Merging Plastics, Microbes, and Enzymes: Highlights from an International Workshop.

In the Anthropocene, plastic pollution is a worldwide concern that must be tackled from different viewpoints, bringing together different areas of science. Microbial transformation of polymers is a broad-spectrum research topic that has become a keystone in the circular economy of fossil-based and biobased plastics. To have an open discussion about these themes, experts in the synthesis of polymers and biodegradation of lignocellulose and plastics convened within the framework of The Transnational Network for Research and Innovation in Microbial Biodiversity, Enzymes Technology and Polymer Science (MENZYPOL-NET), which was recently created by early-stage scientists from Colombia and Germany. In this context, the international workshop "Microbial Synthesis and Degradation of Polymers: Toward a Sustainable Bioeconomy" was held on 27 September 2021 via Zoom. The workshop was divided into two sections, and questions were raised for discussion with panelists and expert guests. Several key points and relevant perspectives were delivered, mainly related to (i) the microbial evolution driven by plastic pollution; (ii) the relevance of and interplay between polymer structure/composition, enzymatic mechanisms, and assessment methods in plastic biodegradation; (iii) the recycling and valorization of plastic waste; (iv) engineered plastic-degrading enzymes; (v) the impact of (micro)plastics on environmental microbiomes; (vi) the isolation of plastic-degrading (PD) microbes and design of PD microbial consortia; and (vii) the synthesis and applications of biobased plastics. Finally, research priorities from these key points were identified within the microbial, enzyme, and polymer sciences.

Aggregation-Induced Emission Boosting the Study of Polymer Science.

The past one hundred years have witnessed the great development of polymer science. The advancement of polymer science is closely related with the development of characterization techniques and methods, from viscometry in molecular weight determination to advanced techniques including differential scanning calorimetry, nuclear magnetic resonance, and scanning electron microscopy. However, these techniques are normally constrained to tedious sample preparation, high costs, harsh experimental conditions, or ex situ characterization. Fluorescence technology has the merits of high sensitivity and direct visualization. Contrary to conventional aggregation-causing quenching fluorophores, those dyes with aggregation-induced emission (AIE) characteristics show high emission efficiency in aggregate states. Based on the restriction of intramolecular motions for AIE properties, the AIE materials are very sensitive to the surrounding microenvironments owing to the twisted propeller-like structures and therefore offer great potential in the study of polymers. The AIE concept has been successfully used in polymer science and provides a deeper understanding on polymer structure and properties. In this review, the applications of AIEgens in polymer science for visualizing polymerization, glass transition, dissolution, crystallization, gelation, self-assembly, phase separation, cracking, and self-healing are exemplified and summarized. Lastly, the challenges and perspectives in the study of polymer science using AIEgens are addressed.

Exploiting Polymeric Films as a Multipurpose Drug Delivery System: a Review.

Polymeric films are drug delivery systems that maintain contact with the delivery tissue and sustain a controlled release of therapeutic molecules. These systems allow a longer time of drug contact with the target site in the case of topical treatments and allow the controlled administration of drugs. They can be manufactured by various methods such as solvent casting, hot melt extrusion, electrospinning, and 3D bioprinting. Furthermore, they can employ various polymers, for example PVP, PVA, cellulose derivatives, chitosan, gelling gum, pectin, and alginate. Its versatility is also applicable to different routes of administration, as it can be administered to the skin, oral mucosa, vaginal canal, and eyeballs. All these factors allow numerous combinations to obtain a better treatment. This review focuses on exploring some possible ways to develop them and some particularities and advantages/disadvantages in each case. It also aims to show the versatility of these systems and the advantages and disadvantages in each case, as they bring the opportunity to develop different medicines to facilitate therapies for the most diverse purposes .

Navigating the Biological-Material Interface with the Guide of Chemical Biology.

Research at the biological-material interface often has translation in mind, with applications in medical implants, drug delivery, and regenerative medicine. While the clinical impact of this research is undeniable, a clearer picture of the in vivo behavior of materials is needed to address longstanding limitations in performance and function. Advances in chemical biology and biotechnology have propelled our understanding of how small molecules and biologics behave in living systems. Adapting these techniques to the study of synthetic materials, enabled by modern polymer chemistry, will bring molecular resolution to biological-material interactions and guide the development of next-generation biomaterials for therapeutic and diagnostic applications.

