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The extracellular matrix (ECM) plays a crucial role in organoid cultures by supporting cell proliferation and differentiation. A key feature of the ECM is its mechanical influence on the surrounding cells, directly affecting their behavior. Matrigel, the most commonly used ECM, is limited by its animal-derived origin, batch variability, and uncontrollable mechanical properties, restricting its use in 3D cell-model-based mechanobiological studies. Poly(2-alkyl-2-oxazoline) (PAOx) synthetic hydrogels represent an appealing alternative because of their reproducibility and versatile chemistry, enabling tuning of hydrogel stiffness and functionalization. Here, we studied PAOx hydrogels with differing compressive moduli for their potential to support 3D cell growth. PAOx hydrogels support spheroid and organoid growth over several days without the addition of ECM components. Furthermore, we discovered intestinal organoid epithelial polarity reversion in PAOx hydrogels and demonstrate how the tunable mechanical properties of PAOx can be used to study effects on the morphology and oxygenation of live multicellular spheroids.

Dynamic covalent chemistry (DCC) allows the development of thermally (re)processable and recyclable polymer networks, which is a highly attractive feature for new generations of thermoset materials. However, despite a surge in academic interest wherein soon almost any imaginable DCC platform may have been applied in a thermoset formulation, dynamic or reversible covalent polymer networks have so far found only few industrial applications. This Review provides a perspective on the main strategies for the application of DCC in the design and development of bulk thermoset materials, and it presents some of the key hurdles for their industrial implementation. The polymer design strategies and associated chemistries are viewed from the perspective of how 'close to market' their development pathway is, thus providing a roadmap to achieve high-volume breakthrough applications., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. Springer Nature Limited.)

Volumetric bioprinting has revolutionized the field of biofabrication by enabling the creation of cubic centimeter-scale living constructs at faster printing times (in the order of seconds). However, a key challenge remains: developing a wider variety of available osteogenic bioinks that allow osteogenic maturation of the encapsulated cells within the construct. Herein, the bioink exploiting a step-growth mechanism (norbornene-norbornene functionalized gelatin in combination with thiolated gelatin-GelNBNBSH) outperformed the bioink exploiting a chain-growth mechanism (gelatin methacryloyl-GelMA), as the necessary photo-initiator concentration was three times lower combined with a more than 50% reduction in required light exposure dose resulting in an improved positive and negative resolution. To mimic the substrate elasticity of the osteoid, two concentrations of the photo-initiator Li-TPO-L (1 and 10 mg ml -1 ) were compared for post-curing whereby the lowest concentration was selected since it resulted in attaining the osteogenic substrate elasticity combined with excellent biocompatibility with HT1080 cells (>95%). Further physico-chemical testing revealed that the volumetric printing (VP) process affected the degradation time of the constructs with volumetric constructs degrading slower than the control sheets which could be due to the introduced fibrillar structure inherent to the VP process. Moreover, GelNBNBSH volumetric constructs significantly outperformed the GelMA volumetric constructs in terms of a 2-fold increase in photo-crosslinkable moiety conversion and a 3-fold increase in bulk stiffness of the construct. Finally, a 21-day osteogenic cell study was performed with highly viable dental pulp-derived stem cells (>95%) encapsulated within the volumetric printed constructs. Osteogenesis was greatly favored for the GelNBNBSH constructs through enhanced early (alkaline phosphatase activity) and late maturation (calcium production) osteogenic markers. After 21 d, a secretome analysis revealed a more mature osteogenic phenotype within GelNBNBSH constructs as compared to their chain-growth counterpart in terms of osteogenic, immunological and angiogenic signaling., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Physical understanding and determination of different analytes without the need for advanced and additional equipment are highly important, which can be achieved by using stimuli-induced chromic materials. Physical and chemical incorporation of responsive chromophores into different polymers results in the fabrication of chromic polymers. Chromic electrospun nanofibers are prepared using the electrospinning technique, and their stimuli-responsivity is improved due to their high surface-to-volume ratio. This Perspective focuses on recent studies and developments on stimuli-induced chromic electrospun nanofibers. Within this Perspective, these nanofibers are divided into different classes of photochromic, thermochromic, electrochromic, mechanochromic, halochromic, solvatochromic, hydrochromic, and ionochromic according to the stimuli to which they respond. In addition, the preparation methods, chromic compounds, electrospinning conditions, response mechanisms, and different applications of chromic nanofibers will be discussed. The main applications of such chromic nanofibers are food packaging sensors, health monitoring sensors, anticounterfeiting materials, ink-free rewritable media, and smart clothing. Several new strategies are also proposed for different applications in future studies. The preparation of multiresponsive nanofibers that combine different chromic properties in a single system and also multifunctional nanofibers that merge stimuli-responsive chromic properties with other smart functionalities can be considered in the future. This Perspective aims to assist researchers and scientists in the preparation and development of new multifunctional chromic electrospun nanofibers for advanced applications, including multimode anticounterfeiting materials, multiresponsive sensors for food packaging, and shape memory-assisted dual-mode encryption of important data.

