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  • Synthetic Biochemistry: The Bio-inspired Cell-Free Approach to Commodity Chemical Production
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-23
    James U. Bowie; Saken Sherkhanov; Tyler P. Korman; Meaghan A. Valliere; Paul H. Opgenorth; Hongjiang Liu

    Metabolic engineering efforts that harness living organisms to produce natural products and other useful chemicals face inherent difficulties because the maintenance of life processes often runs counter to our desire to maximize important production metrics. These challenges are particularly problematic for commodity chemical manufacturing where cost is critical. A cell-free approach, where biochemical pathways are built by mixing desired enzyme activities outside of cells, can obviate problems associated with cell-based methods. Yet supplanting cell-based methods of chemical production will require the creation of self-sustaining, continuously operating systems where input biomass is converted into desired products at high yields, productivities, and titers. We call the field of designing and implementing reliable and efficient enzyme systems that replace cellular metabolism, synthetic biochemistry.

  • Toward an Optimized Process for Clinical Manufacturing of CAR-Treg Cell Therapy
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-22
    Enrico Fritsche; Hans-Dieter Volk; Petra Reinke; Mohamed Abou-El-Enein

    Chimeric antigen receptor (CAR) technology and its application to regulatory T cells (Tregs) has been hailed as the next scientific breakthrough in the field of cell and gene therapy. Merging the benefits of CAR technology with Tregs offers a novel and promising therapeutic option for durable reshaping of undesired immune responses following solid organ or hematopoietic stem cell transplantation, as well as in immune-related disorders. However, major challenges remain for developing a standardized, robust, and reliable good manufacturing practice (GMP)-compliant manufacturing process for CAR-Treg cells. We review current progress in the field and recommend ways to improve current CAR-Treg manufacturing processes based on lessons learned from first-generation Treg therapeutics as well as from anticancer CAR-T cell development.

  • Enabling Technologies for Personalized and Precision Medicine
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-21
    Dean Ho; Stephen R. Quake; Edward R.B. McCabe; Wee Joo Chng; Edward K. Chow; Xianting Ding; Bruce D. Gelb; Geoffrey S. Ginsburg; Jason Hassenstab; Chih-Ming Ho; William C. Mobley; Garry P. Nolan; Steven T. Rosen; Patrick Tan; Yun Yen; Ali Zarrinpar

    Individualizing patient treatment is a core objective of the medical field. Reaching this objective has been elusive owing to the complex set of factors contributing to both disease and health; many factors, from genes to proteins, remain unknown in their role in human physiology. Accurately diagnosing, monitoring, and treating disorders requires advances in biomarker discovery, the subsequent development of accurate signatures that correspond with dynamic disease states, as well as therapeutic interventions that can be continuously optimized and modulated for dose and drug selection. This work highlights key breakthroughs in the development of enabling technologies that further the goal of personalized and precision medicine, and remaining challenges that, when addressed, may forge unprecedented capabilities in realizing truly individualized patient care.

  • Phaeodactylum tricornutum: A Diatom Cell Factory
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-21
    Thomas Butler; Rahul Vijay Kapoore; Seetharaman Vaidyanathan

    A switch from a petroleum-based to a biobased economy requires the capacity to produce both high-value low-volume and low-value high-volume products. Recent evidence supports the development of microalgae-based microbial cell factories with the objective of establishing environmentally sustainable manufacturing solutions. Diatoms display rich diversity and potential in this regard. We focus on Phaeodactylum tricornutum, a pennate diatom that is commonly found in marine ecosystems, and discuss recent trends in developing the diatom chassis for the production of a suite of natural and genetically engineered products. Both upstream and downstream developments are reviewed for the commercial development of P. tricornutum as a cell factory for a spectrum of marketable products.

  • Controlling Voltage Reversal in Microbial Fuel Cells
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-21
    Bongkyu Kim; S. Venkata Mohan; Deby Fapyane; In Seop Chang

    Microbial fuel cell (MFC) systems have been developed for potential use as power sources, along with several other applications, with bacteria as the prime factor enabling electrocatalytic activity. Limited voltage and current production from unit cells limit their practical applicability, so stacking multiple MFCs has been proposed as a way to increase power production. Special attention is paid to voltage reversal (VR), a common occurrence in stacked MFCs, and to identifying the mechanisms underlying this phenomenon. We also proposed realistic perspectives on stacked MFCs in an effort to control and suppress VR by balancing the kinetics in the system, such as using enriched electroactive microorganisms or altering the circuitry mode.

  • Recombineering for Genetic Engineering of Natural Product Biosynthetic Pathways
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-20
    Muhammad Nazeer Abbasi; Jun Fu; Xiaoying Bian; Hailong Wang; Youming Zhang; Aiying Li

    Microbial genomes encode many cryptic and uncharacterized biosynthetic gene clusters (BGCs). Exploiting this unexplored genetic wealth to discover microbial novel natural products (NPs) remains a challenging issue. We review homologous recombination (HR)-based recombineering, mediated by the recombinases RecE/RecT from Rac prophage and Redα/Redβ from lambda phage, which has developed into a highly inclusive tool for direct cloning of large DNA up to 100 kb, seamless mutation, multifragment assembly, and heterologous expression of microbial NP BGCs. Its utilization in the refactoring, engineering, and functional expression of long BGCs for NP biosynthesis makes it easy to elucidate NP-producing potential in microbes. This review also highlights various applications of recombineering in NP-derived drug discovery.

  • Synthetic Rewiring of Plant CO2 Sequestration Galvanizes Plant Biomass Production
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-17
    Muhammad Naseem; Özge Osmanoglu; Thomas Dandekar

    Synthetically designed alternative photorespiratory pathways in tobacco and rice plants have paved the way to enhanced plant biomass production. Likewise, some in vitro- and in vivo-tested carbon-concentrating cycles hold promise to increase plant biomass. We hypothesize a further increase in plant productivity if photorespiratory bypasses are integrated with carbon-concentrating cycles in plants.

