Large-area, self-healing block copolymer membranes for energy conversion.

Membranes are widely used for separation processes in applications such as water desalination, batteries and dialysis, and are crucial in key sectors of our economy and society1. The majority of technologically exploited membranes are based on solid polymers and function as passive barriers, whose transport characteristics are governed by their chemical composition and nanostructure. Although such membranes are ubiquitous, it has proved challenging to maximize selectivity and permeability independently, leading to trade-offs between these pertinent characteristics2. Self-assembled biological membranes, in which barrier and transport functions are decoupled3,4, provide the inspiration to address this problem5,6. Here we introduce a self-assembly strategy that uses the interface of an aqueous two-phase system to template and stabilize molecularly thin (approximately 35 nm) biomimetic block copolymer bilayers of scalable area that can exceed 10 cm2 without defects. These membranes are self-healing, and their barrier function against the passage of ions (specific resistance of approximately 1 MΩ cm2) approaches that of phospholipid membranes. The fluidity of these membranes enables straightforward functionalization with molecular carriers that shuttle potassium ions down a concentration gradient with exquisite selectivity over sodium ions. This ion selectivity enables the generation of electric power from equimolar solutions of NaCl and KCl in devices that mimic the electric organ of electric rays.

Mechanically triggered on-demand degradation of polymers synthesized by radical polymerizations.

Polymers that degrade on demand have the potential to facilitate chemical recycling, reduce environmental pollution and are useful in implant immolation, drug delivery or as adhesives that debond on demand. However, polymers made by radical polymerization, which feature all carbon-bond backbones and constitute the most important class of polymers, have proven difficult to render degradable. Here we report cyclobutene-based monomers that can be co-polymerized with conventional monomers and impart the resulting polymers with mechanically triggered degradability. The cyclobutene residues act as mechanophores and can undergo a mechanically triggered ring-opening reaction, which causes a rearrangement that renders the polymer chains cleavable by hydrolysis under basic conditions. These cyclobutene-based monomers are broadly applicable in free radical and controlled radical polymerizations, introduce functional groups into the backbone of polymers and allow the mechanically gated degradation of high-molecular-weight materials or cross-linked polymer networks into low-molecular-weight species.

Artificial cell synthesis using biocatalytic polymerization-induced self-assembly.

Artificial cells are biomimetic microstructures that mimic functions of natural cells, can be applied as building blocks for molecular systems engineering, and host synthetic biology pathways. Here we report enzymatically synthesized polymer-based artificial cells with the ability to express proteins. Artificial cells were synthesized using biocatalytic atom transfer radical polymerization-induced self-assembly, in which myoglobin synthesizes amphiphilic block co-polymers that self-assemble into structures such as micelles, worm-like micelles, polymersomes and giant unilamellar vesicles (GUVs). The GUVs encapsulate cargo during the polymerization, including enzymes, nanoparticles, microparticles, plasmids and cell lysate. The resulting artificial cells act as microreactors for enzymatic reactions and for osteoblast-inspired biomineralization. Moreover, they can express proteins such as a fluorescent protein and actin when fed with amino acids. Actin polymerizes in the vesicles and alters the artificial cells' internal structure by creating internal compartments. Thus, biocatalytic atom transfer radical polymerization-induced self-assembly-derived GUVs can mimic bacteria as they are composed of a microscopic reaction compartment that contains genetic information for protein expression upon induction.

Self-decorating cells via surface-initiated enzymatic controlled radical polymerization.

Through the innovative use of surface-displayed horseradish peroxidase, this work explores the enzymatic catalysis of both bioRAFT polymerization and bioATRP to prompt polymer synthesis on the surface of Saccharomyces cerevisiae cells, with bioATRP outperforming bioRAFT polymerization. The resulting surface modification of living yeast cells with synthetic polymers allows for a significant change in yeast phenotype, including growth profile, aggregation characteristics, and conjugation of non-native enzymes to the clickable polymers on the cell surface, opening new avenues in bioorthogonal cell-surface engineering.

Visible light-responsive materials: the (photo)chemistry and applications of donor-acceptor Stenhouse adducts in polymer science.