In recent years, polymerization-induced self-assembly (PISA) has emerged as a powerful method for the straightforward synthesis of polymer nanoparticles at high concentration. In this study, we describe for the first time the synthesis of poly(2-oxazoline) nanoparticles by dispersion cationic ring-opening polymerization-induced self-assembly (CROPISA) in n-dodecane. Specifically, a n-dodecane-soluble aliphatic poly(2-(3-ethylheptyl)-2-oxazoline) (PEHOx) block was chain-extended with poly(2-phenyl-2-oxazoline) (PPhOx). While the PhOx monomer is soluble in n-dodecane, its polymerization leads to n-dodecane-insoluble PPhOx, which leads to in situ self-assembly of the formed PEHOx-b-PPhOx copolymers. The polymerization kinetics and micellization upon second block formation were studied, and diverse nanoparticle dispersions were prepared, featuring varying block lengths and polymer concentrations, leading to dispersions with distinctive morphologies and physical properties. Finally, we developed a single-step protocol for the synthesis of polymer nanoparticles directly from monomers via gradient copolymerization CROPISA, which exploits the significantly greater reactivity of EHOx compared to that of PhOx during the statistical copolymerization of both monomers. Notably, this approach provides access to formulations with monomer compositions otherwise unattainable through the block copolymerization method. Given the synthetic versatility and application potential of poly(2-oxazolines), the developed CROPISA method can pave the way for advanced nanomaterials with favorable properties as demonstrated by using the obtained nanoparticles for stabilization of Pickering emulsions., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Addressing the global challenge of ensuring access to safe drinking water, especially in developing countries, demands cost-effective, eco-friendly, and readily available technologies. The persistence, toxicity, and bioaccumulation potential of organic pollutants arising from various human activities pose substantial hurdles. While high-performance liquid chromatography coupled with high-resolution mass spectrometry (HPLC-HRMS) is a widely utilized technique for identifying pollutants in water, the multitude of structures for a single elemental composition complicates structural identification. While current HRMS and MS/MS databases often can provide hits for known molecules, these are often erroneous or misleading when authentic standards are unavailable. In this research, a machine-learning algorithm is developed to support the structural elucidation of small organic pollutants in water, with a focus on (carbon, oxygen, and hydrogen-based) molecules weighing less than 500 Da. The approach relies on a comparison of the experimental and predicted retention of the possible structures of unknowns for which an elemental composition was obtained by HRMS. A promising novelty is thereby the improved removal of erroneous structures via the combination of the retention information obtained from two reversed-phase-based stationary phases, depicting different selectivities (octadecylsilica, C18 and pentafluorphenylsilica, F5). The study translates retention times into retention indices for instrument independence and transferability across diverse HPLC-HRMS systems. The predictive algorithm, utilizing retention data and molecular descriptors, accurately predicts retention indices and proves its utility by eliminating incorrect structural formulas through a 2-stationary phase intersection-based filtration. Using a data set of 100 training compounds and 16 external test set compounds, two Multiple Linear Regression (MLR), MLR-C18 and MLR-F5 models were developed, employing the 16 most influential descriptors, out of 5666 screened. MLR-C18 achieves precise RI predictions, R 2 = 0.96, RMSE = 44, MAE = 34. The intersection-based filtration (within ±1.5σ) showed the elimination of more than 70% of impossible structures for a given elemental composition. The model was further implemented in the identification of a drinking water sample to prove its potential. This tool holds significant promise for supporting water quality management and sustainable practices, contributing to faster structural identification of unknown organic micropollutants in water.R 2 = 0.96, RMSE = 44, MAE = 34. The intersection-based filtration (within ±1.5σ) showed the elimination of more than 70% of impossible structures for a given elemental composition. The model was further implemented in the identification of a drinking water sample to prove its potential. This tool holds significant promise for supporting water quality management and sustainable practices, contributing to faster structural identification of unknown organic micropollutants in water.

