a pivotal driver of the sustainable revolution.Notably,Japan has made significant advances in BM,contributing to its development through the creation of innovative materials,advanced processes,and interdisciplinary applications.However,because of certain development policies,this research has not been widely recognized on an international level.This paper provides a comprehensive summary of the research progress made by renowned Japanese laboratories and researchers in biomedical materials,bio-three-dimensional(3D)printing,and biomedical applications in the last five years.Their unique contributions are introduced and analyzed,illuminating the distinctive approaches and breakthroughs within each domain.Additionally,this review highlights the current challenges and prospects of BM.The viewpoints presented in this paper are intended to serve as a valuable reference for scholars studying BM in Japan.展开更多
Russia’s reindeer population accounts for two thirds of the world’s total.There is a strong and resilient population of reindeer on the tundra,and reindeer herders inherit and transmit the unique culture of the nort...Russia’s reindeer population accounts for two thirds of the world’s total.There is a strong and resilient population of reindeer on the tundra,and reindeer herders inherit and transmit the unique culture of the north.Reindeer products have become the subject of innovative developments in the biopharmaceutical and healthcare products industry owing to their unique raw material properties.Because deer antlers and blood are widely used in traditional Chinese medicine,significant quantities of Arctic reindeer products are likely to be sold in China.Strengthening understanding of the Russian Arctic reindeer industry will help Chinese companies invest in the Russian Arctic,promote Sino-Russian Arctic cooperation on green biomanufacturing,and lead to the development of new products that promote human health.展开更多
Recycling greenhouse gases from industrial emissions is necessary for a genuine circular carbon economy.One-carbon(C1)compounds like methanol produced from greenhouse gases and its subsequent use as a feedstock hold g...Recycling greenhouse gases from industrial emissions is necessary for a genuine circular carbon economy.One-carbon(C1)compounds like methanol produced from greenhouse gases and its subsequent use as a feedstock hold great promise in driving the next generation of biomanufacturing.This review explores the emerging field of synthetic methylotrophy,which focuses on engineering microbial cell factories to convert methanol into useful bioproducts like industrial chemicals,pharmaceuti-cals,fuels,and food.Native methylotrophs have natural pathways for methanol utilization,but obstacles such as metabolic inefficiency and the availability of genetic modification tools limit their use.In contrast,Synthetic methylotrophy makes use of model organisms such as Escherichia coli and Saccharomyces cerevisiae,which can be genetically altered to enhance the efficiency of bioconversion and methanol utilization.Although formaldehyde detoxification and enzyme optimization have improved recently due to developments in metabolic engineering,there are still many obstacles to overcome,such as limited methanol uptake and toxicity problems.The recent developments in synthetic methylotrophy are highlighted in this review,which also stresses the necessity of integrating advanced synthetic biology techniques and performing further research into metabolic pathways of methanol assimilation.Together with a consideration of the techno-economic aspects affecting the scalability of these novel processes,the potential for C1-based biomanufacturing to support sustainable production methods is emphasized.展开更多
Human activities and industrial emissions have markedly intensified the concentration of CO_(2)in the atmosphere,projected to reach 500 parts per million by 2045,thereby worsening global issues such as climate change ...Human activities and industrial emissions have markedly intensified the concentration of CO_(2)in the atmosphere,projected to reach 500 parts per million by 2045,thereby worsening global issues such as climate change and extreme weather events.To tackle these challenges,substantial efforts have been dedicated to developing efficient methods for converting the abundant and frequently underutilized one-carbon resource,such as CO_(2),to complex compounds.Currently,two main approaches exist to achieve this goal:chemical and biological methods.展开更多
Monoethanolamine(MEA)is a frequently utilized absorbent for CO_(2)capture in many settings,enabling biomanufacturing using carbon as the resource.Nevertheless,evidence indicates that MEA is toxic to biological systems...Monoethanolamine(MEA)is a frequently utilized absorbent for CO_(2)capture in many settings,enabling biomanufacturing using carbon as the resource.Nevertheless,evidence indicates that MEA is toxic to biological systems,and its emissions can exacerbate ecosystem pollution.Therefore,it is imperative that disposal or valorization measures be implemented for effective green biomanufacturing with MEA as the absorbent.This study examined the removal of MEA by Haematococcus pluvialis(H.pluvialis),an astaxanthin-rich microalgae,and its effects on microalgal cells and related mechanisms.Approximately half of the initial MEA was metabolized by H.pluvialis,with the resulting metabolic intermediates including acetyl-CoA.The genes involved in MEA utilization exhibited a significant increase in expression,signifying a pivotal advancement in our understanding of its potential as a nutrient for microalgae.Moreover,the exposure of H.pluvialis to MEA resulted in notable alterations in cellular components,including a 21.7%increase in lipid content and a 27.8% increase in carbohydrate content.Notably,there was a 1.49-fold increase in astaxanthin content,which was accompanied by notable changes in cell morphology.In addition to the increase in astaxanthin production,the antioxidant system was activated to counteract the adverse effects of MEA-induced oxidative stress.Furthermore,enhanced biosynthesis of both carotenoids and fatty acids directly contributed to the elevated cellular astaxanthin levels achieved through MEA metabolism by H.pluvialis.These findings offer valuable insights into the treatment of CO_(2)absorbents using microalgae while simultaneously producing high-value and healthy products,which may prove beneficial for the development of sustainable solutions for green biomanufacturing.展开更多
The yeast Saccharomyces cerevisiae is a well-studied unicellular eukaryote with a significant role in the biomanufacturing of natural products,biofuels,and bulk and value-added chemicals,as well as the principal model...The yeast Saccharomyces cerevisiae is a well-studied unicellular eukaryote with a significant role in the biomanufacturing of natural products,biofuels,and bulk and value-added chemicals,as well as the principal model eukaryotic organism utilized for fundamental research.Robust tools for building and optimizing yeast chassis cells were made possible by the quick development of synthetic biology,especially in engineering evolution.In this review,we focused on methods and tools from synthetic biology that are used to design and engineer S.cerevisiae's evolution.A detailed discussion was held regarding transcriptional regulation,template-dependent and template-free approaches.Furthermore,the applications of evolved S.cerevisiae were comprehensively summarized.These included improving environmental stress tolerance and raising cell metabolic performance in the production of biofuels and bulk and value-added chemicals.Finally,the future considerations were briefly discussed.展开更多