Donor-acceptor Stenhouse adduct (DASA) photoswitches have gained a lot of attention since their discovery in 2014. Their negative photochromism, visible light absorbance, synthetic tunability, and the large property changes between their photoisomers make them attractive candidates over other commonly used photoswitches for use in materials with responsive or adaptive properties. The development of such materials and their translation into advanced technologies continues to widely impact forefront materials research, and DASAs have thus attracted considerable interest in the field of visible-light responsive molecular switches and dynamic materials. Despite this interest, there have been challenges in understanding their complex behavior in the context of both small molecule studies and materials. Moreover, incorporation of DASAs into polymers can be challenging due to their incompatibility with the conditions for most common polymerization techniques. In this review, therefore, we examine and critically discuss the recent developments and challenges in the field of DASA-containing polymers, aiming at providing a better understanding of the interplay between the properties of both constituents (matrix and photoswitch). The first part summarizes current understanding of DASA design and switching properties. The second section discusses strategies of incorporation of DASAs into polymers, properties of DASA-containing materials, and methods for studying switching of DASAs in materials. We also discuss emerging applications for DASA photoswitches in polymeric materials, ranging from light-responsive drug delivery systems, to photothermal actuators, sensors and photoswitchable surfaces. Last, we summarize the current challenges in the field and venture on the steps required to explore novel systems and expand both the functional properties and the application opportunities of DASA-containing polymers.

An Outer Membrane-Inspired Polymer Coating Protects and Endows Escherichia coli with Novel Functionalities.

A bio-inspired membrane made of Pluronic L-121 is produced around Escherichia coli thanks to the simple co-extrusion of bacteria and polymer vesicles. The block copolymer-coated bacteria can withstand various harsh shocks, for example, temperature, pressure, osmolarity, and chemical agents. The polymer membrane also makes the bacteria resistant to enzymatic digestion and enables them to degrade toxic compounds, improving their performance as whole-cell biocatalysts. Moreover, the polymer membrane acts as an anchor layer for the surface modification of the bacteria. Being decorated with α-amylase or lysozyme, the cells are endowed with the ability to digest starch or self-predatory bacteria are created. Thus, without any genetic engineering, the phenotype of encapsulated bacteria is changed as they become sturdier and gain novel metabolic functionalities.

Encapsulation of Fragrances in Micro- and Nano-Capsules, Polymeric Micelles, and Polymersomes.

Fragrances are ubiquitously and extensively used in everyday life and several industrial applications, including perfumes, textiles, laundry formulations, hygiene household products, and food products. However, the intrinsic volatility of these small organic molecules leaves them particularly susceptible to fast depletion from a product or from the surface they have been applied to. Encapsulation is a very effective method to limit the loss of fragrance during their use and to sustain their release. This review gives an overview of the different materials and techniques used for the encapsulation of fragrances, scents, and aromas, as well as the methods used to characterize the resulting encapsulation systems, with a particular focus on cyclodextrins, polymer microcapsules, inorganic microcapsules, block copolymer micelles, and polymersomes for fragrance encapsulation, sustained release, and controlled release.

Donor-acceptor Stenhouse adduct functionalised polymer microspheres.

Polymers that carry donor-acceptor Stenhouse adducts (DASAs) are a very relevant class of light-responsive materials. Capable of undergoing reversible, photoinduced isomerisations under irradiation with visible light, DASAs allow for on-demand property changes to be performed in a non-invasive fashion. Applications include photothermal actuation, wavelength-selective biocatalysis, molecular capture and lithography. Typically, such functional materials incorporate DASAs either as dopants or as pendent functional groups on linear polymer chains. By contrast, the covalent incorporation of DASAs into crosslinked polymer networks is under-explored. Herein, we report DASA-functionalised crosslinked styrene-divinylbenzene-based polymer microspheres and investigate their light-induced property changes. This presents the opportunity to expand DASA-material applications into microflow assays, polymer-supported reactions and separation science. Poly(divinylbenzene-co-4-vinylbenzyl chloride-co-styrene) microspheres were prepared by precipitation polymerisation and functionalised via post-polymerisation chemical modification reactions with 3rd generation trifluoromethyl-pyrazolone DASAs to varying extents. The DASA content was verified via 19F solid-state NMR (ssNMR), and DASA switching timescales were probed by integrated sphere UV-Vis spectroscopy. Irradiation of DASA functionalised microspheres led to significant changes in their properties, notably improving their swelling in organic and aqueous environments, dispersibility in water and increasing mean particle size. This work sets the stage for future developments of light-responsive polymer supports in solid-phase extraction or phase transfer catalysis.

Polymersome-based protein drug delivery - quo vadis?