  • 3D Printing in Suspension Baths: Keeping the Promises of Bioprinting Afloat
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-16
    Andrew McCormack; Christopher B. Highley; Nicholas R. Leslie; Ferry P.W. Melchels

    Extrusion-based 3D printers have been adopted in pursuit of engineering functional tissues through 3D bioprinting. However, we are still a long way from the promise of fabricating constructs approaching the complexity and function of native tissues. A major challenge is presented by the competing requirements of biomimicry and manufacturability. This opinion article discusses 3D printing in suspension baths as a novel strategy capable of disrupting the current bioprinting landscape. Suspension baths provide a semisolid medium to print into, voiding many of the inherent flaws of printing onto a flat surface in air. We review the state-of-the-art of this approach and extrapolate toward future possibilities that this technology might bring, including the fabrication of vascularized tissue constructs.

  • Gelatin Matrices for Growth Factor Sequestration
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-15
    Taneidra Buie; Joshua McCune; Elizabeth Cosgriff-Hernandez

    Gelatin is used in a broad range of tissue engineering applications because of its bioactivity, mild processing conditions, and ease of modification, which have increased interest in its use as a growth factor delivery vehicle. Traditional methods to control growth factor sequestration and delivery have relied on controlling hydrogel mesh size via chemical crosslinking with corollary changes to the physical properties of the hydrogel. To decouple growth factor release from scaffold properties, affinity sequestration modalities have been developed to preserve the bioactivity of the growth factor through interactions with the modified gelatin. This review provides a summary of these mechanisms, highlights current gelatin growth factor delivery systems, and addresses the future perspective of gelatin matrices for growth factor delivery in tissue engineering.

  • Protein Engineering for Improving and Diversifying Natural Product Biosynthesis
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-15
    Chenyi Li; Ruihua Zhang; Jian Wang; Lauren Marie Wilson; Yajun Yan

    Proteins found in nature have traditionally been the most frequently used biocatalysts to produce numerous natural products ranging from commodity chemicals to pharmaceuticals. Protein engineering has emerged as a powerful biotechnological toolbox in the development of metabolic engineering, particularly for the biosynthesis of natural products. Recently, protein engineering has become a favored method to improve enzymatic activity, increase enzyme stability, and expand product spectra in natural product biosynthesis. This review summarizes recent advances and typical strategies in protein engineering, highlighting the paramount role of protein engineering in improving and diversifying the biosynthesis of natural products. Future prospects and research directions are also discussed.

  • Bacterial Inclusion Bodies: A Treasure Trove of Bioactive Proteins
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-15
    Priyank Singhvi; Ankit Saneja; Sudeepa Srichandan; Amulya K. Panda

    Recombinant proteins expressed as bacterial inclusion bodies (IBs) are now receiving tremendous attention for many diverse applications in the areas of industrial and medical biotechnology. Understanding the structure–function relationship of protein in IBs has recently created new possibilities in developing innovative isolation, solubilization, refolding, and purification processes for high-throughput recovery of bioactive protein from bacterial IBs. This opinion article describes the advantages, disadvantages, and major challenges presently associated with each of the processing steps. Finally, we conclude with the possible solutions for each operational step and the future direction of the basic and translational research to achieve maximum benefit from IB aggregates.

  • The Pathway Less Traveled: Engineering Biosynthesis of Nonstandard Functional Groups
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-15
    Morgan Sulzbach; Aditya M. Kunjapur

    The field of metabolic engineering has achieved biochemical routes for conversion of renewable inputs to structurally diverse chemicals, but these products contain a limited number of chemical functional groups. In this review, we provide an overview of the progression of uncommon or ‘nonstandard’ functional groups from the elucidation of their biosynthetic machinery to the pathway optimization framework of metabolic engineering. We highlight exemplary efforts from primarily the last 5 years for biosynthesis of aldehyde, ester, terminal alkyne, terminal alkene, fluoro, epoxide, nitro, nitroso, nitrile, and hydrazine functional groups. These representative nonstandard functional groups vary in development stage and showcase the pipeline of chemical diversity that could soon appear within customized, biologically produced molecules.

  • Bioengineered 3D Models to Recapitulate Tissue Fibrosis
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-15
    Marta Sacchi; Ruchi Bansal; Jeroen Rouwkema

    Fibrosis, characterized by progressive tissue stiffening resulting in organ failure, is a growing health problem affecting millions of people worldwide. Currently, therapeutic options for tissue fibrosis are severely limited and organ transplantation is the only effective treatment for the end-stage fibrotic diseases with inherent limitations. Recent advancements in engineered 3D in vitro human disease mimic models, recapitulating the tissue pathophysiology, have provided unique state-of-the-art platforms for: (i) understanding the biological mechanisms involved in the disease pathogenesis; and (ii) high-throughput and reproducible drug screening. This review focuses on the recent multidisciplinary developments made towards advanced 3D biomimetic fibrotic tissue (liver, kidney, and lung) models that combine highly precision manufacturing techniques with high cellular functionality and biophysical (mechanical) properties.

  • Stacked Bt Proteins Pose No New Risks to Nontarget Arthropods
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-14
    Jörg Romeis; Michael Meissle

    Concerns have been raised that multiple insecticidal proteins produced by genetically engineered (GE) crops may interact unexpectedly and pose new threats to biodiversity and nontarget organisms. We reviewed the literature to assess whether this concern is justified and whether the current regulatory framework needs to be adapted to address this concern.

  • Bioelectrofuel Synthesis by Nanoenzymes: Novel Alternatives to Conventional Enzymes
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-10
    Lakhveer Singh; Supriyanka Rana; Sveta Thakur; Deepak Pant

    Recent bioinspired efforts of designing novel nanoenzyme-based electrocatalysts are driven by the urgency of making bioelectrofuels more affordable and efficient. Unlike natural enzymes, nanoenzyme-modified electrodes with large surface areas enclose numerous biomimicking active sites to facilitate enhanced microbial growth followed by increased reactant-to-bioelectrofuel conversion.