Biomanufacturing of hydrogen by acidogenic fermentation presents a promising avenue for sustainable hydrogen production;however,data on its full-scale application remain limited.Here we evaluate the performance of a 1...Biomanufacturing of hydrogen by acidogenic fermentation presents a promising avenue for sustainable hydrogen production;however,data on its full-scale application remain limited.Here we evaluate the performance of a 100 m^(3) continuous-flow stirred-tank reactor(CSTR)utilizing waste molasses and inoculated with aerobic excess sludge for hydrogen production.The reactor operated at 35℃ with a constant hydraulic retention time of 5.8 h,while the organic loading rate(OLR)was incrementally increased from 9.3 to 57.3 kg COD m^(-3)d^(-1).By day 19,stable ethanol-type fermentation was established,yielding an average of 265 m^(3) of hydrogen per day.Over the subsequent 72 days,the reactor maintained continuous operation,achieving an average hydrogen production rate of 282 m^(3) d^(-1) at an average OLR of 28.5 kg COD m^(-3)d^(-1).Bioaugmentation with Ethanoligenens harbinense YUAN-3 at a 0.5%volume fraction relative to the mixed liquor volatile suspended solids further enhanced hydrogen production to an average of 348 m^(3) d^(-1).Despite fluctuations in the OLR between 17.1 and 55.2 kg COD m^(-3)d^(-1),ethanoltype fermentation persisted throughout the bioaugmentation period.These findings demonstrate the viability of full-scale acidogenic fermentation for efficient hydrogen biomanufacturing from highstrength organic wastewater.展开更多
Space exploration and manufacturing are of critical importance for scientific advancement,technological innovation,national security,and the acquisition of extraterrestrial resources.In view of this,chemical and biolo...Space exploration and manufacturing are of critical importance for scientific advancement,technological innovation,national security,and the acquisition of extraterrestrial resources.In view of this,chemical and biological nano-/micro-/meso-scale manufacturing provide complementary approaches to overcome key space exploration challenges by enabling the in-situ production of essential life-support materials,propellants,and other resources.This review examines the origin and historical evolution of space manufacturing and the latest advances across different environments—from orbital space stations and the lunar surface to Mars and asteroids.It is structured to present the current state of research,outline key manufacturing strategies and technologies,assess the technical and environmental challenges,and discuss emerging trends and future directions.Besides,the potential applications of emerging technologies such as synthetic biology and artificial intelligence in overcoming the limitations of microgravity,limited resources,and extreme conditions are discussed.Ultimately,this integrative review could serve to guide future development,from advancing space science and disruptive manufacturing to enabling interdisciplinary and application-level innovations.展开更多
Recent years have witnessed the expansion of tissue failures and diseases.The uprising of regenerative medicine converges the sight onto stem cell-biomaterial based therapy.Tissue engineering and regenerative medicine...Recent years have witnessed the expansion of tissue failures and diseases.The uprising of regenerative medicine converges the sight onto stem cell-biomaterial based therapy.Tissue engineering and regenerative medicine proposes the strategy of constructing spatially,mechanically,chemically and biologically designed biomaterials for stem cells to grow and differentiate.Therefore,this paper summarized the basic properties of embryonic stem cells(ESCs),induced pluripotent stem cells(iPSCs)and adult stem cells.The properties of frequently used biomaterials were also described in terms of natural and synthetic origins.Particularly,the combination of stem cells and biomaterials for tissue repair applications was reviewed in terms of nervous,cardiovascular,pancreatic,hematopoietic and musculoskeletal system.Finally,stem-cell-related biomanufacturing was envisioned and the novel biofabrication technologies were discussed,enlightening a promising route for the future advancement of large-scale stem cell-biomaterial based therapeutic manufacturing.展开更多
To reduce the dependency on petroleum-based products and emission of greenhouse gas,renewable biofuels and chemicals play an important role to meet the unmatched energy demands of the rapidly growing population.Howeve...To reduce the dependency on petroleum-based products and emission of greenhouse gas,renewable biofuels and chemicals play an important role to meet the unmatched energy demands of the rapidly growing population.However,most biofuel and chemical products do not reach the commercialization stage,mainly hindered by incomparable economics to petroproducts.Techno-economic assessment(TEA)is a useful tool to estimate eco-nomic performance,and identify bottlenecks for the development of biofuel and chemical production technology,meanwhile,life cycle assessment(LCA)is applied to assess sustainability by reducing the environmental impact of biofuel and chemical production.This present review covers TEA and LCA research progress in the manufacturing of biofuels and biochemical,and discusses the impacts of TEA and LCA results on the development and optimi-zation of biofuel and chemical production.In addition,challenges associated with TEA and LCA of biofuel and biochemical production were briefly overviewed,and potential approaches that may overcome such challenges were discussed enabling viable and sustainable biomanufacturing of fuels and chemicals.Future integrated TEA and LCA studies could significantly promote the economic and sustainable development of the biomanufacturing process.展开更多
