Bio-smart hydrogels: co-joined molecular recognition and signal transduction in biosensor fabrication and drug delivery

Two classes of polymers that are currently receiving widespread attention in biosensor development are hydrogels and conducting electroactive polymers. The present study reports on the integration of these two materials to produce electroactive hydrogel composites that physically entrap enzymes within their matrices for biosensor construction and chemically stimulated controlled release. Enhanced biosensing capabilities of these membranes have been demonstrated in the fabrication of glucose, cholesterol and galactose amperometric biosensors. All biosensors displayed extended linear response ranges (10(-5)-10(-2) M), rapid response times (<60 s), retained storage stabilities of up to 1 year, and excellent screening of the physiological interferents ascorbic acid, uric acid, and acetaminophen. When the cross-linked hydrogel components of these composite membranes were prepared with the amine containing dimethylaminoethyl methacrylate monomer the result was polymeric devices that swelled in response to pH changes (neutral to acidic). Entrapment of glucose oxidase within these materials made them glucose-responsive through the formation of gluconic acid. When insulin was co-loaded with glucose oxidase into these "bio-smart" devices, there was a twofold increase in insulin release rate when the devices were immersed in glucose solutions. This demonstrates the potential of such systems to function as a chemically-synthesized artificial pancreas.     

Electroactive polymer actuators as artificial muscles: are they ready for bioinspired applications?

Electroactive polymer (EAP) actuators are electrically responsive materials that have several characteristics in common with natural muscles. Thus, they are being studied as 'artificial muscles' for a variety of biomimetic motion applications. EAP materials are commonly classified into two major families: ionic EAPs, activated by an electrically induced transport of ions and/or solvent, and electronic EAPs, activated by electrostatic forces. Although several EAP materials and their properties have been known for many decades, they have found very limited applications. Such a trend has changed recently as a result of an effective synergy of at least three main factors: key scientific breakthroughs being achieved in some of the existing EAP technologies; unprecedented electromechanical properties being discovered in materials previously developed for different purposes; and higher concentration of efforts for industrial exploitation. As an outcome, after several years of basic research, today the EAP field is just starting to undergo transition from academia into commercialization, with significant investments from large companies. This paper presents a brief overview on the full range of EAP actuator types and the most significant areas of interest for applications. It is hoped that this overview can instruct the reader on how EAPs can enable bioinspired motion systems.     

Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering

New generations of synthetic biomaterials are being developed at a rapid pace for use as three-dimensional extracellular microenvironments to mimic the regulatory characteristics of natural extracellular matrices (ECMs) and ECM-bound growth factors, both for therapeutic applications and basic biological studies. Recent advances include nanofibrillar networks formed by self-assembly of small building blocks, artificial ECM networks from protein polymers or peptide-conjugated synthetic polymers that present bioactive ligands and respond to cell-secreted signals to enable proteolytic remodeling. These materials have already found application in differentiating stem cells into neurons, repairing bone and inducing angiogenesis. Although modern synthetic biomaterials represent oversimplified mimics of natural ECMs lacking the essential natural temporal and spatial complexity, a growing symbiosis of materials engineering and cell biology may ultimately result in synthetic materials that contain the necessary signals to recapitulate developmental processes in tissue- and organ-specific differentiation and morphogenesis.     

人工电活性微生物菌群的设计与应用

包括产电菌群和噬电菌群的人工电活性微生物菌群(synthetic electroactive microbial consortia)通过菌种间的物质能量级联反应介导化学能与(光)电能间的相互转化，其可利用底物来源广泛、双向电子传递速率快、环境稳定性强，在清洁电能开发、废水处理、环境修复、生物固碳固氮以及生物燃料、无机纳米材料、高聚物等高值化学品合成等多个领域具有广泛的应用前景。针对人工电活性微生物菌群设计、构建与应用，本文总结电活性微生物菌群界面电子传递和种间电子传递机制，概括基于“劳力分工”原理设计构建人工电活性微生物菌群物质能量级联反应基本架构，总结菌群关系与菌群生态位优化等人工电活性微生物菌群工程化策略，分类列举人工电活性微生物菌群在利用廉价生物质产电、生物光伏固碳产电，光驱噬电生物菌群固氮等相关应用。最后对人工电活性微生物菌群未来研究方向进行了展望。     