Mediating Reaction Orthogonality in Polymer and Materials Science.

Selective control of chemical reactions is critical for the proper regulation of processes ranging from intricate biological systems to large scale industrial manufacturing. The progression of synthetic chemistry toward the complexity seen in Nature requires increased control over many concurrent chemical reactions in a non-interfering (orthogonal) fashion. Fortunately, the practically endless pool of synthetic chemical reactions developed to date can often be combined in an orthogonal manner to provide elegant solutions to complex chemical problems. In this review, we first highlight some of the many photochemical reactions that have been applied in orthogonal reaction protocols; the highly selective nature of photochemical reactions makes them well-suited for independent activation in the presence of other reaction components. The application of these orthogonal reactions, especially photochemical reactions, for the synthesis and modification of polymers and polymeric materials is also summarized. Importantly, the use of orthogonal chemical reactions can provide additional opportunities for synthesizing advanced and functional polymeric materials compared to traditional synthetic procedures.

The CuAAC: Principles, Homogeneous and Heterogeneous Catalysts, and Novel Developments and Applications.

The copper-catalyzed azide/alkyne cycloaddition reaction (CuAAC) has emerged as the most useful "click" chemistry. Polymer science has profited enormously from CuAAC by its simplicity, ease, scope, applicability and efficiency. Basic principles of the CuAAC are reviewed with a focus on homogeneous and heterogeneous catalysts, ligands, anchimeric assistance, and basic chemical principles. Recent developments of ligand design and acceleration are discussed.

Cyclic Polymers by Ring-Closure Strategies.

The preparation of cyclic macromolecules has always represented a challenging task for polymer science, mainly because of difficulties in connecting chain extremities together. Initiated by the pioneering studies of Jacobson and Stockmayer, preparative pathways to cyclic polymers have been considerably improved within the last two decades thanks to the advent of both controlled polymerizations and efficient coupling reactions in organic chemistry. This Review aims to provide a critical up-to-date overview and illustrate the considerable efforts that have been made in the past few years to improve the availability of macrocycles for industrial and academic investigations through the use of the ring-closure approach. Particular attention is paid to methods for the preparation of monocycles over more complex architectures, since the latter are usually derived from the former.

Optimizing enzyme-responsive polymersomes for protein-based therapies.

Aims: Stimuli-responsive polymersomes are promising tools for protein-based therapies, but require deeper understanding and optimization of their pathology-responsive behavior. Materials & methods: Hyaluronic acid (HA)-poly(b-lactic acid) (PLA) polymersomes self-assembled from block copolymers of varying molecular weights of HA were compared for their physical properties, degradation and intracellular behavior. Results: Major results showed increasing enzyme-responsivity associated with decreasing molecular weight. The major formulation differences were as follows: the HA(5 kDa)-PLA formulation exhibited the most pronounced release of encapsulated proteins, while the HA(7 kDa)-PLA formulation showed the most different release behavior from neutral. Conclusion: We have discovered design rules for HA-PLA polymersomes for protein delivery, with lower molecular weight leading to higher encapsulation efficiency, greater release and greater intracellular uptake.

Numerical Study of the Effect of High Gravity in Material Extrusion System and Polymer Characteristics during Filament Fabrication.

Polymer science plays a crucial role in the understanding and numerical study of material extrusion processes that have revolutionized additive manufacturing (AM). This study investigated the impact of high-gravity conditions on material extrusion and conducted a numerical study by referring to the development of a high-gravity material extrusion system (HG-MEX). In this study, we evaluated the polymeric characteristics of HG-MEX. By analyzing the interplay between polymer behavior and gravity, we provide insights into the effects of high gravity on extrusion processes, including filament flow, material deposition, and the resulting fabrication characteristics. The established numerical study of high-gravity material extrusion in additive manufacturing is a meaningful and valuable approach for improving the quality and efficiency of the process. This study is unique in that it incorporates material surface characteristics to represent the performance and contact with polymer science in additive manufacturing. The findings presented herein contribute to a broader understanding of polymer science and its practical implications for HG-MEX under various gravitational conditions.