Brassinosteroids (BRs) are steroidal phytohormones indispensable for plant growth, development, and responses to environmental stresses. The export of bioactive BRs to the apoplast is essential for BR signaling initiation, which requires binding of a BR molecule to the extracellular domains of the plasma membrane-localized receptor complex. We have previously shown that the Arabidopsis thaliana ATP-binding cassette (ABC) transporter ABCB19 functions as a BR exporter and, together with its close homolog ABCB1, positively regulates BR signaling. Here, we demonstrate that ABCB1 is another BR transporter. The ATP hydrolysis activity of ABCB1 can be stimulated by bioactive BRs, and its transport activity was confirmed in proteoliposomes and protoplasts. Structures of ABCB1 were determined in substrate-unbound (apo), brassinolide (BL)-bound, and ATP plus BL-bound states. In the BL-bound structure, BL is bound to the hydrophobic cavity formed by the transmembrane domain and triggers local conformational changes. Together, our data provide additional insights into ABC transporter-mediated BR export., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hydroxyapatite (HAP) and amorphous calcium phosphate (ACP) nanoparticles were incorporated into a thiol-ene clickable gelatin network to elucidate to what extent osteogenic differentiation of human dental pulp- and adipose-derived stem cells (HDPSCs/HASCs) could be further boosted. ACP nanoparticles increased the specific surface area by 23% and reduced the density by 13% while maintaining a comparable particle size (ACP: 25 ± 3 nm; HAP: 27 ± 3 nm). Overall, the incorporation of ceramic nanoparticles did not significantly alter the mechanical properties of the ceramic-containing composites compared to the unsubstituted thiol-ene network. ACP nanoparticles at high concentrations promoted a 21-day osteogenic response in HASCs (72.09 ± 20.20 ng Ca 2+ /ng DNA) comparable to HDPSCs, with the latter showing high calcium production irrespective of the ceramic content (78.45 ± 10.87 ng Ca 2+ /ng DNA), suggesting that the provided cues must be optimized according to the investigated cell type toward a cell-interactive coating application stimulating osteogenesis.

Over the past decade, silk sericin has emerged as a promising material for biomedical applications, especially in tissue engineering, where fine-tuning the physicochemical properties is crucial. However, previous studies, including those on the methacrylation of sericin (yielding SS-MA), showed limited tunability. Here, we developed a photo-cross-linkable sericin-based material modified with 2-aminoethyl methacrylate (AEMA) using two synthesis routes: sequential modification of SS-MA with AEMA (SS-MA-AEMA) and an efficient one-pot synthesis (SS-AEMA). The one-pot synthesis yielded materials containing only methacrylate groups, unlike the sequential modification that yielded a combination of methacrylamides and methacrylates. Our approach resulted in superior physicochemical properties. The resulting materials, including the previously described SS-MA, exhibited a broad range of properties, such as cross-linking kinetics (0.9-64.0 s), swelling behavior (311-3775%), and mechanical properties (10-140 kPa). These properties support applications across various tissues, from dermis to fibrous tissue. The materials also demonstrated fibroblast cytocompatibility with cell viabilities exceeding 96%.

Background: Spectrophotometers are ubiquitous in chemical and biological science; however, their precision limits are under-appreciated. Rules-of-thumb and IUPAC referenced guidance restricting absorbance ranges to minimize uncertainty are based on historically important instruments which are no longer as widely used. Advances over the last half-century changed most "raw" data from absorbance and transmittance values directly produced in analog electronics to digitized intensities. The latter are rarely provided in favour of digitally transformed derived data. Assessment of spectrophotometer limitations using digitized intensities would be straightforward with mean-variance analysis. However, in their absence, derived data evaluated at scale allows efficient characterisation of modern spectrophotometers., Results: This study analyses signals when I and I 0 are not available and only absorbance or transmittance are obtained. Current IUPAC referenced guidance indicates that absorbance should be limited between 0.1 and 1.0 a.u. with optimal performance (minimum relative standard deviation (RSD)) at 0.43 a.u. or 0.86 a.u. depending on the type of limiting noise. We characterised noise in UV-Vis spectrophotometers using three methods and report optimality spectra for the first time. We found the instruments were not Poisson optimal and best RSDs were sometimes above 1.0 a.u. We could find no evidence justifying guidance restricting absorbance to between 0.1 and 1.0 a.u. Measured RSD and light intensity are more important than absorbance values for assuring good quality measurements. However, estimating light intensity is a difficult inverse problem when I and I 0 are not available, and the tested commercial instruments did not provide these., Significance: Based on this work, classical theories are insufficient to describe spectrophotometers accurately. Furthermore, we urge IUPAC to modernise the references in its Gold Book and press instrument makers to improve data transparency. These steps are crucial to use spectrophotometers optimally., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Poly(ɛ-caprolactone) (PCL) is a biocompatible, biodegradable, and highly mechanically resilient FDA-approved material (for specific biomedical applications, e.g. as drug delivery devices, in sutures, or as an adhesion barrier), rendering it a promising candidate to serve bone tissue engineering. However, in vivo monitoring of PCL-based implants, as well as biodegradable implants in general, and their degradation profiles pose a significant challenge, hindering further development in the tissue engineering field and subsequent clinical adoption. To address this, photo-cross-linkable mechanically resilient PCL networks are developed and functionalized with a radiopaque monomer, 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), to enable non-destructive in vivo monitoring of PCL-based implants. The covalent incorporation of AATIPA into the crosslinked PCL networks does not significantly affect their crosslinking kinetics, mechanical properties, or thermal properties, but it increases their hydrolysis rate and radiopacity. Complex and porous 3D designs of radiopaque PCL networks can be effectively monitored in vivo. This work paves the way toward non-invasive monitoring of in vivo degradation profiles and early detection of potential implant malfunctions., (© 2024 Wiley‐VCH GmbH.)