Functionalized synthetic biodegradable polymer scaffolds for tissue engineering

Scaffolds (artificial ECMs) play a pivotal role in the process of regenerating tissues in 3D. Biodegradable synthetic polymers are the most widely used scaffolding materials. However, synthetic polymers usually lack the biological cues found in the natural extracellular matrix. Significant efforts have been made to synthesize biodegradable polymers with functional groups that are used to couple bioactive agents. Presenting bioactive agents on scaffolding surfaces is the most efficient way to elicit desired cell/material interactions. This paper reviews recent advancements in the development of functionalized biodegradable polymer scaffolds for tissue engineering, emphasizing the syntheses of functional biodegradable polymers, and surface modification of polymeric scaffolds.     

Oligonucleotide analysis by anion exchange HPLC.

The ability to resolve and purify synthetic oligonucleotides by high performance anion exchange chromatography was evaluated using two wide pore polymeric HPLC matrices. The materials used are rigid macroporous copolymers which have a fully quaternised polyethyleneimine coating to provide a strong anion exchange, quaternary amine, functionality. Oligomers of poly(rA), poly(rC) and RNA produced by alkaline hydrolysis of the polymers were chromatographed to evaluate the selectivity of the system prior to the analysis of synthetic oligonucleotides produced using a commercial oligonucleotide synthesizer.     

Engineering biodegradable and multifunctional peptide-based polymers for gene delivery

The complex nature of in vivo gene transfer establishes the need for multifunctional delivery vectors capable of meeting these challenges. An additional consideration for clinical translation of synthetic delivery formulations is reproducibility and scale-up of materials. In this review, we summarize our work over the last five years in developing a modular approach for synthesizing peptide-based polymers. In these materials, bioactive peptides that address various barriers to gene delivery are copolymerized with a hydrophilic backbone of N-(2-hydroxypropyl)methacrylamide (HPMA) using reversible-addition fragmentation chain-transfer (RAFT) polymerization. We demonstrate that this synthetic approach results in well-defined, narrowly-disperse polymers with controllable composition and molecular weight. To date, we have investigated the effectiveness of various bioactive peptides for DNA condensation, endosomal escape, cell targeting, and degradability on gene transfer, as well as the impact of multivalency and polymer architecture on peptide bioactivity.     

Transducers,sensors, and instrumentation in clinical biomechanics

Successful measurements in any field are dependent on the availability of appropriate transducer materials and the associated instrumentation. In recent years there has been a most welcome advance in both these areas. If we consider first the transducer developments that have recently taken place, these have much to do with the discovery and application of new materials such as electroactive polymers, fibre optic devices and many others. Instrumentation has largely benefitted from the microelectronics revolution. Our ability to process and ultimately display data has improved to a remarkable extent. Indeed, the designer of instrumentation is under enormous pressure to convert the data into the digital domain as early as possible simply because the resulting instrument will usually be easier to design and construct, more accurate, more reliable, smaller and possibly more important still, cheaper. This paper reviews some of these developments, gives a number of examples of applications in the clinical biomechanics area and makes some predictions for future developments.     