Protein-based therapeutics are an attractive alternative to established therapeutic approaches and represent one of the fastest growing families of drugs. While many of these proteins can be delivered using established formulations, the intrinsic sensitivity of proteins to denaturation sometimes calls for a protective carrier to allow administration. Historically, lipid-based self-assembled structures, notably liposomes, have performed this function. After the discovery of polymersome-based targeted drug-delivery systems, which offer manifold advantages over lipid-based structures, the scientific community expected that such systems would take the therapeutic world by storm. However, no polymersome formulations have been commercialised. In this review article, we discuss key obstacles for the sluggish translation of polymersome-based protein nanocarriers into approved pharmaceuticals, which include limitations imparted by the use of non-degradable polymers, the intricacies of polymersome production methods, and the complexity of the in vivo journey of polymersomes across various biological barriers. Considering this complex subject from a polymer chemist's point of view, we highlight key areas that are worthy to explore in order to advance polymersomes to a level at which clinical trials become worthwhile and translation into pharmaceutical and nanomedical applications is realistic.

Engineered myoglobin as a catalyst for atom transfer radical cyclisation.

Myoglobin was subjected to site-directed mutagenesis and transformed into a catalyst able to perform atom transfer radical cyclisation reactions, i.e. intramolecular atom transfer radical additions. Replacing the iron-coordinating histidine with serine, or introducing small changes inside or at the entrance of the active site, transformed the completely inactive wild-type myoglobin into an artificial metalloenzyme able to catalyse the 5-exo cyclisation of halogenated unsaturated compounds for the synthesis of γ-lactams. This new-to-nature activity was achieved not only with purified protein but also in crude cell lysate and in whole cells.

Peroxidase Activity of Myoglobin Variants Reconstituted with Artificial Cofactors.

Myoglobin (Mb) can react with hydrogen peroxide (H2 O2 ) to form a highly active intermediate compound and catalyse oxidation reactions. To enhance this activity, known as pseudo-peroxidase activity, previous studies have focused on the modification of key amino acid residues of Mb or the heme cofactor. In this work, the Mb scaffold (apo-Mb) was systematically reconstituted with a set of cofactors based on six metal ions and two ligands. These Mb variants were fully characterised by UV-Vis spectroscopy, circular dichroism (CD) spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS) and native mass spectrometry (nMS). The steady-state kinetics of guaiacol oxidation and 2,4,6-trichlorophenol (TCP) dehalogenation catalysed by Mb variants were determined. Mb variants with iron chlorin e6 (Fe-Ce6) and manganese chlorin e6 (Mn-Ce6) cofactors were found to have improved catalytic efficiency for both guaiacol and TCP substrates in comparison with wild-type Mb, i. e. Fe-protoporphyrin IX-Mb. Furthermore, the selected cofactors were incorporated into the scaffold of a Mb mutant, swMb H64D. Enhanced peroxidase activity for both substrates were found via the reconstitution of Fe-Ce6 into the mutant scaffold.

A Methodology for Remote Microwave Sterilization Applicable to the Coronavirus and Other Pathogens Using Retrodirective Antenna Arrays.

This paper describes an innovative remote surface sterilization approach applicable to the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The process is based on the application of a liquid film on the surface or object under sterilization (OUS). A beacon signal is used to self-steer the transmitted power from the designed retrodirective antenna array (RDA) towards the OUS using circularly polarized fields; then, the sterilization is completed by raising and maintaining the required temperature for a certain time. Results suggest that the process takes 5 minutes or less for an angular coverage range over 60 degrees whilst abiding by the relevant safety protocols. This paper also models the power incident onto the OUS, providing consistent results with full-wave simulations. A practical RDA system is developed using a 2 × 1 microstrip patch array operating at 2.5 GHz and tested through the positioning of a representative target surface. Measurements, developed by sampling the power transmitted by the heterodyne RDA, are reported for various distances and angles, operating in the near-field of the system. To further validate the methodology, an additional experiment investigating virus deactivation through microwave heating was also developed. Measurements have been performed with an open cavity microwave oven on the Coronavirus (strain 229E) and egg white protein in a cuvette. This demonstrates that the temperature increases of aqueous films up to 70 [Formula: see text]C by remote microwave-induced heat can denature proteins and deactivate viruses. Possible applications of the method include sterilization of ambulances, medical equipment, and internet of things (IoT) devices.

Polymersomes-Mediated Delivery of CSF1R Inhibitor to Tumor Associated Macrophages Promotes M2 to M1-Like Macrophage Repolarization.