Management of hard-to-heal wounds often requires specialized care that surpasses the capabilities of conventional treatments. Even the most advanced commercial products lack the functionality to meet the needs of hard-to-heal wounds, especially those complicated by active infection, extreme bleeding, and chronic inflammation. The review explores how supramolecular nanovesicles and nanoparticles-such as dendrimers, micelles, polymersomes, and lipid-based nanocarriers-can be key to introducing advanced wound healing and monitoring properties to address the complex needs of hard-to-heal wounds. Their potential to enable advanced functions essential for next-generation wound healing products-such as hemostatic functions, transdermal penetration, macrophage polarization, targeted delivery, and controlled release of active pharmaceutical ingredients (antibiotics, gaseous products, anti-inflammatory drugs, growth factors)-is discussed via an extensive overview of the recent reports. These studies highlight that the integration of supramolecular systems in wound care is crucial for advancing toward a new generation of wound healing products and addressing significant gaps in current wound management practices. Current strategies and potential improvements regarding personalized therapies, transdermal delivery, and the promising critically evaluated but underexplored polymer-based nanovesicles, including polymersomes and proteinosomes, for wound healing., (© 2024 Wiley‐VCH GmbH.)

Recycling thermosetting materials presents itself as a major challenge in achieving sustainable material use. Dynamic covalent cross-linking of polymers has emerged as a viable solution that can combine the structural integrity of thermosetting materials with the (re-)processability of thermoplastics. Thioether linkages between polymer chains are quite common, and their use dates back to the vulcanization of rubbers. While it is known that thioether bonds can be triggered to exchange through transalkylation reactions, this process is usually slow, as thioether moieties not only have to be activated by an alkylating agent, but the activated thioether also has to associate with a second thioether moiety in a classical S N 2-type process. Here, we present the rational design of dynamic polymer networks based on simple dithiol-based monomers and a fatty acid derived triene. Two neighboring thioethers can undergo a much faster bond exchange reaction, and we found that the exchange dynamics can be further tuned over almost three orders of magnitude by tailoring the distance between two thioether functionalities. This resulted in thioether-cross-linked materials that could be processed by extrusion, a continuous reprocessing technique that was previously not accessible for this class of cross-linked materials, while still exhibiting appealing creep-resistance below 70 °C., (© 2024 Wiley-VCH GmbH.)

Non-ionic "super-hydrophilic" polymers generally possess strong non-fouling characteristics and, therefore, can suppress non-specific and unwanted interactions with blood proteins when attached to in vivo nanomedicine ranging from drug or gene delivery to diagnostics. In this contribution, we revitalize a protected alcohol functionalized 2-oxazoline monomer, 2-acetoxymethyl-2-oxazoline, that was first reported almost fifty-five years ago and explore the possibility of making "super-hydrophilic" poly(2-oxazoline)s for biomedical applications. The synthesis of the 2-acetoxymethyl-2-oxazoline monomer and its cationic ring-opening homopolymerization and copolymerization kinetics are reported. The monomer showed unanticipated and intriguing reactivity during homopolymerization as it very slowly polymerizes at low temperature while the polymerization rate constant at high temperature is amongst the highest known values. Additionally, first order kinetic plots for the copolymerisation of AcOMeOx with EtOx at high temperature revealed that AcOMeOx is incorporated at a slower rate than EtOx confirming its lower nucleophilicity, while EtOx was accelerated in the copolymerization indicating chain-end activation by the ester side-chains. Subsequently, controlled hydrolysis of the resulting poly(2-acetoxymethyl-2-oxazoline) (PAcOMeOx) generates the alcohol (-OH) side chain functional poly(2-hydroxymethyl-2-oxazoline) (PHOMeOx). The relative hydrophilicity of PHOMeOx was analyzed and compared with the previously reported most hydrophilic poly(2-oxazoline)s, such as poly(2-methoxymethyl-2-oxazoline) and poly(2-methyl-2-oxazoline), revealing that PHOMeOx is the most hydrophilic poly(2-oxazoline) reported to date. Finally, the cytocompatibility of these different hydrophilic polymers with MDA-MB-231 breast cancer cells was explored where all polymers revealed high cytocompatibility. Most importantly, strong anti-fouling properties of the most hydrophilic PHOMeOx against serum protein were observed during the cell association studies. Hence, the "super-hydrophilic" and anti-fouling PHOMeOx might be an interesting candidate to be explored in the area of polymeric drug and gene delivery as well as anti-fouling surfaces., (© 2024 Wiley-VCH GmbH.)