基于电活性微生物的芳香烃类污染物转化机制研究进展

芳香烃类化合物(aromatic hydrocarbon compounds)是一类基于苯环结构的有机物,广泛分布在自然环境中,难以自然降解、易被生物积累,且有很大的环境危害性。生物法是有机化合物转化降解的主流工艺,而电活性微生物(electroactive microorganisms, EAM)因其独特的胞外电子传递(extracellular electron transfer, EET)能力和生理代谢模式在芳香烃类化合物污染修复领域具有巨大的应用潜力。电活性微生物可以通过还原脱卤、脱硝与氧化开环过程相结合的方式,最终实现芳香烃类污染物的降解矿化。本文重点综述了电活性微生物降解芳香烃类污染物过程中主要还原/氧化反应机理,归纳了电活性微生物高效还原脱卤、脱硝的关键酶活、代谢途径及转化机理,分析了不同含氧条件下电活性微生物开环方式及降解代谢途径,并通过调控微生物胞外聚合物与添加导电材料等途径来提升电活性微生物的胞外电子传递过程,总结了电极电位、电极材料、电解液性质及温度等环境因子对芳香烃类化合物降解的影响,探讨了芳香烃类污染物的强化生物降解策略的可行性。最后,展望了电活性微生物降解技...     

Projecting contact matrices in 177 geographical regions: An update and comparison with empirical data for the COVID-19 era

Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices show qualitative similarities to the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.     

Affinity chromatography using enzymatically synthesized nucleotide-containing DNA binding polymers

A series of nucleotide-containing polyphenols has been synthesized by a simple, two-step enzymatic method. The binding properties of these synthetic polymers to complementary oligonucleotides have been evaluated using a commercially available oligo(dT)cellulose column. Complementary synthetic nucleosides were retained on this column to a greater extent than non-complementary synthetic nucleosides. These results suggest that the synthetic nucleosides prepared via this two-step enzymatic approach may have application as affinity matrices.     

Current and novel polymeric biomaterials for neural tissue engineering

The nervous system is a crucial component of the body and damages to this system, either by of injury or disease, can result in serious or potentially lethal consequences. Restoring the damaged nervous system is a great challenge due to the complex physiology system and limited regenerative capacity.Polymers, either synthetic or natural in origin, have been extensively evaluated as a solution for restoring functions in damaged neural tissues. Polymers offer a wide range of versatility, in particular regarding shape and mechanical characteristics, and their biocompatibility is unmatched by other biomaterials, such as metals and ceramics. Several studies have shown that polymers can be shaped into suitable support structures, including nerve conduits, scaffolds, and electrospun matrices, capable of improving the regeneration of damaged neural tissues. In general, natural polymers offer the advantage of better biocompatibility and bioactivity, while synthetic or non-natural polymers have better mechanical properties and structural stability. Often, combinations of the two allow for the development of polymeric conduits able to mimic the native physiological environment of healthy neural tissues and, consequently, regulate cell behaviour and support the regeneration of injured nervous tissues.Currently, most of neural tissue engineering applications are in pre-clinical study, in particular for use in the central nervous system, however collagen polymer conduits aimed at regeneration of peripheral nerves have already been successfully tested in clinical trials.This review highlights different types of natural and synthetic polymers used in neural tissue engineering and their advantages and disadvantages for neural regeneration.     

The study of the surface layer of 3D-matrices for tissue engineering

Matrices fabricated by electrospinning from polycaprolactone solutions with human albumin or gelatin to 1,1,1,3,3,3-hexafluoroisopropanol have been investigated. Microstructure of matriх surface was analyzed using scanning electron microscopy. Protein distribution in the surface layer was studied by modification with N-(2-hydroxyethyl)phenazine and X-ray photoelectron spectroscopy. The protein concentration in the surface layer of matrices was up to 12 times higher than in the initial solution, and the lower the protein concentration in the solution, the higher the relative protein content is on the surface of matrices. During incubation of matrices in aqueous solutions protein concentration in the surface layer decreased by less than 10% during the first 30–60 min and remained at this level for a long time (seven days). Treatment with proteinase K resulted in about one-third decrease in protein concentration in the surface layer. Thus, both methods used in this study are applicable for analysis of the surface layer of materials fabricated by electrospinning from mixtures of synthetic and natural polymers; however, X-ray photoelectron spectroscopy appears to be a more informative and convenient method.     