  • Synthetic Methylotrophy: A Practical Solution for Methanol-Based Biomanufacturing
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-10
    Yu Wang; Liwen Fan; Philibert Tuyishime; Ping Zheng; Jibin Sun

    The increasing availability and affordability of natural gas has renewed interest in using methanol for bioproduction of useful chemicals. Engineering synthetic methylotrophy based on natural or artificial methanol assimilation pathways and genetically tractable platform microorganisms for methanol-based biomanufacturing is drawing particular attention. Recently, intensive efforts have been devoted to demonstrating the feasibility and improving the efficiency of synthetic methylotrophy. Various fuel, bulk, and fine chemicals have been synthesized using methanol as a feedstock. However, fully synthetic methylotrophs utilizing methanol as the sole carbon source and commercially viable bioproduction from methanol remain to be developed. Here, we review ongoing efforts to identify limiting factors, optimize synthetic methylotrophs, and implement methanol-based biomanufacturing. Future challenges and prospects are also discussed.

  • Intravesical Hydrogels as Drug Reservoirs
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-08
    Heping Qiu; Hui Guo; Di Li; Yuchuan Hou; Tairong Kuang; Jianxun Ding

    The complex environment in the bladder weakens the efficacy of intravesical therapy. Hydrogel-based drug delivery systems are poised to revolutionize the delivery of therapeutic agents to bladder lesion sites. This forum article highlights the prospective applications of hydrogels as drug reservoirs in treating chronic bladder diseases.

  • Metabolic Engineering of Escherichia coli for Natural Product Biosynthesis
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-07
    Dongsoo Yang; Seon Young Park; Yae Seul Park; Hyunmin Eun; Sang Yup Lee

    Natural products are widely employed in our daily lives as food additives, pharmaceuticals, nutraceuticals, and cosmetic ingredients, among others. However, their supply has often been limited because of low-yield extraction from natural resources such as plants. To overcome this problem, metabolically engineered Escherichia coli has emerged as a cell factory for natural product biosynthesis because of many advantages including the availability of well-established tools and strategies for metabolic engineering and high cell density culture, in addition to its high growth rate. We review state-of-the-art metabolic engineering strategies for enhanced production of natural products in E. coli, together with representative examples. Future challenges and prospects of natural product biosynthesis by engineered E. coli are also discussed.

  • Ultrafast Photonic PCR Based on Photothermal Nanomaterials
    Trends Biotechnol. (IF 13.747) Pub Date : 2020-01-06
    Minli You; Zedong Li; Shangsheng Feng; Bin Gao; Chunyan Yao; Jie Hu; Feng Xu

    Over the past few decades, PCR has been the gold standard for detecting nucleic acids (NAs) in various biomedical fields. However, there are several limitations associated with conventional PCR, such as complicated operation, need for bulky equipment, and, in particular, long thermocycling time. Emerging nanomaterials with photothermal effects have shown great potential for developing a new generation of PCR: ultrafast photonic PCR. Here, we review recent applications of photothermal nanomaterials in ultrafast photonic PCR. First, we introduce emerging photothermal nanomaterials and their light-to-heat energy conversion process in photonic PCR. We then review different photothermal nanomaterial-based photonic PCRs and compare their merits and drawbacks. Finally, we summarize existing challenges with photonic PCR and hypothesize its promising future research directions.

  • Phosphoprotein Biosensors for Monitoring Pathological Protein Structural Changes
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-12-26
    Mostak Ahmed; Kevin M. Koo; Paul N. Mainwaring; Laura G. Carrascosa; Matt Trau

    Current biotechnological developments are driving a significant shift towards integrating proteomic analysis with landmark genomic, methylomic, and transcriptomic data to elucidate functional effects. For the majority of proteins, structure and function are closely intertwined. Post-translational protein modifications (e.g., phosphorylation) leading to aberrantly active structures can originate a wide variety of pathological conditions, including cancer. Analysis of protein structure variants is thus integral to the identification of clinically actionable targets and the design of novel disease diagnosis and therapy approaches. However, it is still challenging to interrogate subtle structural changes of proteins in a rapid and cost-effective manner with current tools. This review primarily compiles the latest biosensing techniques for protein structural analysis.

  • Natural Medicinal Compounds in Bone Tissue Engineering
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-12-25
    Susmita Bose; Naboneeta Sarkar

    Recent advances in 3D printing have provided unprecedented opportunities in bone tissue engineering applications for producing a variety of complex patient-specific implants for the treatment of critical-sized bone defects. Natural medicinal compounds (NMCs) with osteogenic potential can be incorporated into these 3D-printed parts to improve bone formation and therefore enhance implant performance. Using NMCs to treat bone-related disorders may prove to be a healthy preventive choice as they are considered safe, have lesser or no side effects, and are more suitable for prolonged use than synthetic drugs. In this review paper, the current challenges of bone tissue engineering are addressed briefly, highlighting the immense potential of NMCs integrated within tissue engineering scaffolds for orthopedic and dental applications.

  • Elastin Biomaterials in Dermal Repair
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-12-23
    Qingyun Wen; Suzanne M. Mithieux; Anthony S. Weiss

    Wound healing has historically relied on endogenous processes, but engineered materials are increasingly being used to assist tissue repair. Elastin is an essential functional component of the dermal extracellular matrix and is an important part of skin wound repair that encompasses an elastic dermis. Advances in modern technology have better elucidated the specific signaling factors and cells that contribute to the physiological process and have led to new developments in wound care technology. We review elastin-based materials that are used to encourage wound repair. Elastin-related biomaterials, particularly those based on tropoelastin, are particularly promising because tropoelastin is assembled to make elastin. We present insights into the roles of elastin-related biomaterials and their associated in vitro and in vivo benefits on wound healing.