Reflecting on Giacomo Ciamician's revolutionary vision of harnessing sunlight to drive photochemical transformations, the field of materials science has evolved significantly, yet it has been constrained by the misconception that the highest reactivity in photochemical systems is achieved at the absorption maxima. Here, we explore this notion further with evidence from photochemical action plots, demonstrating that reactivity can indeed be maximal at wavelengths significantly separated from the absorption peak. By examining the implications of the disparity between absorptivity and photochemical reactivitiy, we explore its impact for the enhanced penetration depth of light in photoresists, the reduction of energy requirements for photochemical reactions, and its transformative potential for volumetric 3D printing. Ultimately, we argue for a renewed appreciation of light's capability to facilitate photochemical reactions across the entire volume of a material.

Light-based processing of thermosets has gained increasing attention because of its broad application field including its use in digital light processing (DLP) 3D printing. This technique offers efficient design and fabrication of complex structures but typically results in non-recyclable thermoset-based products. To address this issue, we describe here a photocurable, dynamic β-amino ester (BAE) based cross-linker that is not only suitable for DLP printing but can also be chemically degraded via transesterification upon the addition of 2-hydroxyethyl methacrylate (HEMA) as a decross-linker. This conceptually new protocol allows for efficient depolymerization with the direct restoration of curable monomers in a single step without the addition of external catalysts or solvents. By implementing this protocol, we have established a chemical recycling loop for multiple cycles of photo-cross-linking and restoration of cross-linkers, facilitating repeatable DLP 3D printing without generating any waste. The recycled materials exhibit full recovery of thermal properties and Young's modulus while maintaining 75% of their tensile strength for at least three cycles. Simultaneously, the presence of BAE moieties enables the (re)processability of these materials through compression molding.

Accurate monitoring of pesticide residues at minimal concentrations is imperative for adherence to stringent regulatory standards in numerous countries. This study presents an innovative methodology employing comprehensive two-dimensional liquid chromatography coupled with high-resolution mass spectrometry (LC × LC-HRMS). The approach ensures high sensitivity and selectivity in detecting targeted compounds. A pivotal component of this methodology is the utilization of per-aqueous liquid chromatography (PALC) as the first dimension, facilitating the use of water-based mobile phases and addressing solvent mismatch issues. The second dimension employs reversed-phase liquid chromatography (RPLC), enhancing the separation of compounds. PALC proves instrumental in refocusing and enables the practical application of narrow-diameter columns (1.5 mm I.D.). This column design permits a direct split-free connection of the LC × LC to an electrospray-based mass spectrometer (ESI-MS), contributing to heightened sensitivity. The MS acquisition is performed in a targeted single-ion monitoring mode, ensuring reliable quantification and identification of the pesticide compounds. A comprehensive evaluation of key performance metrics, including signal-to-noise ratio, limit of detection, and response linearity, is conducted. The methodology achieves a limit of detection below the ng mL -1 and exhibits response linearity within the concentration range of 1-100 ng mL -1 . The robustness of the approach is further demonstrated through intra-day and inter-day repeatability validations. Furthermore, the platform is finally tested on a surface water sample. This study not only introduces an advanced analytical methodology for pesticide multi-residue analysis but also underscores the significance of PALC in enhancing sensitivity by facilitating the use of smaller-diameter columns and water-based mobile phases, along with the role of RPLC in enhancing separation. The proposed approach showcases promising results in achieving detection limits that match the stringent regulatory standards and reliable quantification for effective pesticide residue monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Taxanes, such as paclitaxel (PTX), stabilize microtubules and are used as a first-line therapy in multiple cancer types. Disruption of microtubule equilibrium, which plays an essential role in mitosis and cell homeostasis, ultimately results in cell death. Even though PTX is a very potent chemotherapy, its use is associated with major side effects and therapy resistance. Pelophen B (PPH), a synthetic analog of peloruside A, stabilizes microtubules through interaction with a non-taxoid binding site of β-tubulin. We evaluated the anticancer effect of PPH in a variety of tumor types by using established cell lines, early-passage cultures and ex vivo tumor-derived cultures that preserve the 3D architecture of the tumor microenvironment. PPH significantly blocks colony formation capacity, reduces viability and exerts additivity with PTX. Interestingly, PPH overcomes resistance to PTX. Mechanistically, PPH induces a G2/M cell cycle arrest and increases the presence of tubulin polymerization promoting protein (TPPP), inducing lysine 40 acetylation of α-tubulin. Although, results induced by paclitaxel or PPH are concordant, PPH's unique microtubule binding mechanism enables PTX additivity and ensures overcoming PTX-induced resistance. In conclusion, PPH results in remarkable anti-cancer activity in a range of preclinical models supporting further clinical investigation of PPH as a therapeutic anticancer agent., Competing Interests: Declarations. Competing interests: Johan Vander Eycken is patentholder of Pelophen B (PCT/EP2014/075903). All other authors declare no competing interests. Ethics approval and consent to participate: Informed consent of patients to use tumor material was obtained after the study protocol was approved by the institutional review board of the Ghent University Hospital (EC 2018/0080 and ONZ-2022–0345, EC 2019/1869 and ONZ-2023-0502). All animal experiments were approved by the local ethics committee (ECD 19-45 and ECD 19-86, Ghent University Hospital). All animal experiments were conducted in accordance with the regulatory guidelines of the Ethics Committee of Ghent University Hospital and the ARRIVE guidelines., (© 2024. The Author(s).)