Reusable Macroporous Oil Sorbent Films from Plastic Wastes.

Plastic waste comprises 15% of the total municipal solid waste and can be a rich source for producing value-added materials. Among them, polyethylene (PE) and polypropylene (PP) account for 60% of the total plastic waste, mainly due to their low-end and one-time-use applications. Herein, we report reusable oil sorbent films made by upcycling waste PE and PP. The as-prepared oil sorbent had an uptake capacity of 55 g/g. SEM analysis revealed a macroporous structure with a pore size range of 1-10 µm, which facilitates oil sorption. Similarly, the contact angle values reflected the oleophilic nature of the sorbent. Moreover, thermal properties and crystallinity were examined using DSC, while mechanical properties were calculated using tensile testing. Lastly, 95% of the sorbed oil could be easily recovered by squeezing mechanically or manually.

Biomedical Applications of Bacteria-Derived Polymers.

Plastics have found widespread use in the fields of cosmetic, engineering, and medical sciences due to their wide-ranging mechanical and physical properties, as well as suitability in biomedical applications. However, in the light of the environmental cost of further upscaling current methods of synthesizing many plastics, work has recently focused on the manufacture of these polymers using biological methods (often bacterial fermentation), which brings with them the advantages of both low temperature synthesis and a reduced reliance on potentially toxic and non-eco-friendly compounds. This can be seen as a boon in the biomaterials industry, where there is a need for highly bespoke, biocompatible, processable polymers with unique biological properties, for the regeneration and replacement of a large number of tissue types, following disease. However, barriers still remain to the mass-production of some of these polymers, necessitating new research. This review attempts a critical analysis of the contemporary literature concerning the use of a number of bacteria-derived polymers in the context of biomedical applications, including the biosynthetic pathways and organisms involved, as well as the challenges surrounding their mass production. This review will also consider the unique properties of these bacteria-derived polymers, contributing to bioactivity, including antibacterial properties, oxygen permittivity, and properties pertaining to cell adhesion, proliferation, and differentiation. Finally, the review will select notable examples in literature to indicate future directions, should the aforementioned barriers be addressed, as well as improvements to current bacterial fermentation methods that could help to address these barriers.

Reverse Actuation of Polyelectrolyte Effect for In Vivo Antifouling.

Zwitterionic polymers have extraordinary properties, that is, significant hydration and the so-called antipolyelectrolyte effect, which make them suitable for biomedical applications. The hydration induces an antifouling effect, and this has been investigated significantly. The antipolyelectrolyte effect refers to the extraordinary ion-responsive behavior of particular polymers that swell and hydrate considerably in physiological solutions. This actuation begins to attract attention to achieve in vivo antifouling that is challenging for general polyelectrolytes. In this study, we established the sophisticated cornerstone of the antipolyelectrolyte effect in detail, including (i) the essential parameters, (ii) experimental verifications, and (iii) effect of improving antifouling performance. First, we find that both osmotic force and charge screening are essential factors. Second, we identify the antipolyelectrolyte effect by visualizing the swelling and hydration dynamics. Finally, we verify that the antifouling performance can be enhanced by exploiting the antipolyelectrolyte effect and report reduction of 85% and 80% in ex and in vivo biofilm formation, respectively.

Histopathological analysis of zebrafish after introduction of non-biodegradable polyelectrolyte microcapsules into the circulatory system.