  • Microdroplet-Assisted Screening of Biomolecule Production for Metabolic Engineering Applications
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-12-10
    Emily K. Bowman, Hal S. Alper

    Success in synthetic biology and metabolic engineering is quickly becoming ‘test’ limited within the design–build–test cycle. Commonly used methods for high-throughput screening, including fluorescence-activated cell sorting (FACS) and microtiter plates, have intracellular product and throughput limitations. A growing alternative to these challenges is the use of microfluidic microdroplet-based methods, which offer the advantages of microtiter plates with the throughput and ease of flow-based approaches. In this review, we examine available microdroplet technologies and their applications from droplet generation to sensing and finally sorting and evaluation for metabolic engineering applications. Additionally, we cover recent microdroplet advances, including the ability to perform mass spectrometry (MS) on individual microdroplets and dispense them into microtiter plates after sorting via fluorescence-activated droplet sorting (FADS).

  • Cancer Immunoimaging with Smart Nanoparticles
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-12-05
    Yu-Chuan Ou, Xiaona Wen, Rizia Bardhan

    Dynamic immunoimaging in vivo is crucial in patient-tailored immunotherapies to identify patients who will benefit from immunotherapies, monitor therapeutic efficacy post treatment, and determine alternative strategies for nonresponders. Nanoparticles have played a major role in the immunotherapy landscape. In this review, we summarize recent findings in immunoimaging where smart nanoparticles target, detect, stimulate, and deliver therapeutic dose in vivo. Nanoparticles interfaced with an immunoimaging toolbox enable the use of multiple modalities and achieve depth-resolved whole-body tracking of immunomarkers with high accuracy both before and after treatment. We highlight how functional nanoparticles track T cells, dendritic cells (DCs), tumor-associated macrophages (TAMs), and immune checkpoint receptors (ICRs), and facilitate image-guided interventions.

  • Next-Generation Sequencing: An Eye-Opener for the Surveillance of Antiviral Resistance in Influenza
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-12-04
    Laura A.E. Van Poelvoorde, Xavier Saelens, Isabelle Thomas, Nancy H. Roosens

    Next-generation sequencing (NGS) can enable a more effective response to a wide range of communicable disease threats, such as influenza, which is one of the leading causes of human morbidity and mortality worldwide. After vaccination, antivirals are the second line of defense against influenza. The use of currently available antivirals can lead to antiviral resistance mutations in the entire influenza genome. Therefore, the methods to detect these mutations should be developed and implemented. In this Opinion, we assess how NGS could be implemented to detect drug resistance mutations in clinical influenza virus isolates.

  • Leveling Up Hydrogels: Hybrid Systems in Tissue Engineering
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-29
    Sara C. Neves, Lorenzo Moroni, Cristina C. Barrias, Pedro L. Granja

    Hydrogels can mimic several features of the cell native microenvironment and have been widely used as synthetic extracellular matrices (ECMs) in tissue engineering and regenerative medicine (TERM). However, some applications have specifications that hydrogels cannot efficiently fulfill on their own. Incorporating reinforcing structures like fibrous scaffolds or particles into hydrogels, as hybrid systems, is a promising strategy to improve their functionality. We describe recent advances in the fabrication and application of these hybrid systems, where structural properties and stimuli responsiveness of hydrogels are enhanced while their ECM-like features are preserved. Furthermore, we discuss how these systems can contribute to the development of more complex tissue engineered structures in the rapidly evolving field of TERM.

  • Unearthing Hidden Chemical Potential from Discarded Actinobacterial Libraries
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-27
    Marshall L. Timmermans, Avena C. Ross

    The redundancy of natural product biosynthesis in microbes poses a practical challenge for discovering new antimicrobial compounds from bacteria. The recent application of clustered regularly interspaced short palindromic repeats (CRISPR) technology by Culp et al. to inactivate the production of abundant antibiotics generates a metabolic clean slate for the detection and/or isolation of new and less plentiful antibiotics activated in mutant strains.

  • Gut Check Time: Antibiotic Delivery Strategies to Reduce Antimicrobial Resistance
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-19
    Stephen A. Kelly, Aoife M. Rodgers, Séamus C. O’Brien, Ryan F. Donnelly, Brendan F. Gilmore

    Antimicrobial resistance (AMR) has developed into a huge threat to global health, and reducing it is an urgent priority for public health authorities. The importance of a healthy and balanced gut microbiome has been identified as a key protective factor against AMR development, but this can be significantly affected by antibiotic therapy, resulting in dysbiosis and reduction of taxonomic richness. The way in which antibiotics are administered could form an important part of future antimicrobial stewardship strategies, where drug delivery is ideally placed to play a key role in the fight against AMR. This review focuses on drug delivery strategies for antibiotic administration, including avoidance of the gut microbiome and targeted delivery approaches, which may reduce AMR.

  • Hands-On Introduction to Synthetic Biology for Security Professionals
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-07-15
    Neil R. Adames, Jenna E. Gallegos, Sonia Y. Hunt, William K. So, Jean Peccoud

    The rapid pace of life sciences innovations and a growing list of nontraditional actors engaging in biological research make it challenging to develop appropriate policies to protect sensitive infrastructures. To address this challenge, we developed a five-day awareness program for security professionals, including laboratory work, site visits, and lectures.

  • Synthetic Biology and the United Nations
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-06-27
    Hung-En Lai, Caoimhe Canavan, Loren Cameron, Simon Moore, Monika Danchenko, Todd Kuiken, Zuzana Sekeyová, Paul S. Freemont

    Synthetic biology is a rapidly emerging interdisciplinary field of science and engineering that aims to redesign living systems through reprogramming genetic information. The field has catalysed global debate among policymakers and publics. Here we describe how synthetic biology relates to these international deliberations, particularly the Convention on Biological Diversity (CBD).