Dynamic polymer materials can be obtained by introducing supramolecular interactions between the polymer chains. Here we report on the preparation and mechanical properties of poly(methyl acrylate) (PMA) and poly( n -butyl acrylate) (PBA) funcionalized with ureidopyrimidinone (UPy) in the side chains. In contrast to the traditional UPy with a methyl group, the selected UPy motif contained a branched alkyl side chain, which enhances solubility, compatibility with the polymer matrix and potentially prevents stacking of UPy dimers. Low molar mass PMA and PBA were synthesized via Cu(0)-mediated radical polymerization and allyl bonds were introduced with different degrees of functionalization by stoichiometrically controlled transesterification with allyl alcohol. The allyl esters served as functional handles for UPy attachment via UV-initiated radical thiol-ene coupling. The PMA-UPy materials displayed a more glassy appearance, in contrast to the rubbery PBA-UPy polymer networks, associated to its higher glass transition temperature. The mechanical properties of the resulting hydrogen bonded polymer networks were assessed by thermogravimetric analysis, differential scanning calorimetry, dynamic mechanical thermal analysis and tensile testing, followed by rheological analysis of the network dynamics. Furthermore, the effect of associative groups on the linear viscoelastic response is discussed based on a modified sticky Rouse model indicating the absence of significant aggregation or phase separation of the UPY units.