Developing efficient CO_(2)utilization technologies can alleviate the urgent pressure on energy and the environment.Moreover,these technologies are crucial for achieving the goal of net zero emissions.Microalgae are p...Developing efficient CO_(2)utilization technologies can alleviate the urgent pressure on energy and the environment.Moreover,these technologies are crucial for achieving the goal of net zero emissions.Microalgae are photoautotrophic microorganisms that are the main sources of primary productivity in the biosphere.Cyanobacteria,the only prokaryotic microalgae,have also been considered as promising chassis for photosynthetic biosynthesis,directly converting solar energy and CO_(2)into various bio-based products.This technological route is called photosynthetic biomanufacturing,and is advantageous to simultaneous carbon fixation and clean production.This review focuses on development mode,application and suggests trends related to the further development of photosynthetic biomanufacturing.With regard to the link between photosynthetic CO_(2)fixation and the production of desired metabolites,we summarized and compared three widely adopted strategies.“Screening to find”,screening a large number of high-quality cyanobacterial resources and analyzing their intracellular metabolites are of significance for screening novel cyanobacterial species with high-value chemicals and properties of industrial relevance.“Engineering to modify”,the emergence and application of synthetic biological tools and metabolic engineering strategies have enhanced the ability to modify different cyanobacterial species to reshape more carbon to flow toward synthetic tailored chemicals.“Stressing to activate”,through special culture conditions and strategies,combined with omics analysis techniques,silent metabolic pathways and functional modules are activated to induce the accumulation of high-value chemicals.This review provides valid and updated information to facilitate the development of photosynthetic biosynthesis route with carbon fixation and clean production,providing specific feasible solutions for net zero emissions.展开更多
Although most in vitro(cell-free)synthetic biology projects are usually used for the purposes of fundamental research or the formation of high-value products,in vitro synthetic biology platform,which can implement com...Although most in vitro(cell-free)synthetic biology projects are usually used for the purposes of fundamental research or the formation of high-value products,in vitro synthetic biology platform,which can implement complicated biochemical reactions by the in vitro assembly of numerous enzymes and coenzymes,has been proposed for low-cost biomanufacturing of bioenergy,food,biochemicals,and nutraceuticals.In addition to the most important advantage-high product yield,in vitro synthetic biology platform features several other biomanufacturing advantages,such as fast reaction rate,easy product separation,open process control,broad reaction condition,tolerance to toxic substrates or products,and so on.In this article,we present the basic bottom-up design principles of in vitro synthetic pathway from basic building blocks-BioBricks(thermoenzymes and/or immobilized enzymes)to building modules(e.g.,enzyme complexes or multiple enzymes as a module)with specific functions.With development in thermostable building blocks-BioBricks and modules,the in vitro synthetic biology platform would open a new biomanufacturing age for the cost-competitive production of biocommodities.展开更多
The domain of industrial biomanufacturing is enthusiastically embracing the concept of Digital Twin,owing to its promises of increased process efficiency and resource utilisation.However,Digital Twin in biomanufacturi...The domain of industrial biomanufacturing is enthusiastically embracing the concept of Digital Twin,owing to its promises of increased process efficiency and resource utilisation.However,Digital Twin in biomanufacturing is not yet clearly defined and this sector of the industry is falling behind the others in terms of its implementation.On the other hand,some of the benefits of Digital Twin seem to overlap with the more established practices of process control and optimization,and the term is vaguely used in different scenarios.In an attempt to clarify this issue,we investigate this overlap for the specific case of fermentation operation,a central step in many biomanufacturing processes.Based on this investigation,a framework built upon a five-step pathway starting from a basic steady-state process model is proposed to develop a fully-fledged Digital Twin.For demonstration purposes,the framework is applied to a bench-scale second-generation ethanol fermentation process as a case study.It is proposed that the success or failure of a fully-fledged Digital Twin implementation is determined by key factors that comprise the role of modelling,human operator actions,and other propositions of economic value.展开更多
Translation of any inventions into products requires manufacturing.Development of drug/gene/cell delivery systems will eventually face manufacturing challenges,which require the establishment of standardized processes...Translation of any inventions into products requires manufacturing.Development of drug/gene/cell delivery systems will eventually face manufacturing challenges,which require the establishment of standardized processes to produce biologically-relevant products of high quality without incurring prohibitive cost.Microfluidicu technologies present many advantages to improve the quality of drug/gene/cell delivery systems.They also offer the benefits of automation.What remains unclear is whether they can meet the scale-up requirement.In this perspective,we discuss the advantages of microfluidic-assisted synthesis of nanoscale drug/gene delivery systems,formation of microscale drug/cell-encapsulated particles,generation of genetically engineered cells and fabrication of macroscale drug/cell-loaded micro-/nano-fibers.We also highlight the scale-up challenges one would face in adopting microfluidic technologies for the manufacturing of these therapeutic delivery systems.展开更多
Biomanufacturing relies on living cells to produce biotechnology-based therapeutics,tissue engineering constructs,vaccines,and a vast range of agricultural and industrial products.With the escalating demand for these ...Biomanufacturing relies on living cells to produce biotechnology-based therapeutics,tissue engineering constructs,vaccines,and a vast range of agricultural and industrial products.With the escalating demand for these bio-based products,any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline.While these goals are primarily achieved using biological or chemical strategies,harnessing cell mechanosensitivity represents a promising–albeit less studied–physical pathway to promote bioprocessing endpoints,yet identifying which mechanical parameters influence cell activities has remained elusive.We tested the hypothesis that mechanical signals,delivered non-invasively using low-intensity vibration(LIV;<1 g,10–500 Hz),will enhance cell expansion,and determined that any unique signal configuration was not equally influential across a range of cell types.Varying frequency,intensity,duration,refractory period,and daily doses of LIV increased proliferation in Chinese Hamster Ovary(CHO)-adherent cells(t79%in 96 hr)using a particular set of LIV parameters(0.2 g,500 Hz,3-30 min/d,2 hr refractory period),yet this same mechanical input suppressed proliferation in CHO-suspension cells(-13%).Another set of LIV parameters(30 Hz,0.7 g,2-60 min/d,2 hr refractory period)however,were able to increase the proliferation of CHO-suspension cells by 210%and T-cells by 20.3%.Importantly,we also reported that T-cell response to LIV was in-part dependent upon AKT phosphorylation,as inhibiting AKT phosphorylation reduced the proliferative effect of LIV by over 60%,suggesting that suspension cells utilize mechanism(s)similar to adherent cells to sense specific LIV signals.Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids(>90%),and LIV effectively scaled up to T75 flasks.Ultimately,when LIV is tailored to the target cell population,it's highly efficient transmission across media represents a means to noninvasively augment biomanufacturing endpoints for both adherent and suspended cells,and holds immediate applications,ranging from small-scale,patient-specific personalized medicine to large-scale commercial biocentric production challenges.展开更多