Synthetic biocompatible cyclodextrin-based constructs for local gene delivery to improve cutaneous wound healing

The localized, sustained delivery of growth factors for wound healing therapy is actively being explored by gene transfer to the wound site. Biocompatible matrices such as bovine collagen have demonstrated usefulness in sustaining gene therapy vectors that express growth factors in local sites for tissue repair. Here, new synthetic biocompatible materials are prepared and shown to deliver a protein to cultured cells via the use of an adenoviral delivery vector. The synthetic construct consists of a linear, beta-cyclodextrin-containing polymer and an adamantane-based cross-linking polymer. When the two polymers are combined, they create an extended network by the formation of inclusion complexes between the cyclodextrins and adamantanes. The properties of the network are altered by controlling the polymer molecular weights and the number of adamantanes on the cross-linking polymer, and these modifications and others such as replacement of the beta-cyclodextrin (host) and adamantane (guest) with other cyclodextrins (hosts such as alpha, gamma, and substituted members) and inclusion complex forming molecules (guests) provide the ability to rationally design network characteristics. Fibroblasts exposed to these synthetic constructs show proliferation rates and migration patterns similar to those obtained with collagen. Gene delivery (green fluorescent protein) to fibroblasts via the inclusion of adenoviral vectors in the synthetic construct is equivalent to levels observed with collagen. These in vitro results suggest that the synthetic constructs are suitable for in vivo tissue repair applications.     

合成生物学方法构建电活性大肠杆菌

电活性微生物具有独特的在细胞内外环境之间传递电子的能力。在对天然电活性微生物电子传递机制充分研究的基础上,通过合成生物学方法异源构建天然电活性微生物电子传递结构基础也可以将遗传背景清晰的非电活性大肠杆菌改造为电活性微生物。构建获得的工程化电活性大肠杆菌可以直接应用于微生物燃料电池和生物传感器等领域,同时也可以作为底盘细胞整合相应的目标产物合成通路实现电能驱动的生物合成。本文以合成生物学方法构建电活性大肠杆菌为主题,详细阐述天然电活性微生物电子传递的机理及结构基础,总结了工程化电活性大肠杆菌的构建策略、成功案例以及应用领域,并对合成生物学方法构建电活性大肠杆菌未来的研究方向进行了展望。     

Synthetic polymers functionalized by carbohydrates: a review

Polymers based on carbohydrates have re-emerged as exciting topics of polymer research, due to a worldwide focus on sustainable materials. However, multi-step synthesis of these polymers have made their use as commodity plastics uneconomical, and currently their applications are restricted to biomedical fields. Functionalization of polymers has emerged as another important area of polymer science and technology. Chemically linking sugar moeities onto synthetic polymers is a unique method of functionalization of synthetic polymers, whereby not only is the polymer functionalized, but it can also get other desirable properties such as biodegradability—a property much debated and researched in modern times. This paper reviews several methods of anchoring carbohydrates onto polymers and the advantages and the disadvantages associated with each method, their current and potential applications, and their characterization methods.     

Genetic engineering of structural protein polymers.

Genetic and protein engineering are components of a new polymer chemistry that provide the tools for producing macromolecular polyamide copolymers of diversity and precision far beyond the current capabilities of synthetic polymer chemistry. The genetic machinery allows molecular control of chemical and physical chain properties. Nature utilizes this control to formulate protein polymers into materials with extraordinary mechanical properties, such as the strength and toughness of silk and the elasticity and resilience of mammalian elastin. The properties of these materials have been attributed to the presence of short repeating oligopeptide sequences contained in the proteins, fibroin, and elastin. We have produced homoblock protein polymers consisting exclusively of silk-like crystalline blocks and elastin-like flexible blocks. We have demonstrated that each homoblock polymer as produced by microbial fermentation exhibits measurable properties of crystallinity and elasticity. Additionally, we have produced alternating block copolymers of various amounts of silk-like and elastin-like blocks, ranging from a ratio of 1:4 to 2:1, respectively. The crystallinity of each copolymer varies with the amount of crystalline block interruptions. The production of fiber materials with custom-engineered mechanical properties is a potential outcome of this technology.     