Polyelectrolyte microcapsules are among the most promising carriers of various sensing substances for their application inside the bloodstream of vertebrates. The long-term effects of biodegradable microcapsules in mammals are relatively well studied, but this is not the case for non-biodegradable microcapsules, which may be even more generally applicable for physiological measurements. In the current study, we introduced non-biodegradable polyelectrolyte microcapsules coated with polyethylene glycol (PMs-PEG) into the circulatory system of zebrafish to assess their long-term effects on fish internal organs with histopathologic analysis. Implantation of PMs-PEG was not associated with the formation of microclots or thrombi in thin capillaries; thus, the applied microcapsules had a low aggregation capacity. The progression of the immune response to the implant depended on the time and the abundance of microparticles in the tissues. We showed that inflammation originated from recognition and internalization of PMs-PEG by phagocytes. These microcapsule-filled immune cells have been found to migrate through the intestinal wall into the lumen, demonstrating a possible mechanism for partial microparticle elimination from fish. The observed tissue immune response to PMs-PEG was local, without a systemic effect on the fish morphology. The most pronounced chronic severe inflammatory reaction was observed near the injection site in renal parenchyma and within the abdominal cavity since PMs-PEG were administered with kidney injection. Blood clots and granulomatosis were noted at the injection site but were not found in the kidneys outside the injection site. Single microcapsules brought by blood into distal organs did not have a noticeable effect on the surrounding tissues. The severity of noted pathologies of the gills was insufficient to affect respiration. No statistically significant alterations in hepatic morphology were revealed after PMs-PEG introduction into fish body. Overall, our data demonstrate that despite they are immunogenic, non-biodegradable PMs-PEG have low potential to cause systemic effects if applied in the minimal amount necessary for detection of fluorescent signal from the microcapsules.

Engineered drug delivery devices to address Global Health challenges.

There is a dire need for innovative solutions to address global health needs. Polymeric systems have been shown to provide substantial benefit to all sectors of healthcare, especially for their ability to extend and control drug delivery. Herein, we review polymeric drug delivery devices for vaccines, tuberculosis, and contraception.

Covalent Functionalization of Bioengineered Polyhydroxyalkanoate Spheres Directed by Specific Protein-Protein Interactions.

Bioengineered polyhydroxyalkanoate (PHA) spheres assembled in engineered bacteria are showing promising potential in protein immobilization for high-value applications. Here, we have designed innovative streamlined approaches to add functional proteins from complex mixtures (e.g., without prior purification) to bioengineered PHA spheres directly harnessing the specificity of the SpyTag/SpyCatcher mediated protein ligation. Escherichia coli was engineered to assemble PHA spheres displaying the SpyCatcher domain while simultaneously producing a SpyTagged target protein, which was in vivo specifically ligated to the PHA spheres. To further demonstrate the specificity of this ligation reaction, we incubated isolated SpyCatcher-coated PHA spheres with cell lysates containing SpyTagged target protein, which also resulted in specific ligation mediating surface functionalization. An even cruder approach was used by lysing a mixture of cells, either producing PHA spheres or target protein, which resulted in specific surface functionalization suggesting that ligation between the SpyCatcher-coated PHA spheres and the SpyTagged target proteins is highly specific. To expand the design space of this general modular approach toward programmable multifunctionalization, e.g., one-pot construction of immobilized multienzyme cascade systems on PHA spheres, we designed various recombinant bimodular PHA spheres utilizing alternative Tag/Catcher pairs (e.g., SnoopTag/SnoopCatcher and SdyTag/SdyCatcher systems). One of our bimodular PHA spheres resulted in simultaneous multifunctionalization of plain PHA spheres in one-step with two differently tagged proteins under in vitro and ex vivo reaction conditions while remaining functional. Our bimodular PHA spheres also showed high orthogonality with the non-target peptide tag and exhibited decent robustness against repeated freeze-thaw treatment. We demonstrated the utility of these approaches by using a fluorescent protein, a monomeric amylase, and a dimeric organophosphate hydrolase as target proteins. We established a versatile toolbox for dynamic functionalization of PHA spheres for biomedical and industrial applications.

Computational Removal of Undesired Mass Spectral Features Possessing Repeat Units via a Kendrick Mass Filter.

Polymers are a common component of chemical background which complicates data analysis and can impair interpretation. Undesired chemical background cannot always be addressed via pre-analytical methods, chromatography, or existing data processing methods. The Kendrick mass filter (KMF) is presented for the computational removal of undesired signals present in MS1 spectra. The KMF is analogous to mass defect filtering but utilizes homology information via Kendrick mass scaling in combination with chromatographic retention time and the number of observed signals. The KMF is intended to assist in situations in which current data processing methods to remove background, e.g., blank subtraction, are either not possible or effective. The major parameters affecting KMF were investigated using PEG 400 and NIST standard reference material 1950 (metabolites in human plasma). Further exploration of the KMF performance was tested using an extract of a swab known to contain polymers. An illustrative real-world example of skin analysis with polymeric signal is discussed. The KMF is also able to provide a high-level view of the compositionality of data regarding the presence of signals with repeat units and indicate the presence of different polymers. Graphical Abstract ᅟ.

