Recently, the hydrophilic corona of block copolymer micelles (BCMs) was shown to be of underappreciated importance for drug formulation.[1-2] More precisely, critical but previously ignored corona-drug interactions were demonstrated.[3-4]
Here, we introduce a small library of ABA-type triblocks with varying hydrophilic blocks for systematic investigations regarding the influence of the hydrophilic corona on the performance of BCMs as drug carriers. The synthesis of the copolymers was realized using a polymer-polymer coupling procedure based on copper-catalyzed azide-alkyne cycloaddition reaction.[5] As a central hydrophobic block, poly(2-butyl-2-oxazine) (PBuOzi) was used in all copolymers. For the flanking hydrophilic blocks, a set of well-studied stealth polymers was chosen including poly(2-methyl-2-oxazoline) (PMeOx), poly(N,N-dimethyl acrylamide) (PDMA), polysarcosine (PSar) and the gold standard polyethylene glycol (PEG), among others.
We tested the synthesized copolymers for their loading capabilities of the model drugs curcumin and indomethacin. In this respect, the variation of hydrophilic moieties was shown to have a notable impact on drug solubilization and formulation stability, corroborating previous, less extensive work. Further, we investigated a small selection of polymers for their interactions with the simulated intestinal fluid by ¹H NMR shift analysis and DOSY NMR measurements. The analysis revealed only minor differences in their interference with biorelevant media. Lastly, first in vitro endocytosis data of curcumin formulations are obtained to unravel the impact of the hydrophilic corona on cell internalization.

The NEXTSCREEN project aims to enhance imaging flow cytometry by developing innovative microfluidic tools that improve resolution, throughput, and cost-efficiency for single-cell analysis. The research also focuses on the synthesis and characterization of low-refractive-index polymers [1] optimized for microfluidic applications, these materials are designed to minimize optical aberrations that could interfere with imaging. A key objective is the development of scalable synthesis protocols using free radical and controlled radical polymerization [2], optimizing the optical, mechanical, and chemical properties of these polymers. The refractive index of these materials is tailored to match biological media (e.g., water, cell culture solutions), reducing light scattering and enhancing imaging resolution, in order to achieve this fluorinated materials are being investigated, as fluorine’s unique characteristics, such as low polarizability, contribute to a low refractive index in fluorine-containing compounds. Additionally, their chemical structure is designed to improve processability and compatibility with advanced fabrication techniques. is designed to improve processability and compatibility with advanced fabrication techniques. In this regards, two-photon polymerization (TPP) is being explored for precise microscale structuring [3], enabling the fabrication of complex yet optically clear and stable architectures. This research aims to advance optofluidic platforms for imaging and diagnostics, potentially offering an alternative to conventional materials like PDMS. Future efforts will focus on refining polymer formulations, optimizing fabrication methods, and evaluating their performance in prototype devices.

Porous polymer scaffolds play a crucial role in tissue engineering (TE) by favoring cell growth and restoration of tissue and organ function.[1] Key features of these scaffolds are biocompatibility, adjustable degradability, mechanical properties comparable to the native tissues, and controlled porosity to promote implant colonization, nutrient supply and waste elimination.[2] In this respect, polyphosphoesters (PPEs) appear as valuable candidates for TE applications, given their biocompatibility and tunability of their hydrophilicity and hydrolytic degradation through modification of their pendant groups.[3] This communication aims to report on the development of innovative degradable PPE-based porous scaffolds structured by high internal phase emulsion (HIPE) templating polymerization. For this purpose, novel degradable PPE-based surfactants were synthesized by sequential Ring Opening Polymerization (ROP) of cyclic phosphates and tested as alternative to the classical non-degradable surfactants for the stabilization of the HIPEs. Surface tension measurements confirmed the surface-active properties of these macromolecular surfactants, which were subsequently used to formulate a series of open-cell macroporous PPE-based scaffolds also called polyHIPEs. The impact of the structure and concentration of the surfactants on the morphological characteristics, mechanical properties, and degradability of these scaffolds will be discussed. Ultimately, adequate interconnected porous morphologies and degradability were achieved along with mechanical properties tailored for soft tissue engineering applications.

Biomaterials based on citric acid have shown potential to be used as tissue substitutes. The successful commercialisation of implants containing poly(octamethylene citrate) provides grounds for exploring polycitrates based on other diols. Changing the chain length of the diol allows functional design strategies to control the implant's mechanical and surface properties and its degradation profile.

The aim of this work was to obtain electrospun nonwovens by mixing PLA with different poly(diol citrates) to study how the diol chain length influences the material properties.

Poly(dimethylene citrate), poly(tetramethylene citrate) and poly(hexamethylene citrate) were synthesized and blended with PLA to produce nonwovens via electrospinning. The nonwovens were studied and characterized using various methods: SEM, AFM, water contact angle measurement, DSC, TGA, and degradation tests.

The materials appeared porous in structure with well-developed, evenly distributed fibres with no apparent structural defects. Surface properties were analysed on the basis of water contact angle and AFM imaging, which showed somewhat contrasting results. The surface character of this type of material can be classified variously, depending on the level (macro/micro) of determination. Nevertheless, the effect of adding poly(diol citrate) to fibre-forming PLA is evident and varies depending on the diol used.
However, studies have shown the problem of the incompatibility of polycitrates with PLA, which results in instability of the system in the aqueous medium and leaching of the oligomeric chains from the structure. The hydrolytic degradation of polyester nonwovens is relatively rarely reported in the literature but is a crucial issue in terms of their biomedical application.