The crosstalk between cancer cells and tumor associated macrophages (TAMs) within the tumor environment modulates tumor progression at all stages of cancer disease. TAMs are predominantly M2-like polarized macrophages with tumor-promoting activities. Nonetheless, they can be repolarized to tumoricidal M1-like macrophages through macrophage colony stimulating factor 1 receptor inhibition (CSF1Ri). CSF1Ri is being explored as multifaced therapeutic approach to suppress TAMs tumor-promoting functions and reduce cancer cell aggressiveness and viability. However, treatment with CSF1Ri results in significant TAMs death, thereby extinguishing the possibility of generating tumoricidal M1-like macrophages. Immunotherapy has not only improved overall patient's survival in some cancer types, but also caused frequent off-target toxicity. Approaches to balance efficacy versus toxicity are needed. Herein, a CSF1Ri-loaded polymersomes (PMs) based delivery platform is developed to promote M2-like macrophage repolarization. When testing in vitro on primary human monocyte-derived macrophages (MDMs), CSF1Ri-loaded PMs are preferentially taken up by M2-like macrophages and enhance M2 to M1-like macrophage repolarization while minimizing cytotoxicity in comparison to the free drug. When testing in a MDMs-MDA-MB-231 breast cancer cell coculture model, CSF1Ri-loaded PMs further retain their M2 to M1-like macrophages polarization capacity. This CSF1Ri-loaded PM-based platform system represents a promising tool for macrophage-based immunotherapy approaches.

Donor-Acceptor Stenhouse Adduct-Polydimethylsiloxane-Conjugates for Enhanced Photoswitching in Bulk Polymers.

Donor-acceptor Stenhouse adducts (DASAs) are a rapidly emerging class of visible light-activated photochromes and DASA-functionalized polymers hold great promise as biocompatible photoresponsive materials. However, the photoswitching performance of DASAs in solid polymer matrices is often low, particularly in materials below their glass transition temperature. To overcome this limitation, DASAs are conjugated to polydimethylsiloxanes which have a glass transition temperature far below room temperature and which can create a mobile molecular environment around the DASAs for achieving more solution-like photoswitching kinetics in bulk polymers. The dispersion of DASAs conjugated to such flexible oligomers into solid polymer matrices allows for more effective and tunable DASA photoswitching in stiff polymers, such as poly(methyl methacrylate), without requiring modifications of the matrix. The photoswitching of conjugates with varying polymer molecular weight, linker type, and architecture is characterized via time-dependent UV-vis spectroscopy in organic solvents and blended into polymethacrylate films. In addition, DASA-functionalized polydimethylsiloxane networks, accessible via the same synthetic route, provide an alternative solution for achieving fast and efficient DASA photoswitching in the bulk owing to their intrinsic softness and flexibility. These findings may contribute to the development of DASA-functionalized materials with better tunable, more effective, and more reversible modulation of their optical properties.

Bioengineered Protein Nanocage by Small Heat Shock Proteins Delivering mTERT siRNA for Enhanced Colorectal Cancer Suppression.

The efficient delivery of small interfering RNA (siRNA) for target gene silencing holds great promise for cancer therapy. Protein nanocages have attracted considerable attention as ideal drug delivery systems because of their material-derived advantages and unique structural properties. However, most studies about siRNA delivery have not indicated the real role of protein nanocages in inhibiting tumor growth in vivo. Herein, we fabricated an efficient siRNA delivery system using a small heat shock protein (Hsp) nanocage decorated with Arg-Gly-Asp (RGD) and the transactivator of transcription (Tat) peptide. Hsp-Tat-RGD NC showed good cellular uptake and lysosomal escape in colorectal cancer cells. In addition, the nanocage could efficiently transfect siRNA into the cytoplasmic area of CT26 cells. Hsp-Tat-RGD NC delivering telomerase reverse transcriptase (TERT)-targeting siRNA could significantly downregulate TERT protein expression and trigger tumor cell apoptosis in vitro. More importantly, Hsp-Tat-RGD/siTERT complexes nearly completely inhibited the tumor growth after five times of treatment in mice bearing CT26 xenograft. Our results demonstrate the great potential of the Tat/RGD-decorated Hsp nanocage as a promising siRNA delivery platform for cancer therapy.

[Update on 3D printing in the surgery of musculoskeletal tumors]. / Update 3D-Druck in der Chirurgie muskuloskeletaler Tumoren.

The importance of 3D printing applications in the surgery of musculoskeletal tumors has increased in recent years. Even prior to the era of 3D printing, computer-assisted techniques, such as navigation, have proved their utility. Due to the variable appearance of bone tumors, there is a need for individual solutions. The 3D printing can be used for the development of anatomical demonstration models, the construction of patient-specific instruments and custom-made implants. For these three applications, different regulatory hurdles exist. Especially for the resection of pelvic tumors, 3D printing technologies seem to provide advantages due to the complicated anatomy and the proximity to relevant neurovascular structures. With the introduction of titanium printing, construction of individualized implants that fit exactly into the defect became feasible.