Inactivated cell catalysis is one of several central techniques in green biomanufacturing realm.However,the instability and leakage of enzymes in inactivated cell severely restrict the practical applications of inacti...Inactivated cell catalysis is one of several central techniques in green biomanufacturing realm.However,the instability and leakage of enzymes in inactivated cell severely restrict the practical applications of inactivated cell catalysis.Constructing armor on the surface of inactivated cells affords a feasible and effective strategy to enhance the stability of cells while commonly lowering the permeability.Herein,polymer-silica hybrid armor(PSHA)is directly generated on the surface of enzyme-containing cells.The branched structure of PEI enables higher porosity of cell@PSHA,exhibiting 1.52-fold enhancement in substrate permeability by contrast with cell@silica armor(SA).The electrostatic interactions(NH_(3)^(+)with O^(−))and hydrogen bonding(N⋯H or O⋯H)interactions between structural units enables higher stability of cell@PSHA,showing 3.13-fold elevation in Young's modulus compared with cell@SA.As a result,the cell@PSHA can catalyze continuous conversion of starch to tagatose for 15 batches over 969 h,with an average yield of 77.76 g L^(−1).展开更多
The designing and manufacturing of micro/nanoscale tools for delivery,diagnostic,and therapeutic are essential for their multiscale integration in the precision medicine field.Conventional three-dimensional(3D)printin...The designing and manufacturing of micro/nanoscale tools for delivery,diagnostic,and therapeutic are essential for their multiscale integration in the precision medicine field.Conventional three-dimensional(3D)printing approaches are not suitable for such kind of tools due to the accuracy limitation.Multiphoton polymerization(MPP)-based micro/nanomanufacturing is a noncontact,high-precision molding technology that has been widely used in the micro/nano field is a promising tool for micro/nanoscale related precision medicine.In this article the fundamentals of MPP-based technology and the required materials in precision medicine are overviewed.The biomedical applications in various scenarios are then summarized and categorized as delivery systems,microtissue modeling,surgery,and diagnosis.Finally,the existing challenges and future perspectives on MPP-based micro/nanomanufacturing for precision medicine are discussed,focusing on material design,process optimization,and practical applications to overcome its current limitations.展开更多
Bone cancer is a critical health problem on a global scale,and the associated huge clinical and economic burdens are still rising.Although many clinical approaches are currently used for bone cancer treatment,these me...Bone cancer is a critical health problem on a global scale,and the associated huge clinical and economic burdens are still rising.Although many clinical approaches are currently used for bone cancer treatment,these methods usually affect the normal body functions and thus present significant limitations.Meanwhile,advanced materials and additive manufacturing have opened up promising avenues for the development of new strategies targeting both bone cancer treatment and post-treatment bone regeneration.This paper presents a comprehensive review of bone cancer and its current treatment methods,particularly focusing on a number of advanced strategies such as scaffolds based on advanced functional materials,drug-loaded scaffolds,and scaffolds for photothermal/magnetothermal therapy.Finally,the main research challenges and future perspectives are elaborated.展开更多
Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical printing.It has also been ...Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical printing.It has also been employed in various advanced industrial areas.The development of intelligent biomedical engineering has raised the requirements for 3D printing,such as flexible manufacturing processes and technologies,biocompatible constituents,and alternative bioproducts.However,state-of-the-art 3D printing mainly involves inorganics or polymers and generally focuses on traditional industrial fields,thus severely limiting applications demanding biocompatibility and biodegradability.In this regard,peptide architectonics,which are self-assembled by programmed amino acid sequences that can be flexibly functionalized,have shown promising potential as bioinspired inks for 3D printing.Therefore,the combination of 3D printing and peptide self-assembly poten-tially opens up an alternative avenue of 3D bioprinting for diverse advanced applications.Israel,a small but innovative nation,has significantly contributed to 3D bioprinting in terms of scientific studies,marketization,and peptide architectonics,including modulations and applications,and ranks as a leading area in the 3D bioprinting field.This review summarizes the recent progress in 3D bioprinting in Israel,focusing on scientific studies on printable components,soft devices,and tissue engineering.This paper further delves into the manufacture of industrial products,such as artificial meats and bioinspired supramolecular architectures,and the mechanisms,physicochemical properties,and applications of peptide self-assembly.Undoubtedly,Israel contributes significantly to the field of 3D bioprinting and should thus be appropriately recognized.展开更多
基金support from the National Nat-ural Science Foundation of China(U1663227,21861132017,21811530003,21878170).
文摘Biomanufacturing,which uses renewable resources as raw materials and uses biological processes to produce energy and chemicals,has long been regarded as a production model that replaces the unsustainable fossil economy.The construction of non-natural and efficient biosynthesis routes of chemicals is an important goal of green biomanufacturing.Traditional methods that rely on experience are difficult to support the realization of this goal.However,with the rapid development of information technology,the intelligence of biomanufacturing has brought hope to achieve this goal.Retrobiosynthesis and computational enzyme design,as two of the main technologies in intelligent biomanufacturing,have developed rapidly in recent years and have made great achievements and some representative works have demonstrated the great value that the integration of the two fields may bring.To achieve the final integration of the two fields,it is necessary to examine the information,methods and tools from a bird’s-eye view,and to find a feasible idea and solution for establishing a connection point.For this purpose,this article briefly reviewed the main ideas,methods and tools of the two fields,and put forward views on how to achieve the integration of the two fields.
基金This work was supported by the National Natural Science Foundation of China(No.52105072).