  • Paradigm Shift in Algal H2 Production: Bypassing Competitive Processes
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-06-04
    Szilvia Z. Tóth, Iftach Yacoby

    Hydrogen is a promising energy carrier, but producing it sustainably remains a challenge. Green algae can produce hydrogen photosynthetically using their efficient but oxygen-sensitive hydrogenases. Recent strategies aiming to bypass competing processes provide a promising route for scaling up algal hydrogen production.

  • Antimicrobial Inks: The Anti-Infective Applications of Bioprinted Bacterial Polysaccharides
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-06-03
    Ronan R. McCarthy, Muhammad Wajid Ullah, Eujin Pei, Guang Yang

    Bioprinting is a rapidly emerging technology with the potential to transform the biomedical sector. Here, we discuss how a range of bacterial polysaccharides with antibiofilm and antibacterial activity could be used to augment current bioink formulations to improve their biocompatibility and tackle the spread of antibiotic-resistant infections.

  • A Makerspace for Life Support Systems in Space
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-07-11
    Jessica E. Snyder, David Walsh, Peter A. Carr, Lynn J. Rothschild

    Human space exploration and settlement will require leaps forward in life support for environmental management and healthcare. Life support systems must efficiently use nonrenewable resources packed from Earth while increasingly relying on resources available locally in space. On-demand production of components and materials (e.g., 3D printing and synthetic biology) holds promise to satisfy the evolving set of supplies necessary to outfit human missions to space. We consider here life support systems for missions planned in the 2020s, and discuss how the maker and 'do-it-yourself' (DIY) biology communities can develop rapid, on-demand manufacturing techniques and platforms to address these needs. This Opinion invites the diverse maker community into building the next generation of flight hardware for near-term space exploration.

  • Wearable Devices for Single-Cell Sensing and Transfection
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-05-06
    Lingqian Chang, Yu-Chieh Wang, Faheem Ershad, Ruiguo Yang, Cunjiang Yu, Yubo Fan

    Wearable healthcare devices are mainly used for biosensing and transdermal delivery. Recent advances in wearable biosensors allow for long-term and real-time monitoring of physiological conditions at a cellular resolution. Transdermal drug delivery systems have been further scaled down, enabling wide selections of cargo, from natural molecules (e.g., insulin and glucose) to bioengineered molecules (e.g., nanoparticles). Some emerging nanopatches show promise for precise single-cell gene transfection in vivo and have advantages over conventional tools in terms of delivery efficiency, safety, and controllability of delivered dose. In this review, we discuss recent technical advances in wearable micro/nano devices with unique capabilities or potential for single-cell biosensing and transfection in the skin or other organs, and suggest future directions for these fields.

  • Microchannels in Development, Survival, and Vascularisation of Tissue Analogues for Regenerative Medicine
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-05-07
    Khoon S. Lim, Marissa Baptista, Shahana Moon, Tim B.F. Woodfield, Jelena Rnjak-Kovacina

    Microchannels are simple, perfusable architectural features engineered into biomaterials to promote mass transport of solutes to cells, effective cell seeding and compartmentalisation for tissue engineering applications, control over spatiotemporal distribution of molecules and ligands, and survival, integration, and vascularisation of engineered tissue analogues in vivo. Advances in biofabrication have led to better control over microchannel fabrication in 3D scaffolds, enabling sophisticated designs that drive the development of complex tissue structures. This review addresses the importance of microchannel structures in biomaterial design and regenerative medicine, and discusses their function, fabrication methods, and proposed mechanisms underlying their effects.

  • Accelerating Climate Resilient Plant Breeding by Applying Next-Generation Artificial Intelligence
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-06-21
    Antoine L. Harfouche, Daniel A. Jacobson, David Kainer, Jonathon C. Romero, Antoine H. Harfouche, Giuseppe Scarascia Mugnozza, Menachem Moshelion, Gerald A. Tuskan, Joost J.B. Keurentjes, Arie Altman

    Breeding crops for high yield and superior adaptability to new and variable climates is imperative to ensure continued food security, biomass production, and ecosystem services. Advances in genomics and phenomics are delivering insights into the complex biological mechanisms that underlie plant functions in response to environmental perturbations. However, linking genotype to phenotype remains a huge challenge and is hampering the optimal application of high-throughput genomics and phenomics to advanced breeding. Critical to success is the need to assimilate large amounts of data into biologically meaningful interpretations. Here, we present the current state of genomics and field phenomics, explore emerging approaches and challenges for multiomics big data integration by means of next-generation (Next-Gen) artificial intelligence (AI), and propose a workable path to improvement.

  • Production and Biomedical Application of Flavivirus-like Particles
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-04-16
    Ewelina Krol, Gabriela Brzuska, Boguslaw Szewczyk

    Many viruses belonging to the Flaviviridae family are transmitted by invertebrate vectors. Among those transmitted by mosquitos, there are many human pathogens of great medical importance, such as Japanese encephalitis virus, West Nile virus, dengue virus, Zika virus, or yellow fever virus. Millions of people contract mosquito-borne diseases each year, leading to thousands of deaths. Co-circulation of genetically similar flaviviruses in the same areas result in the generation of crossreactive antibodies, which is of serious concern for the development of effective vaccines and diagnostic tests. This review provides comprehensive insight into the potential use of virus-like particles as safe and effective antigens in both diagnostics tests, as well as in the development of vaccines against several mosquito-borne flaviviruses.

  • New Prospects for Modified Algae in Heavy Metal Adsorption
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-06-04
    Sze Yin Cheng, Pau-Loke Show, Beng Fye Lau, Jo-Shu Chang, Tau Chuan Ling

    Heavy metal pollution is one of the most pervasive environmental problems globally. Novel finely tuned algae have been proposed as a means to improve the efficacy and selectivity of heavy metal biosorption. This article reviews current research on selective algal heavy metal adsorption and critically discusses the performance of novel biosorbents. We emphasize emerging state-of-the-art techniques that customize algae for enhanced performance and selectivity, particularly molecular and chemical extraction techniques as well as nanoparticle (NP) synthesis approaches. The mechanisms and processes for developing novel algal biosorbents are also presented. Finally, we discuss the applications, challenges, and future prospects for modified algae in heavy metal biosorption.