Overview of bacterial cellulose composites: A multipurpose advanced material

Bacterial cellulose (BC) has received substantial interest owing to its unique structural features and impressive physico-mechanical properties. BC has a variety of applications in biomedical fields, including use as biomaterial for artificial skin, artificial blood vessels, vascular grafts, scaffolds for tissue engineering, and wound dressing. However, pristine BC lacks certain properties, which limits its applications in various fields; therefore, synthesis of BC composites has been conducted to address these limitations. A variety of BC composite synthetic strategies have been developed based on the nature and relevant applications of the combined materials. BC composites are primarily synthesized through in situ addition of reinforcement materials to BC synthetic media or the ex situ penetration of such materials into BC microfibrils. Polymer blending and solution mixing are less frequently used synthetic approaches. BC composites have been synthesized using numerous materials ranging from organic polymers to inorganic nanoparticles. In medical fields, these composites are used for tissue regeneration, healing of deep wounds, enzyme immobilization, and synthesis of medical devices that could replace cardiovascular and other connective tissues. Various electrical products, including biosensors, biocatalysts, E-papers, display devices, electrical instruments, and optoelectronic devices, are prepared from BC composites with conductive materials. In this review, we compiled various synthetic approaches for BC composite synthesis, classes of BC composites, and applications of BC composites. This study will increase interest in BC composites and the development of new ideas in this field.     

Polypeptoid polymers: Synthesis,characterization, and properties

Polypeptoids, a class of peptidomimetic polymers, have emerged at the forefront of macromolecular and supramolecular science and engineering as the technological relevance of these polymers continues to be demonstrated. The chemical and structural diversity of polypeptoids have enabled access to and adjustment of a variety of physicochemical and biological properties (eg, solubility, charge characteristics, chain conformation, HLB, thermal processability, degradability, cytotoxicity and immunogenicity). These attributes have made this synthetic polymer platform a potential candidate for various biomedical and biotechnological applications. This review will provide an overview of recent development in synthetic methods to access polypeptoid polymers with well‐defined structures and highlight some of the fundamental physicochemical and biological properties of polypeptoids that are pertinent to the future development of functional materials based on polypeptoids.     

Delivery of bone morphogenetic proteins for orthopedic tissue regeneration

Carriers for bone morphogenetic proteins (BMPs) are used to increase retention of these factors at orthopedic treatment sites for a sufficient period of time to allow regenerative tissue forming cells to migrate to the area of injury and to proliferate and differentiate. Carriers can also serve as a matrix for cell infiltration while maintaining the volume in which repair tissue can form. Carriers have to be biocompatible and are often required to be bioresorbable. Carriers also have to be easily, and cost-effectively, manufactured for large-scale production, conveniently sterilized and have appropriate storage requirements and stability. All of these processes have to be approvable by regulatory agencies. The four major categories of BMP carrier materials include natural polymers, inorganic materials, synthetic polymers, composites of these materials. Autograft or allograft carriers have also used. Carrier configurations range from simple depot delivery systems to more complex systems mimicking the extracellular matrix structure and function. Bone regenerative carriers include depot delivery systems for fracture repair, three-dimensional polymer or ceramic composites for segmental repairs and spine fusion and metal or metal/ceramic composites for augmenting implant integration. Tendon/ligament regenerative carriers range from depot delivery systems to three-dimensional carriers that are either randomly oriented or linearly oriented to improve regenerative tissue alignment. Cartilage regenerative systems generally require three-dimensional matrices and often incorporate cells in addition to factors to augment the repair. Alternative BMP delivery systems include viral vectors, genetically altered cells, conjugated factors and small molecules.