文摘Biomanufacturing(BM)is a multidisciplinary area incorporating the characteristics of living organisms and engineering principles to create valuable products for various sectors,including medicine,energy,and the environment.BM has undergone a remarkable transformation in the last two decades,entering the era of BM4.0 and becoming a pivotal driver of the sustainable revolution.Notably,Japan has made significant advances in BM,contributing to its development through the creation of innovative materials,advanced processes,and interdisciplinary applications.However,because of certain development policies,this research has not been widely recognized on an international level.This paper provides a comprehensive summary of the research progress made by renowned Japanese laboratories and researchers in biomedical materials,bio-three-dimensional(3D)printing,and biomedical applications in the last five years.Their unique contributions are introduced and analyzed,illuminating the distinctive approaches and breakthroughs within each domain.Additionally,this review highlights the current challenges and prospects of BM.The viewpoints presented in this paper are intended to serve as a valuable reference for scholars studying BM in Japan.
基金a phased result of both the research on“Strategic Competition and Cooperation in the Arctic among China,Russia,and the United States from the Perspective of Sustainable Development”(Grant no.20BGJ045)the research project on the fusion of Arctic biological resource products and traditional Chinese medicine culture(Grant no.21JD004A)。
文摘Russia’s reindeer population accounts for two thirds of the world’s total.There is a strong and resilient population of reindeer on the tundra,and reindeer herders inherit and transmit the unique culture of the north.Reindeer products have become the subject of innovative developments in the biopharmaceutical and healthcare products industry owing to their unique raw material properties.Because deer antlers and blood are widely used in traditional Chinese medicine,significant quantities of Arctic reindeer products are likely to be sold in China.Strengthening understanding of the Russian Arctic reindeer industry will help Chinese companies invest in the Russian Arctic,promote Sino-Russian Arctic cooperation on green biomanufacturing,and lead to the development of new products that promote human health.
文摘Recycling greenhouse gases from industrial emissions is necessary for a genuine circular carbon economy.One-carbon(C1)compounds like methanol produced from greenhouse gases and its subsequent use as a feedstock hold great promise in driving the next generation of biomanufacturing.This review explores the emerging field of synthetic methylotrophy,which focuses on engineering microbial cell factories to convert methanol into useful bioproducts like industrial chemicals,pharmaceuti-cals,fuels,and food.Native methylotrophs have natural pathways for methanol utilization,but obstacles such as metabolic inefficiency and the availability of genetic modification tools limit their use.In contrast,Synthetic methylotrophy makes use of model organisms such as Escherichia coli and Saccharomyces cerevisiae,which can be genetically altered to enhance the efficiency of bioconversion and methanol utilization.Although formaldehyde detoxification and enzyme optimization have improved recently due to developments in metabolic engineering,there are still many obstacles to overcome,such as limited methanol uptake and toxicity problems.The recent developments in synthetic methylotrophy are highlighted in this review,which also stresses the necessity of integrating advanced synthetic biology techniques and performing further research into metabolic pathways of methanol assimilation.Together with a consideration of the techno-economic aspects affecting the scalability of these novel processes,the potential for C1-based biomanufacturing to support sustainable production methods is emphasized.
基金supported by the National Natural Science Foundation of China(22378166)the Basic Research Program of Jiangsu and Jiangsu Basic Research Center for Synthetic Biology(BK20233003)+1 种基金the Fundamental Research Funds for the Central Universities(JUSRP622001)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX24_2583).
文摘Human activities and industrial emissions have markedly intensified the concentration of CO_(2)in the atmosphere,projected to reach 500 parts per million by 2045,thereby worsening global issues such as climate change and extreme weather events.To tackle these challenges,substantial efforts have been dedicated to developing efficient methods for converting the abundant and frequently underutilized one-carbon resource,such as CO_(2),to complex compounds.Currently,two main approaches exist to achieve this goal:chemical and biological methods.
基金supported by the National Key R&D Program of China(2022YFC3401800)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDC0120301)+5 种基金the National Natural Science Foundation of China(32470253)the Hundred Talents Program of the Chinese Academy of Sciences(E3J56201)the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-IJCP-001TSBICIP-IJCP-002TSBICIP-CXRC-027)the Tangshan Science and Technology Program(24150214C).
文摘Monoethanolamine(MEA)is a frequently utilized absorbent for CO_(2)capture in many settings,enabling biomanufacturing using carbon as the resource.Nevertheless,evidence indicates that MEA is toxic to biological systems,and its emissions can exacerbate ecosystem pollution.Therefore,it is imperative that disposal or valorization measures be implemented for effective green biomanufacturing with MEA as the absorbent.This study examined the removal of MEA by Haematococcus pluvialis(H.pluvialis),an astaxanthin-rich microalgae,and its effects on microalgal cells and related mechanisms.Approximately half of the initial MEA was metabolized by H.pluvialis,with the resulting metabolic intermediates including acetyl-CoA.The genes involved in MEA utilization exhibited a significant increase in expression,signifying a pivotal advancement in our understanding of its potential as a nutrient for microalgae.Moreover,the exposure of H.pluvialis to MEA resulted in notable alterations in cellular components,including a 21.7%increase in lipid content and a 27.8% increase in carbohydrate content.Notably,there was a 1.49-fold increase in astaxanthin content,which was accompanied by notable changes in cell morphology.In addition to the increase in astaxanthin production,the antioxidant system was activated to counteract the adverse effects of MEA-induced oxidative stress.Furthermore,enhanced biosynthesis of both carotenoids and fatty acids directly contributed to the elevated cellular astaxanthin levels achieved through MEA metabolism by H.pluvialis.These findings offer valuable insights into the treatment of CO_(2)absorbents using microalgae while simultaneously producing high-value and healthy products,which may prove beneficial for the development of sustainable solutions for green biomanufacturing.
基金supported by the National Key Research and Development Program of China(2021YFC2103300)National Natural Science Foundation of China(32161133019 and 32200067)+3 种基金Major Science and Technology Support Program Project in Hebei Province(24292902Z)Key Research and Development Program Projects of Hebei Province(22322905D)Industry University Research Cooperation Project of Shijiazhuang and University of Hebei province(241490062A)supported by Tianjin Industrial Synthetic Biology Innovation Team.