  • Recent Advances in Biosensors for Detecting Cancer-Derived Exosomes
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-05-16
    Nan Cheng, Dan Du, Xinxian Wang, Dong Liu, Wentao Xu, Yunbo Luo, Yuehe Lin

    Early detection and effective treatments are two of the greatest challenges in the fight against cancer. Cancer-derived exosomes are attractive biomarkers for the early diagnosis and therapeutic response evaluation of cancer. Here, we review recent advances in biosensors for the detection of cancer-derived exosomes. We discuss the potential exosomal biomarkers of various cancers, which can be applied as indicative targets in the design of biosensors. We further describe the fabrication of exosome detection biosensors with respect to biological recognition strategies and signal transduction techniques, which involve integrated scientific and technological aspects of analytical chemistry and nanotechnology. Furthermore, future research directions and challenges in using cancer-derived exosomes for point-of-care (POC) testing are presented.

  • The Microbiome: A Life Science Opportunity for Our Society and Our Planet
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-07-22
    Aleksandra Małyska, Marios Nektarios Markakis, Carina F. Pereira, Marc Cornelissen

    Microbiome research and innovation (R&I) promises solutions to a broad range of business and societal challenges. To bridge the gap between today’s potential and the moment at which concrete applications start generating societal impact, critical-scale efforts offering visible progress on topics of public interest will be essential.

  • Integrating Organs-on-Chips: Multiplexing, Scaling, Vascularization, and Innervation
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-07-22
    DoYeun Park, Jaeseo Lee, Justin J. Chung, Youngmee Jung, Soo Hyun Kim

    Organs-on-chips (OoCs) have attracted significant attention because they can be designed to mimic in vivo environments. Beyond constructing a single OoC, recent efforts have tried to integrate multiple OoCs to broaden potential applications such as disease modeling and drug discoveries. However, various challenges remain for integrating OoCs towards in vivo-like operation, such as incorporating various connections for integrating multiple OoCs. We review multiplexed OoCs and challenges they face: scaling, vascularization, and innervation. In our opinion, future OoCs will be constructed to have increased predictive power for in vivo phenomena and will ultimately become a mainstream tool for high quality biomedical and pharmaceutical research.

  • Production and Quality Requirements of Human Platelet Lysate: A Position Statement from the Working Party on Cellular Therapies of the International Society of Blood Transfusion
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-07-17
    Katharina Schallmoser, Reinhard Henschler, Christian Gabriel, Mickey B.C. Koh, Thierry Burnouf

    Human platelet lysate (HPL), rich in growth factors, is an efficient alternative supplement to fetal bovine serum (FBS) for ex vivo propagation of stromal cell-based medicinal products. Since 2014, HPL has been a focus of the Working Party for Cellular Therapies of the International Society of Blood Transfusion (ISBT). Currently, as several Good Manufacturing Practice (GMP)-compliant manufacturing protocols exist, an international consensus defining the optimal modes of industrial production, product specification, pathogen safety, and release criteria of this ancillary material (AM) is needed. This opinion article by the ISBT Working Party summarizes the current knowledge on HPL production and proposes recommendations on manufacturing and quality management in line with current technological innovations and regulations of biological products and advanced therapy medicinal products.

  • The Regulation of Wearable Medical Devices
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-07-15
    Nan Jiang, Julia E. Mück, Ali K. Yetisen

    This article provides a guideline for the design, manufacture, regulatory approval, and post-market surveillance (PMS) of wearable medical devices (WMDs). The integration of regulatory considerations can accelerate wearable device (WD) development from laboratory to market while mitigating device failure risks. The implementation of stringent clinical evaluations will transcend WDs beyond consumer products.

  • A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-07-15
    Isabel Calejo, Raquel Costa-Almeida, Rui L. Reis, Manuela E. Gomes

    Musculoskeletal diseases are increasing the prevalence of physical disability worldwide. Within the body, musculoskeletal soft and hard tissues integrate through specific multitissue transitions, allowing for body movements. Owing to their unique compositional and structural gradients, injuries challenge the native interfaces and tissue regeneration is unlikely to occur. Tissue engineering strategies are emerging to emulate the physiological environment of soft-to-hard tissue interfaces. Advances in biomaterial design enable control over biophysical parameters, but biomaterials alone are not sufficient to provide adequate support and guide transplanted cells. Therefore, biological, biophysical, and biochemical tools can be integrated into a multifactorial toolbox, steering prospective advances toward engineering clinically relevant soft-to-hard tissue interfaces.

  • Will Following the Regulatory Script for GMOs Promote Public Acceptance of Gene-Edited Crops?
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-07-13
    Rod A. Herman, Maria Fedorova, Nicholas P. Storer

    Risk-disproportionate regulation of gene-edited crops has been proposed to gain public acceptance for this breeding technique. However, confounding safety regulations with advocacy for an underlying technology risks weakening achievement of both objectives. Dedicated factual communication and education from trusted sources is likely to better support public acceptance of gene-edited crops.

  • New Horizons in Acetogenic Conversion of One-Carbon Substrates and Biological Hydrogen Storage
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-06-27
    Volker Müller

    Strictly anaerobic, acetogenic (acetate-forming) bacteria are characterized by a reductive pathway in which two mol of CO2 are reduced to one mol of acetyl coenzyme A (acetyl-CoA) and then further to acetate, ethanol, or butyrate. Therefore, they have come into focus for an alternative, CO2-based bioeconomy. Other one-carbon (C1) substrates, such as formic acid or methanol, are promising feedstocks for an alternative bioeconomy using acetogens as biocatalysts that have been somewhat overlooked. In addition, acetogens, such as Acetobacterium woodii and Thermoanaerobacter kivui, have a unique enzyme system capable of reducing CO2 to formate with H2 as reductant that is superior over any chemical catalyst for CO2-based hydrogen storage. Therefore, acetogens are also promising candidates in the hydrogen economy as potential catalysts for hydrogen storage or production.