Introduction: Advancements in resuscitative care and burn surgery have improved survival rates after extensive burn injuries, shifting focus to enhancing the quality of survival. Conventional treatment with split-thickness skin grafts (STSG) presents limitations such as donor-site morbidity, limited availability in extensive burn injuries, and hypertrophic scarring. Tissue engineering aims to address these drawbacks by developing optimal skin substitutes. This systematic review aims to provide an overview of the current applications of cultured cells in burn surgery, encompassing diverse approaches and addressing existing challenges to enhance burn wound management and improve patient outcomes., Methods: Following PRISMA guidelines, a comprehensive search was performed across three databases (PubMed, Embase, Cochrane Library) for articles on cultured cell use in burn treatment. Only clinical studies were included. Articles were screened by two independent reviewers. Quality assessment was performed., Results: The search yielded 167 articles, of which 14 met the eligibility criteria. The selection included 8 randomized controlled trials, 5 prospective cohort trials, and 1 retrospective cohort study. Various tissue-engineered skin substitutes, from cultured epidermal autografts to dermal regeneration templates seeded with cultured cells, showed promising outcomes. Several substitutes exhibited take rates comparable to STSG with improved scar quality., Conclusion: Results are promising, though standardization of cultured skin substitutes and robust clinical trials with larger populations and appropriate comparators are still lacking., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Burn injuries can result in a significant inflammatory response, often leading to hypertrophic scarring (HTS). Local drug therapies e.g. corticoid injections are advised to treat HTS, although they are invasive, operator-dependent, extremely painful and do not permit extended drug release. Polymer-based microneedle (MN) arrays can offer a viable alternative to standard care, while allowing for direct, painless dermal drug delivery with tailorable drug release profile. In the current study, we synthesized photo-crosslinkable, acrylate-endcapped urethane-based poly( ε -caprolactone) (AUP-PCL) toward the fabrication of MNs. Physico-chemical characterization ( 1 H-NMR, evaluation of swelling, gel fraction) of the developed polymer was performed and confirmed successful acrylation of PCL-diol. Subsequently, AUP-PCL, and commercially available PCL-based microneedle arrays were fabricated for comparative evaluation of the constructs. Hydrocortisone was chosen as model drug. To enhance the drug release efficiency of the MNs, Brij®35, a nonionic surfactant was exploited. The thermal properties of the MNs were evaluated via differential scanning calorimetry. Compression testing of the arrays confirmed that the MNs stay intact upon applying a load of 7 N, which correlates to the standard dermal insertion force of MNs. The drug release profile of the arrays was evaluated, suggesting that the developed PCL arrays can offer efficient drug delivery for up to two days, while the AUP-PCL arrays can provide a release up to three weeks. Finally, the insertion of MN arrays into skin samples was performed, followed by histological analysis demonstrating the AUP-PCL MNs outperforming the PCL arrays upon providing pyramidical-shaped perforations through the epidermal layer of the skin.

In this study, we developed a simple pull-down assay using peptide nucleic acids (PNAs) equipped with a His-Tag and a G-quadruplex (G4) ligand for the selective recognition and quantification of G4-forming DNA sequences. Efficient and specific target recovery was achieved using optimized buffer conditions and magnetic Ni-NTA beads, while quantification was realized by employing the enzyme-like properties of the G4/hemin complex. The assay was validated through HPLC analysis and adapted for a 96-well plate format. The results show that higher recovery can be achieved using His-Tag with Ni-NTA magnetic beads as compared to the more common biotin-streptavidin purification. The inclusion of the G4-ligand as an additional selectivity handle was shown to be beneficial for both recovery and selectivity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

G-quadruplexes (G4 s) are secondary, tetraplexed DNA structures abundant in non-coding regions of the genome, implicated in gene transcription processes and currently firmly recognised as important potential therapeutic targets. Given their affinity for human proteins, G4 structures are investigated as potential decoys and aptamers. However, G4 s tend to adopt different conformations depending on the exact environmental conditions, and often only one displays the specifically desired biological activity. Their less intensively studied counterparts, the elusive tetraplexed intercalated-motifs (IMs) are typically unstable at neutral pH, hampering the investigation of their potential involvement in a biological context. We herein report on a photochemical method for "stapling" such tetraplexed-structures, to increase their stability, lock their topology and enhance their enzymatic resistance, while maintaining biological activity. The chemical structure and topology of the stapled Thrombin Binding Aptamer (TBA) was spectroscopically characterised and rationalised in silico. The method was then extended to other biologically relevant G4- and IM-prone sequences, hinting towards potential application of such stapled structures in a therapeutic context., (© 2024 Wiley-VCH GmbH.)

The reuse of multilayered materials, which are held together by structural epoxy adhesives, is a major challenge since the bonded substrates cannot be easily separated for recycling. In this research, we explore a one-pot strategy based on β-amino ester chemistry for the development of modified epoxy adhesives with on-demand debonding potential. For this, a formulation of commercially available acrylate, epoxy and amine compounds is used. The research starts with a systematic study, demonstrating the influence of the different compounds on the thermal and adhesive properties of the materials. Subsequently, the potential for debonding is demonstrated using rheological measurements and tensile tests. The fast, catalyst-free Aza-Michael reaction enables the straightforward preparation of such epoxy-based adhesives, while the reverse reaction allows for debonding at 120 °C. In general, a chemical design is demonstrated for producing an industrially attractive generation of debondable epoxy-based adhesives.

Oriented cell divisions are crucial for determining the overall morphology and size of plants, but what controls the onset and duration of this process remains largely unknown. Here, we identified a small molecule that activates root apical meristem (RAM) expression of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE13 (SPL13) a known player in the shoot's juvenile-to-adult transition. This expression leads to oriented cell divisions in the RAM through SHORT ROOT (SHR) and cell cycle regulators. We further show that the RAM has distinct juvenile and adult phases typed by morphological and molecular characteristics and that SPL factors are crucially required for this transition in Arabidopsis and rice ( Oryza sativa ). In summary, we provide molecular insights into the age-dependent morphological changes occurring in the RAM during phase change.