[3D printing in the field of shoulder surgery]. / 3D-Druck im Bereich der Schulterchirurgie.

The 3D printing technology is a relatively new procedure with a high potential, especially in the field of shoulder surgery. The 3D printing procedures are increasingly being developed and also gaining new users. Principally, 3D printing procedures can be applied preoperatively in planning the surgical procedure, patient clarification and in teaching; however, the technology is increasing being used intraoperatively. In addition to intraoperative visualization of the models, 3D printing permits the use of individual and specific instruments and implants. This allows the precise transfer of the preoperative planning to the surgical procedure. Inaccuracies are mainly caused by soft tissues. The 3D printing can be beneficial in the fields of arthroplasty, shoulder instability as well as orthopedic trauma. The literature shows promising results in relation to duration of surgery, blood loss and clinical results of the procedure. On the other hand, it is still unclear which indications warrant the use of 3D printing. Other aspects that raise questions are the time of planning, the production time and the additional cost that the use of 3D printing entails. Nonetheless, 3D printing represents a meaningful enhancement of the portfolio of surgeons, which becomes highly beneficial and useful in complex situations. Furthermore, this procedure enables a certain amount of flexibility when reacting to certain circumstances.

[Treatment strategies for tumor-related pathological fractures of the extremities]. / Versorgungsstrategien bei tumorbedingten pathologischen Frakturen der Extremitäten.

Pathological fractures of the extremities frequently lead to uncertainty with respect to the treatment strategy and timing. The origin of metastases is typically breast, bronchial, renal and prostate cancer and myelomas. Primary bone tumors play a subordinate role. The majority affect the femur, humerus and occasionally the tibia. Surgery is typically the first line treatment as healing under conservative treatment is unlikely. The most important goal is to relieve pain and the preservation or restoration of function. For correct assessment of indications, analysis of the fracture pattern and oncological aspects including dignity, entity, prognosis, metastatic status and the general condition of the patient need to be taken into consideration. Based on all these aspects the surgical approach can be chosen. Treatment options range from osteosynthetic stabilization and augmentation osteosynthesis up to endoprosthesis replacement. The treatment is carried out in an interdisciplinary procedure as additional measures need to be addressed in addition to the surgical treatment.

Nano-3D-Printed Photochromic Micro-Objects.

Molecular photoswitches that can reversibly change color upon irradiation are promising materials for applications in molecular actuation and photoresponsive materials. However, the fabrication of photochromic devices is limited to conventional approaches such as mold casting and spin-coating, which cannot fabricate complex structures. Reported here is the first photoresist for direct laser writing of photochromic 3D micro-objects via two-photon polymerization. The integration of photochromism into thiol-ene photo-clickable resins enables rapid two-photon laser processing of highly complex microstructures and facile postmodification using a series of donor-acceptor Stenhouse adduct (DASA) photoswitches with different excitation wavelengths. The versatility of thiol-ene photo-click reactions allows fine-tuning of the network structure and physical properties as well as the type and concentration of DASA. When exposed to visible light, these microstructures exhibit excellent photoresponsiveness and undergo reversible color-changing via photoisomerization. It is demonstrated that the fluorescence variations of DASAs can be used as a reporter of photoswitching and thermal recovery, allowing the reading of DASA-containing sub-micrometric structures in 3D. This work delivers a new approach for custom microfabrication of 3D photochromic objects with molecularly engineered color and responsiveness.

Infiltration of Proteins in Cholesteric Cellulose Structures.

Cellulose nanocrystals (CNCs) can spontaneously self-assemble into chiral nematic (cn) structures, similar to natural cholesteric organizations. The latter display highly dissipative fracture propagation mechanisms given their "brick" (particles) and "mortar" (soft matrix) architecture. Unfortunately, CNCs in liquid media have strong supramolecular interactions with most macromolecules, leading to aggregated suspensions. Herein, we describe a method to prepare nanocomposite materials from chiral nematic CNCs (cn-CNCs) with strongly interacting secondary components. Films of cn-CNCs were infiltrated at various loadings with strongly interacting silk proteins and bovine serum albumin. For comparison and to determine the molecular weight range of macromolecules that can infiltrate cn-CNC films, they were also infiltrated with a range of poly(ethylene glycol) polymers that do not interact strongly with CNCs. The extent and impact of infiltration were evaluated by studying the optical reflection properties of the resulting hybrid materials (UV-vis spectroscopy), while fracture dissipation mechanisms were observed via electron microscopy. We propose that infiltration of cn-CNCs enables the introduction of virtually any secondary phase for nanocomposite formation that is otherwise not possible using simple mixing or other conventional approaches.