  • Optogenetics in the Era of Cerebral Organoids
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-06-18
    Zahra Shiri, Susan Simorgh, Somayeh Naderi, Hossein Baharvand

    The human brain has been deemed the most complex organ and has captivated neuroscientists for decades. Most studies of this organ have relied on reductionist model systems. Although all model systems are essentially wrong, cerebral organoids so far represent the closest recapitulation of human brain development and disease both in terms of cell diversity and organization. The optogenetic technique can be used in this context to study the functional neuroanatomy of the brain, to examine the neural circuits, and to determine the etiology of neurological disorders. In this opinion article, we suggest ways in which optogenetics can be combined with cerebral organoids to allow unprecedented precision and accuracy in studying normal and aberrant neurodevelopmental processes and, as well, neurodegenerative diseases.

  • New Frontiers for Biofabrication and Bioreactor Design in Microphysiological System Development
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-06-12
    Jonathon Parrish, Khoon Lim, Boyang Zhang, Milica Radisic, Tim B.F. Woodfield

    Microphysiological systems (MPSs) have been proposed as an improved tool to recreate the complex biological features of the native niche with the goal of improving in vitro–in vivo extrapolation. In just over a decade, MPS technologies have progressed from single-tissue chips to multitissue plates with integrated pumps for perfusion. Concurrently, techniques for biofabrication of complex 3D constructs for regenerative medicine and 3D in vitro models have evolved into a diverse toolbox for micrometer-scale deposition of cells and cell-laden bioinks. However, as the complexity of biological models increases, experimental throughput is often compromised. This review discusses the existing disparity between MPS complexity and throughput, then examines an MPS-terminated biofabrication line to identify the hurdles and potential approaches to overcoming this disparity.

  • Designing Biobased Recyclable Polymers for Plastics
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-05-28
    Rajni Hatti-Kaul, Lars J. Nilsson, Baozhong Zhang, Nicola Rehnberg, Stefan Lundmark

    Several concurrent developments are shaping the future of plastics. A transition to a sustainable plastics system requires not only a shift to fossil-free feedstock and energy to produce the carbon-neutral building blocks for polymers used in plastics, but also a rational design of the polymers with both desired material properties for functionality and features facilitating their recyclability. Biotechnology has an important role in producing polymer building blocks from renewable feedstocks, and also shows potential for recycling of polymers. Here, we present strategies for improving the performance and recyclability of the polymers, for enhancing degradability to monomers, and for improving chemical recyclability by designing polymers with different chemical functionalities.

  • Advances in Microfluidic Blood–Brain Barrier (BBB) Models
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-05-23
    Arianna Oddo, Bo Peng, Ziqiu Tong, Yingkai Wei, Wing Yin Tong, Helmut Thissen, Nicolas Hans Voelcker

    Therapeutic options for neurological disorders currently remain limited. The intrinsic complexity of the brain architecture prevents potential therapeutics from reaching their cerebral target, thus limiting their efficacy. Recent advances in microfluidic technology and organ-on-chip systems have enabled the development of a new generation of in vitro platforms that can recapitulate complex in vivo microenvironments and physiological responses. In this context, microfluidic-based in vitro models of the blood–brain barrier (BBB) are of particular interest as they provide an innovative approach for conducting research related to the brain, including modeling of neurodegenerative diseases and high-throughput drug screening. Here, we present the most recent advances in BBB-on-chip devices and examine validation steps that will strengthen their future applications.

  • Synthetic Biology and Genome-Editing Tools for Improving PHA Metabolic Engineering
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-11
    Xu Zhang, Yina Lin, Qiong Wu, Ying Wang, Guo-Qiang Chen

    Polyhydroxyalkanoates (PHAs) are a diverse family of biopolyesters synthesized by many natural or engineered bacteria. Synthetic biology and DNA-editing approaches have been adopted to engineer cells for more efficient PHA production. Recent advances in synthetic biology applied to improve PHA biosynthesis include ribosome-binding site (RBS) optimization, promoter engineering, chromosomal integration, cell morphology engineering, cell growth behavior reprograming, and downstream processing. More importantly, the genome-editing tool clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has been applied to optimize the PHA synthetic pathway, regulate PHA synthesis-related metabolic flux, and control cell shapes in model organisms, such as Escherichia coli, and non-model organisms, such as Halomonas. These synthetic biology methods and genome-editing tools contribute to controllable PHA molecular weights and compositions, enhanced PHA accumulation, and easy downstream processing.

  • Synthetic Biology Category Wins the 350th Anniversary Merck Innovation Cup
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-09
    Ângelo P. Matos, Amy Kauffman, Christopher Vickery, Kaleb Naegeli, Lisa Strittmatter, Anastasiya Sybirna, Janneke van Blijswijk, Lorenz Adlung, Tetyana Berbasova, Jhon Enterina, Lena Eismann, Braden Tierney, Josua Jordi, Lian Zhu, Sebald Verkuijl, Lorillee Tallorin, Arne Wehling, Michael Ogden, Ulrich A.K. Betz

    Over the past 350 years, Merck has developed science and technology especially in health care, life sciences, and performance materials. To celebrate so many productive years, Merck conducted a special expanded anniversary edition of the Innovation Cup in combination with the scientific conference Curious2018 – Future Insight in Darmstadt, Germany.

  • Synthetic Protein Scaffolding at Biological Membranes
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-09
    James B.Y.H. Behrendorff, Guillem Borràs-Gas, Mathias Pribil

    Protein scaffolding is a natural phenomenon whereby proteins colocalize into macromolecular complexes via specific protein–protein interactions. In the case of metabolic enzymes, protein scaffolding drives metabolic flux through specific pathways by colocalizing enzyme active sites. Synthetic protein scaffolding is increasingly used as a mechanism to improve product specificity and yields in metabolic engineering projects. To date, synthetic scaffolding has focused primarily on soluble enzyme systems, but many metabolic pathways for high-value secondary metabolites depend on membrane-bound enzymes. The compositional diversity of biological membranes and general challenges associated with modifying membrane proteins complicate scaffolding with membrane-requiring enzymes. Several recent studies have introduced new approaches to protein scaffolding at membrane surfaces, with notable success in improving product yields from specific metabolic pathways.