文摘The yeast Saccharomyces cerevisiae is a well-studied unicellular eukaryote with a significant role in the biomanufacturing of natural products,biofuels,and bulk and value-added chemicals,as well as the principal model eukaryotic organism utilized for fundamental research.Robust tools for building and optimizing yeast chassis cells were made possible by the quick development of synthetic biology,especially in engineering evolution.In this review,we focused on methods and tools from synthetic biology that are used to design and engineer S.cerevisiae's evolution.A detailed discussion was held regarding transcriptional regulation,template-dependent and template-free approaches.Furthermore,the applications of evolved S.cerevisiae were comprehensively summarized.These included improving environmental stress tolerance and raising cell metabolic performance in the production of biofuels and bulk and value-added chemicals.Finally,the future considerations were briefly discussed.
基金supported by the National High Technology Research and Development Program of China(863 program,Grant No.2003AA515030 and 2011AA060905)the Harbin Chenergy Gongda Environmental Technology Co.,Ltd。
文摘Biomanufacturing of hydrogen by acidogenic fermentation presents a promising avenue for sustainable hydrogen production;however,data on its full-scale application remain limited.Here we evaluate the performance of a 100 m^(3) continuous-flow stirred-tank reactor(CSTR)utilizing waste molasses and inoculated with aerobic excess sludge for hydrogen production.The reactor operated at 35℃ with a constant hydraulic retention time of 5.8 h,while the organic loading rate(OLR)was incrementally increased from 9.3 to 57.3 kg COD m^(-3)d^(-1).By day 19,stable ethanol-type fermentation was established,yielding an average of 265 m^(3) of hydrogen per day.Over the subsequent 72 days,the reactor maintained continuous operation,achieving an average hydrogen production rate of 282 m^(3) d^(-1) at an average OLR of 28.5 kg COD m^(-3)d^(-1).Bioaugmentation with Ethanoligenens harbinense YUAN-3 at a 0.5%volume fraction relative to the mixed liquor volatile suspended solids further enhanced hydrogen production to an average of 348 m^(3) d^(-1).Despite fluctuations in the OLR between 17.1 and 55.2 kg COD m^(-3)d^(-1),ethanoltype fermentation persisted throughout the bioaugmentation period.These findings demonstrate the viability of full-scale acidogenic fermentation for efficient hydrogen biomanufacturing from highstrength organic wastewater.
基金supported by National Natural Science Foundation of China(22278241)a grant from the Institute Guo Qiang,Tsinghua University(2021GQG1016).
文摘Space exploration and manufacturing are of critical importance for scientific advancement,technological innovation,national security,and the acquisition of extraterrestrial resources.In view of this,chemical and biological nano-/micro-/meso-scale manufacturing provide complementary approaches to overcome key space exploration challenges by enabling the in-situ production of essential life-support materials,propellants,and other resources.This review examines the origin and historical evolution of space manufacturing and the latest advances across different environments—from orbital space stations and the lunar surface to Mars and asteroids.It is structured to present the current state of research,outline key manufacturing strategies and technologies,assess the technical and environmental challenges,and discuss emerging trends and future directions.Besides,the potential applications of emerging technologies such as synthetic biology and artificial intelligence in overcoming the limitations of microgravity,limited resources,and extreme conditions are discussed.Ultimately,this integrative review could serve to guide future development,from advancing space science and disruptive manufacturing to enabling interdisciplinary and application-level innovations.
文摘Recent years have witnessed the expansion of tissue failures and diseases.The uprising of regenerative medicine converges the sight onto stem cell-biomaterial based therapy.Tissue engineering and regenerative medicine proposes the strategy of constructing spatially,mechanically,chemically and biologically designed biomaterials for stem cells to grow and differentiate.Therefore,this paper summarized the basic properties of embryonic stem cells(ESCs),induced pluripotent stem cells(iPSCs)and adult stem cells.The properties of frequently used biomaterials were also described in terms of natural and synthetic origins.Particularly,the combination of stem cells and biomaterials for tissue repair applications was reviewed in terms of nervous,cardiovascular,pancreatic,hematopoietic and musculoskeletal system.Finally,stem-cell-related biomanufacturing was envisioned and the novel biofabrication technologies were discussed,enlightening a promising route for the future advancement of large-scale stem cell-biomaterial based therapeutic manufacturing.
基金supported by the National Key Research and Development Program of China(2021YFC2103500)the National Natural Science Foundation of China(21878241,22178281)the Science Fund for Distinguished Young Scholars of Shaanxi Province(2022JC-09).
文摘To reduce the dependency on petroleum-based products and emission of greenhouse gas,renewable biofuels and chemicals play an important role to meet the unmatched energy demands of the rapidly growing population.However,most biofuel and chemical products do not reach the commercialization stage,mainly hindered by incomparable economics to petroproducts.Techno-economic assessment(TEA)is a useful tool to estimate eco-nomic performance,and identify bottlenecks for the development of biofuel and chemical production technology,meanwhile,life cycle assessment(LCA)is applied to assess sustainability by reducing the environmental impact of biofuel and chemical production.This present review covers TEA and LCA research progress in the manufacturing of biofuels and biochemical,and discusses the impacts of TEA and LCA results on the development and optimi-zation of biofuel and chemical production.In addition,challenges associated with TEA and LCA of biofuel and biochemical production were briefly overviewed,and potential approaches that may overcome such challenges were discussed enabling viable and sustainable biomanufacturing of fuels and chemicals.Future integrated TEA and LCA studies could significantly promote the economic and sustainable development of the biomanufacturing process.
基金supported by the National Key Research and Development Program of China(Grant number 2021YFA0909700,to X.L.and G.L.)the Youth Innovation Promotion Association CAS(to G.L.)+2 种基金the National Natural Science Foundation of China(Grant number 32070084 to G.L.,32270103 to G.L.,32271484 to X.L.,32300058 to J.C.)the DNL Cooperation Fund,CAS(DNL202014,to G.L.)the Shandong Taishan Scholarship(to X.L.and G.L.).