Highly Efficient In Vivo Targeting of the Pulmonary Endothelium Using Novel Modifications of Polyethylenimine: An Importance of Charge.

Pulmonary vascular disease encompasses a wide range of serious afflictions with important clinical implications. There is critical need for the development of efficient, nonviral gene therapy delivery systems. Here, a promising avenue to overcome critical issues in efficient cell targeting within the lung via a uniquely designed nanosystem is reported. Polyplexes are created by functionalizing hyperbranched polyethylenimine (PEI) with biological fatty acids and carboxylate-terminated poly(ethylene glycol) (PEG) through a one-pot 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide reaction. Following intravenous injection, polyplexes show an exceptionally high specificity to the pulmonary microvascular endothelium, allowing for the successful delivery of stabilized enhanced green fluorescent protein (eGFP) expressing messenger ribonucleic acid (mRNA). It is further shown, quantitatively, that positive surface charge is the main mechanism behind such high targeting efficiency for these polyplexes. Live in vivo imaging, flow cytometry of single cell suspensions, and confocal microscopy are used to demonstrate that positive polyplexes are enriched in the lung tissue and disseminated in 85-90% of the alveolar capillary endothelium, whilst being sparse in large vessels. Charge modification, achieved through poly(acrylic acid) or heparin coating, drives a highly significant reduction in both targeting percentage and targeting strength, highlighting the importance of specific surface charge, derived from chemical formulation, for efficient targeting of the pulmonary microvascular endothelium.

Hydrogels in a historical perspective: from simple networks to smart materials.

Over the past decades, significant progress has been made in the field of hydrogels as functional biomaterials. Biomedical application of hydrogels was initially hindered by the toxicity of crosslinking agents and limitations of hydrogel formation under physiological conditions. Emerging knowledge in polymer chemistry and increased understanding of biological processes resulted in the design of versatile materials and minimally invasive therapies. Hydrogel matrices comprise a wide range of natural and synthetic polymers held together by a variety of physical or chemical crosslinks. With their capacity to embed pharmaceutical agents in their hydrophilic crosslinked network, hydrogels form promising materials for controlled drug release and tissue engineering. Despite all their beneficial properties, there are still several challenges to overcome for clinical translation. In this review, we provide a historical overview of the developments in hydrogel research from simple networks to smart materials.

"Polymeromics": Mass spectrometry based strategies in polymer science toward complete sequencing approaches: a review.

Mass spectrometry (MS) is the most versatile and comprehensive method in "OMICS" sciences (i.e. in proteomics, genomics, metabolomics and lipidomics). The applications of MS and tandem MS (MS/MS or MS(n)) provide sequence information of the full complement of biological samples in order to understand the importance of the sequences on their precise and specific functions. Nowadays, the control of polymer sequences and their accurate characterization is one of the significant challenges of current polymer science. Therefore, a similar approach can be very beneficial for characterizing and understanding the complex structures of synthetic macromolecules. MS-based strategies allow a relatively precise examination of polymeric structures (e.g. their molar mass distributions, monomer units, side chain substituents, end-group functionalities, and copolymer compositions). Moreover, tandem MS offer accurate structural information from intricate macromolecular structures; however, it produces vast amount of data to interpret. In "OMICS" sciences, the software application to interpret the obtained data has developed satisfyingly (e.g. in proteomics), because it is not possible to handle the amount of data acquired via (tandem) MS studies on the biological samples manually. It can be expected that special software tools will improve the interpretation of (tandem) MS output from the investigations of synthetic polymers as well. Eventually, the MS/MS field will also open up for polymer scientists who are not MS-specialists. In this review, we dissect the overall framework of the MS and MS/MS analysis of synthetic polymers into its key components. We discuss the fundamentals of polymer analyses as well as recent advances in the areas of tandem mass spectrometry, software developments, and the overall future perspectives on the way to polymer sequencing, one of the last Holy Grail in polymer science.