Aromatic esters are amongst the oldest known chemical motifs that allow for thermal (re)processing of thermosetting polymers. Moreover, phenyl esters are generally known as activated esters that do not require a catalyst to undergo acyl transfer reactions. Even though dynamic aromatic esters find applications in commercialized thermoset formulations, all-aromatic esters have found limited use so far in the design of covalent adaptable networks (CAN) as a result of their high glass transition temperature (T g ) and specific curing process. Here, a strategy to include partly aromatic esters as dynamic cross-links inside low T g (-40 °C) thermosetting formulations, using aliphatic esters derived from para-hydroxybenzoic acid, which serves as a highly activated phenol or as a reactive "phenylogous anhydride" is reported. A small molecule study shows that the activated phenyl ester bonds can readily exchange with free phenol moieties at 200 °C under catalyst-free conditions, while the addition of a catalyst allows for a faster exchange. Robust and hydrophobic polymer networks are conveniently prepared via rapid thiol-ene UV-curing of unsaturated phenol esters. The obtained networks show high thermal stability (350 °C), fast processability, good water resistance, and low creep up to 120 °C, thus showing good promise as a platform for CAN., (© 2024 Wiley‐VCH GmbH.)

The automated elucidation of the interplay between monoclonal antibody (mAb) structure and function using two-dimensional liquid chromatography-mass spectrometry (2D-LC-MS) is reported. Charge variants, induced through forced degradation, are resolved by first-dimension ( 1 D) cation-exchange chromatography (CEX) and subsequently collected in loops installed on a multiple heart-cutting valve prior to transfer to second-dimension ( 2 D) neonatal crystallizable fragment receptor (FcRn) affinity chromatography coupled with MS. As such, binding affinity of the latter mAb variants can elegantly be assessed and a first glimpse of identity provided. To maximize MS sensitivity, charge variants are unfolded upon eluting from the 2 D affinity column by postcolumn addition of a denaturing solution. Further structural details, i.e., modification sites and chain distribution, are unraveled by a multidimensional LC-MS (mD-LC-MS) setup incorporating 1 D CEX and parallel online middle-up and bottom-up LC-MS analysis in the subsequent dimensions. Identified charge variants could be ranked according to their affinity for FcRn. Binding is predominantly impacted by heavy chain (HC) M 253 oxidation and to a lesser extend, M 429 oxidation. Oxidation of both HCs more drastically affects FcRn interaction compared to single-chain oxidation, and the more oxidation, the less binding. Other modifications, such as HC glycosylation, HC N 385/390 , and N 326 deamidation or HC C-terminal processing, are not shown to affect binding. The streamlined platform is challenged against the established workflow involving offline collection of charge variants and structural and functional assessment by, respectively, LC-MS and enzyme-linked immunosorbent assay (ELISA). A decent correlation is demonstrated between the binding affinity measured with ELISA and 2 D FcRn affinity chromatography. In addition, throughput is improved (7-fold), material requirements are substantially reduced (2 orders of magnitude), and sample preparation artifacts and loss are minimized. With the simultaneous determination of mAb structure and function, the current study takes the concept of multiattribute analysis to the next level, thereby contributing to the future development of safer and more effective antibody therapeutics.

The full potential of sequence-defined macromolecules remains unexplored, hindered by the difficulty of synthesizing sufficient amounts for the investigation of the properties of such uniform structures and their derived materials. Herein, we report the bidirectional synthesis and thermal behavior analysis of sequence-defined oligourethanes. The synthesis was conducted on a large scale (up to 50 grams) using a straightforward protocol, yielding uniform macromolecules as validated by NMR, ESI-MS and SEC. With this approach, a library of uniform oligourethanes (up to the octamers) was produced using two structural units: a hydrogen-bonding carbamate and a methyl-substituted alternative structure. By varying the chain length, monomer sequence and functionality, we were able to perform a systematic study of the impact of hydrogen bonding on the thermal properties of polyurethanes. Thermal analysis of the discrete oligomers using DSC revealed that both the molecular weight and microstructure significantly affect the glass transition and melting temperatures. TGA measurements also revealed differences in the thermal stability of the oligomers, underscoring the significance of the primary structure of polyurethanes. Additionally, the influence of the terminal groups on the degradation pathway was assessed via pyrolysis-GC-MS, which specifically highlighted the increased thermal stability in the absence of hydroxyl end groups. This work shows the interest of using sequence-defined synthetic macromolecules for the elucidation of structure-property relationships and thereby facilitates their fine-tuning towards specific material applications., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)