文摘Developing efficient CO_(2)utilization technologies can alleviate the urgent pressure on energy and the environment.Moreover,these technologies are crucial for achieving the goal of net zero emissions.Microalgae are photoautotrophic microorganisms that are the main sources of primary productivity in the biosphere.Cyanobacteria,the only prokaryotic microalgae,have also been considered as promising chassis for photosynthetic biosynthesis,directly converting solar energy and CO_(2)into various bio-based products.This technological route is called photosynthetic biomanufacturing,and is advantageous to simultaneous carbon fixation and clean production.This review focuses on development mode,application and suggests trends related to the further development of photosynthetic biomanufacturing.With regard to the link between photosynthetic CO_(2)fixation and the production of desired metabolites,we summarized and compared three widely adopted strategies.“Screening to find”,screening a large number of high-quality cyanobacterial resources and analyzing their intracellular metabolites are of significance for screening novel cyanobacterial species with high-value chemicals and properties of industrial relevance.“Engineering to modify”,the emergence and application of synthetic biological tools and metabolic engineering strategies have enhanced the ability to modify different cyanobacterial species to reshape more carbon to flow toward synthetic tailored chemicals.“Stressing to activate”,through special culture conditions and strategies,combined with omics analysis techniques,silent metabolic pathways and functional modules are activated to induce the accumulation of high-value chemicals.This review provides valid and updated information to facilitate the development of photosynthetic biosynthesis route with carbon fixation and clean production,providing specific feasible solutions for net zero emissions.
基金the National Natural Science Foundation of China(Grant No.31700033)the Key Research Program of the Chinese Academy of Sciences(Grant No.ZDRW-ZS-2016-3).
文摘Although most in vitro(cell-free)synthetic biology projects are usually used for the purposes of fundamental research or the formation of high-value products,in vitro synthetic biology platform,which can implement complicated biochemical reactions by the in vitro assembly of numerous enzymes and coenzymes,has been proposed for low-cost biomanufacturing of bioenergy,food,biochemicals,and nutraceuticals.In addition to the most important advantage-high product yield,in vitro synthetic biology platform features several other biomanufacturing advantages,such as fast reaction rate,easy product separation,open process control,broad reaction condition,tolerance to toxic substrates or products,and so on.In this article,we present the basic bottom-up design principles of in vitro synthetic pathway from basic building blocks-BioBricks(thermoenzymes and/or immobilized enzymes)to building modules(e.g.,enzyme complexes or multiple enzymes as a module)with specific functions.With development in thermostable building blocks-BioBricks and modules,the in vitro synthetic biology platform would open a new biomanufacturing age for the cost-competitive production of biocommodities.
基金The work is funded by the Novo Nordisk Foundation in the frame of the‘Accelerated Innovation in Manufacturing Biologics’(AIMBio)project(Grant number NNF19SA0035474).
文摘The domain of industrial biomanufacturing is enthusiastically embracing the concept of Digital Twin,owing to its promises of increased process efficiency and resource utilisation.However,Digital Twin in biomanufacturing is not yet clearly defined and this sector of the industry is falling behind the others in terms of its implementation.On the other hand,some of the benefits of Digital Twin seem to overlap with the more established practices of process control and optimization,and the term is vaguely used in different scenarios.In an attempt to clarify this issue,we investigate this overlap for the specific case of fermentation operation,a central step in many biomanufacturing processes.Based on this investigation,a framework built upon a five-step pathway starting from a basic steady-state process model is proposed to develop a fully-fledged Digital Twin.For demonstration purposes,the framework is applied to a bench-scale second-generation ethanol fermentation process as a case study.It is proposed that the success or failure of a fully-fledged Digital Twin implementation is determined by key factors that comprise the role of modelling,human operator actions,and other propositions of economic value.
基金This work was supported from NIH(4UH3TR000505,AI096305,HL109442)the NIH Common Fund for the Microphysiological Systems Initiative is acknowledged.H.F.C.is grateful for fellowship support from the Sir Edward Youde Memorial Fund Council(Hong Kong).
文摘Translation of any inventions into products requires manufacturing.Development of drug/gene/cell delivery systems will eventually face manufacturing challenges,which require the establishment of standardized processes to produce biologically-relevant products of high quality without incurring prohibitive cost.Microfluidicu technologies present many advantages to improve the quality of drug/gene/cell delivery systems.They also offer the benefits of automation.What remains unclear is whether they can meet the scale-up requirement.In this perspective,we discuss the advantages of microfluidic-assisted synthesis of nanoscale drug/gene delivery systems,formation of microscale drug/cell-encapsulated particles,generation of genetically engineered cells and fabrication of macroscale drug/cell-loaded micro-/nano-fibers.We also highlight the scale-up challenges one would face in adopting microfluidic technologies for the manufacturing of these therapeutic delivery systems.
基金supported by the Long Island Bioscience Hub funded through the NIH-Research Evaluation and Commercialization Hub(U-HL127522)the Research Foundation Technology Accelerator Fund,the Center for Biotechnology(NYSTAR)as well as grants from NIH(AG059923,P20GM109095)and NSF(1929188&2025505).