  • Biotechnological Advances in the Design of Algae-Based Biosensors
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-07
    Amina Antonacci, Viviana Scognamiglio

    In addition to their use in biomass production and bioremediation, algae have been extensively exploited in biosensing applications. Algae-based biosensors have demonstrated potential for sensitive, sustainable, and multiplexed detection of analytes of agroenvironmental and security interest. Their advantages include the availability of different algal bioreceptors including whole cells and their photosynthetic subcomponents, their potential to be integrated into dual transduction miniaturized devices, and the opportunity for continuous environmental monitoring. Despite obstacles including limited stability and selectivity, algae-based biosensing is a realistic prospect that has some recent effective applications. Strategic exploitation of cutting-edge technologies including materials science, nanotechnology, microfluidics, and genome editing will help to achieve the full potential of algae-based sensors.

  • Injectable Cryogels for Biomedical Applications
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-05
    Loek J. Eggermont, Zachary J. Rogers, Thibault Colombani, Adnan Memic, Sidi A. Bencherif

    To prevent postoperative complications, there has been a substantial interest in designing syringe-injectable hydrogels. To date, cryogels remain the only viable option for preformed and large-scale hydrogels to be delivered through a conventional needle–syringe injection. Cryogels, a type of hydrogel with exceptional features, are fabricated at subzero temperatures. This process typically results in a biomaterial with a unique macroporous network, shape-memory properties, and exceptional flexibility allowing syringe injectability. These advanced biomaterials have been used for a number of biomedical applications, including tissue engineering, drug delivery, and more recently, immunotherapy. This review summarizes the recent progress on the design of injectable cryogels, their current limitations, and strategies to further improve their properties for translatability into the clinic.

  • Strand Displacement Strategies for Biosensor Applications
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-01
    Yifan Dai, Ariel Furst, Chung Chiun Liu

    DNA has many unique properties beyond encoding genetic information, one of which is its physicochemical stability based on Watson–Crick base pairing. Differences in sequence complementarity between multiple DNA strands can lead to the strand displacement reaction (SDR). SDRs have been regularly applied in synthetic biology, drug delivery, and, importantly, biosensing. SDR-based biosensors have high controllability, high sensitivity, and low interference, and can be used for multiplexed detection. Such biosensors have been demonstrated to detect nearly every class of biomolecule. As the field continues to mature, such platforms can be used as an integral tool for the manipulation of biomolecular reactions, bringing biosensors one step closer to the ultimate goal of point-of-care systems.

  • Industrial Enzymology: The Next Chapter
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-01
    Michael V. Arbige, Jay K. Shetty, Gopal K. Chotani

    This review focuses on recent developments in industrial enzymology, protein engineering, and the design and production of microorganisms. We highlight the latest recombinant DNA (rDNA) technology and tools of protein engineering. These advancements are delivering solutions that address the large unmet needs of customers and markets. To illustrate the progress made over the past three decades, several technological developments and applications are highlighted. High-throughput methods of cell and protein engineering have increased the pace of commercialization. Continuous innovations have impacted many areas of industrial biotechnology and its applications; for example, laundry and dish washing, textile processing, animal health, and human nutrition. The worldwide growth of this bioindustry reflects the potential of biotechnology, which in turn adds a new chapter to the field of industrial enzymology.

  • Contemporary Tools for Regulating Gene Expression in Bacteria
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-11-01
    Ross Kent, Neil Dixon

    Insights from novel mechanistic paradigms in gene expression control have led to the development of new gene expression systems for bioproduction, control, and sensing applications. Coupled with a greater understanding of synthetic burden and modern creative biodesign approaches, contemporary bacterial gene expression tools and systems are emerging that permit fine-tuning of expression, enabling greater predictability and maximisation of specific productivity, while minimising deleterious effects upon cell viability. These advances have been achieved by using a plethora of regulatory tools, operating at all levels of the so-called ‘central dogma’ of molecular biology. In this review, we discuss these gene regulation tools in the context of their design, prototyping, integration into expression systems, and biotechnological application.

  • Molecularly Imprinted Polymers for Cell Recognition
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-10-31
    Stanislav Piletsky, Francesco Canfarotta, Alessandro Poma, Alessandra Maria Bossi, Sergey Piletsky

    Since their conception 50 years ago, molecularly imprinted polymers (MIPs) have seen extensive development both in terms of synthetic routes and applications. Cells are perhaps the most challenging target for molecular imprinting. Although early work was based almost entirely around microprinting methods, recent developments have shifted towards epitope imprinting to generate MIP nanoparticles (NPs). Simultaneously, the development of techniques such as solid phase MIP synthesis has solved many historic issues of MIP production. This review briefly describes various approaches used in cell imprinting with a focus on applications of the created materials in imaging, drug delivery, diagnostics, and tissue engineering.

  • In-Hospital Production of Medicines: Preparing for Disruption
    Trends Biotechnol. (IF 13.747) Pub Date : 2019-10-31
    Shona Kalkman, Marlous Arentshorst, Jarno Hoekman, Wouter Boon, Esther Uijtendaal, Ghislaine van Thiel, Ellen Moors

    In-hospital production of affordable medicines holds potential to address problems of drug accessibility. However, expanding the scope of magistral preparation to include high-cost drugs and complex biologicals gives rise to new challenges. We discuss ethical and regulatory complexities faced by Dutch initiatives defying the current pharmaceutical system through magistral preparation.

Contents have been reproduced by permission of the publishers.
上海纽约大学William Glover