文摘Biomanufacturing relies on living cells to produce biotechnology-based therapeutics,tissue engineering constructs,vaccines,and a vast range of agricultural and industrial products.With the escalating demand for these bio-based products,any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline.While these goals are primarily achieved using biological or chemical strategies,harnessing cell mechanosensitivity represents a promising–albeit less studied–physical pathway to promote bioprocessing endpoints,yet identifying which mechanical parameters influence cell activities has remained elusive.We tested the hypothesis that mechanical signals,delivered non-invasively using low-intensity vibration(LIV;<1 g,10–500 Hz),will enhance cell expansion,and determined that any unique signal configuration was not equally influential across a range of cell types.Varying frequency,intensity,duration,refractory period,and daily doses of LIV increased proliferation in Chinese Hamster Ovary(CHO)-adherent cells(t79%in 96 hr)using a particular set of LIV parameters(0.2 g,500 Hz,3-30 min/d,2 hr refractory period),yet this same mechanical input suppressed proliferation in CHO-suspension cells(-13%).Another set of LIV parameters(30 Hz,0.7 g,2-60 min/d,2 hr refractory period)however,were able to increase the proliferation of CHO-suspension cells by 210%and T-cells by 20.3%.Importantly,we also reported that T-cell response to LIV was in-part dependent upon AKT phosphorylation,as inhibiting AKT phosphorylation reduced the proliferative effect of LIV by over 60%,suggesting that suspension cells utilize mechanism(s)similar to adherent cells to sense specific LIV signals.Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids(>90%),and LIV effectively scaled up to T75 flasks.Ultimately,when LIV is tailored to the target cell population,it's highly efficient transmission across media represents a means to noninvasively augment biomanufacturing endpoints for both adherent and suspended cells,and holds immediate applications,ranging from small-scale,patient-specific personalized medicine to large-scale commercial biocentric production challenges.
基金the National Key Research and Development Program of China(grant No.2021YFC2102300)National Natural Science Foundation of China(grant No.22122809)+2 种基金Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(grant No.TSBICIP-KJGG-003)Open Funding Project of the State Key Laboratory of Biochemical Engineering,China(grant No.2020 KF-06)Haihe Laboratory of Sustainable Chemical Transformations,and Program of Introducing Talents of Discipline to。
文摘Inactivated cell catalysis is one of several central techniques in green biomanufacturing realm.However,the instability and leakage of enzymes in inactivated cell severely restrict the practical applications of inactivated cell catalysis.Constructing armor on the surface of inactivated cells affords a feasible and effective strategy to enhance the stability of cells while commonly lowering the permeability.Herein,polymer-silica hybrid armor(PSHA)is directly generated on the surface of enzyme-containing cells.The branched structure of PEI enables higher porosity of cell@PSHA,exhibiting 1.52-fold enhancement in substrate permeability by contrast with cell@silica armor(SA).The electrostatic interactions(NH_(3)^(+)with O^(−))and hydrogen bonding(N⋯H or O⋯H)interactions between structural units enables higher stability of cell@PSHA,showing 3.13-fold elevation in Young's modulus compared with cell@SA.As a result,the cell@PSHA can catalyze continuous conversion of starch to tagatose for 15 batches over 969 h,with an average yield of 77.76 g L^(−1).
基金the National Natural Science Foundation of China(52275294)the National Key Research and Development Program of China(2018YFA0703000).
文摘The designing and manufacturing of micro/nanoscale tools for delivery,diagnostic,and therapeutic are essential for their multiscale integration in the precision medicine field.Conventional three-dimensional(3D)printing approaches are not suitable for such kind of tools due to the accuracy limitation.Multiphoton polymerization(MPP)-based micro/nanomanufacturing is a noncontact,high-precision molding technology that has been widely used in the micro/nano field is a promising tool for micro/nanoscale related precision medicine.In this article the fundamentals of MPP-based technology and the required materials in precision medicine are overviewed.The biomedical applications in various scenarios are then summarized and categorized as delivery systems,microtissue modeling,surgery,and diagnosis.Finally,the existing challenges and future perspectives on MPP-based micro/nanomanufacturing for precision medicine are discussed,focusing on material design,process optimization,and practical applications to overcome its current limitations.
基金the Engineering and Physical Sciences Research Council(EPSRC)UK through the Global Challenges Research Fund(No.EP/R015139/1)Rosetrees&Stoneygate Trust Enterprise Fellowship(Ref:A2750/M874)from Rosetrees Trust UK and Stoneygate Trust UK.
文摘Bone cancer is a critical health problem on a global scale,and the associated huge clinical and economic burdens are still rising.Although many clinical approaches are currently used for bone cancer treatment,these methods usually affect the normal body functions and thus present significant limitations.Meanwhile,advanced materials and additive manufacturing have opened up promising avenues for the development of new strategies targeting both bone cancer treatment and post-treatment bone regeneration.This paper presents a comprehensive review of bone cancer and its current treatment methods,particularly focusing on a number of advanced strategies such as scaffolds based on advanced functional materials,drug-loaded scaffolds,and scaffolds for photothermal/magnetothermal therapy.Finally,the main research challenges and future perspectives are elaborated.
基金supported by the National Key R&D Program of China within the China-Israel Cooperative Scientific Research(No.2022YFE0100800)(Israeli No.3-18130)the National Natural Science Foundation of China(Nos.52175551,22072181)+1 种基金the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang Province,China(No.2022R01001)the Zhejiang University Global Partnership Fund and Open Foundation of the State Key Laboratory of Fluid Power and Mechatronic Systems(No.GZKF-202224).
文摘Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical printing.It has also been employed in various advanced industrial areas.The development of intelligent biomedical engineering has raised the requirements for 3D printing,such as flexible manufacturing processes and technologies,biocompatible constituents,and alternative bioproducts.However,state-of-the-art 3D printing mainly involves inorganics or polymers and generally focuses on traditional industrial fields,thus severely limiting applications demanding biocompatibility and biodegradability.In this regard,peptide architectonics,which are self-assembled by programmed amino acid sequences that can be flexibly functionalized,have shown promising potential as bioinspired inks for 3D printing.Therefore,the combination of 3D printing and peptide self-assembly poten-tially opens up an alternative avenue of 3D bioprinting for diverse advanced applications.Israel,a small but innovative nation,has significantly contributed to 3D bioprinting in terms of scientific studies,marketization,and peptide architectonics,including modulations and applications,and ranks as a leading area in the 3D bioprinting field.This review summarizes the recent progress in 3D bioprinting in Israel,focusing on scientific studies on printable components,soft devices,and tissue engineering.This paper further delves into the manufacture of industrial products,such as artificial meats and bioinspired supramolecular architectures,and the mechanisms,physicochemical properties,and applications of peptide self-assembly.Undoubtedly,Israel contributes significantly to the field of 3D bioprinting and should thus be appropriately recognized.