Ibuprofen (IBU), a popular non-steroidal anti-inflammatory drug (NSAID), has low solubility in water and low bioavailability, thus requiring frequent administration. However, long-term use of IBU may have some serious side effects like hepatitis and strokes, so it is desirable to design controlled release systems and/or more bioavailable forms for the drug. For this purpose, we propose a hydrogel-based delivery system for IBU, with added desirable property of redox-responsiveness.
In this study, a novel disulfide and IBU-functionalized dimethacrylate crosslinker (IBU-SS-MA) is synthesized to fabricate said hydrogels. IBU-SS-MA was successfully synthesized in five steps: (i) synthesis of tert-butyl -hydroxymethacrylate from the reaction of tert-butyl acrylate and paraformaldehyde in the presence of 1,4-diazabicyclooctane, (ii) conversion to tert-butyl-bromomethacrylate (TBBr), (iii) nucleophilic substitution reaction of TBBr with IBU sodium salt, (iv) synthesis of methacrylic acid derivative by cleavage of tert-butyl groups and (v) condensation of the acid with 2-hydroxyethyl disulfide. The copolymerization reactivity of IBU-SS-MA with common hydrogel monomers, poly(ethylene glycol) diacrylate (PEGDA, Mn=575 D) and 2-hydroxyethyl methacrylate (HEMA), was investigated with photo-differential scanning calorimetry. Degradation of the PEGDA hydrogels upon exposure to glutathione confirms the redox-responsive behavior. The release of IBU from hydrogels is exceptionally slow, i.e. 50% in 40 days depending on their composition. These properties show that the synthesized hydrogels are promising candidates for alleviating problems of IBU while keeping the benefits.

The authors would like to acknowledge financial support from Bogazici University (BAP/ADP 50003).

To prolong usage and mitigate infections associated with bacterial colonization on medical catheters, development of water-dispersible polyurethane (PU) coatings with bactericidal properties is desirable. With this objective, we have formulated polyurethane coatings that exhibit both antibacterial activity and water dispersibility. A piperazine-based diol, 1,4-bis(2-hydroxyethyl)piperazine (HEPZ), was synthesized and used as a chain extender in PU synthesis. The PUs were prepared using hexamethylene diisocyanate (HDI), 4,4’-methylene diphenyl diisocyanate (MDI), polyethylene glycol (PEG600), and polypropylene glycol (PPG400), resulting in a series of polyurethanes (PU1-PU4). MDI-containing PUs showed superior tensile strength (3.2-3.6 MPa) and elongation (67-70%) attributable to their higher aromatic content. The PEG600-containing PUs (PU1 and PU3) were alkylated using methyl iodide (MeI) to varying degrees whereby a significant reduction in contact angle from ~82° to ~62° was observed, indicating enhanced hydrophilicity. MPU3-D with 72.5% methylation demonstrated the most stable water dispersion with a particle size of ~190.8 nm and a zeta potential of +49.0 mV. In vitro cytocompatibility studies further revealed that methylated PU3 exhibited higher compatibility (80-90%) compared to methylated PU1 (30-40%). Additionally, MPU3-D films also demonstrated antibacterial activity against gram-negative (E. coli) and gram-positive (S. aureus) bacteria, with zones of inhibition measuring 7 mm and 8 mm, respectively. Also, water-dispersible MPU3-D-based coating with hardness of ~75A and thickness of ~17 µm (as observed through FESEM) showed strong adhesion to PVC catheters, exhibiting an adhesion strength of 4B rating. Our results suggest that water-dispersible polyurethane coatings with antibacterial properties are promising materials to reduce catheter-associated infections and enhance patient care.

The growing demand for sustainable packaging solutions has led to a surge in interest in utilizing paper and other cellulose-based materials, as renewable and biodegradable alternatives to traditional plastics1. The packaging industry and manufacturers are investing in the development of high-performance materials and efficient strategies to produce paper and cellulose materials with notable barrier properties. These bio-based alternatives not only fulfill the functional requirements of packaging but also help minimizing environmental harm, thereby accelerating the shift toward a more sustainable future2. Among the available bio-based solutions, fatty acids, vegetable oils, and their derivatives have demonstrated considerable potential in enhancing the surface hydrophobicity of various materials while maintaining a minimal environmental footprint3.
The goal of this PhD project is to develop highly hydrophobic coatings made from sustainable building blocks, ensuring their easy application onto cellulose-based substrates using an industrial-scale machinery. The research project focuses on synthesizing innovative hydrophobizing additives used as coatings for cellulose substrates, derived from polyols, flavonoids, and fatty acids, all exhibiting strong hydrophobic properties. Different spectroscopic and thermal techniques have been carried out for structures and properties evaluation not only on pure products but also for studying chemical interactions (by Solid State-NMR) between them and the inorganic compound able to strongly enhance the hydrophobic properties (water contact angles > 140°). SEM images have shown the morphology of the different coatings applied around the cellulose fibers.
This all-encompassing approach underscores the technological and material progress achieved throughout the project, setting the stage for its future application on industrial scale.

The interest in silk fibroin hydrogels from Bombyx mori silkworms as versatile, highly biocompatible tough cheap raw material for applications especially in biomedical engineering was recently on the rise [1]. Regarding this, we investigated the physical chemistry of the shift of amide I Raman-spectral shifts indicating secondary structural changes with respect to congealing mechanism of the synthesised films, sponges and hydrogels. The congealing mechanisms used involved self-gelation, sonication, vortexing, film formation and sponge creation by the salt leaching method. Regarding the investigation of amide I shifts, peak deconvolution was employed. Subsequently, all resulting gels and derivates were loaded with calcium chloride and exposed to solutions of sodium carbonate to explore their capabilities of potential bio-mineralization [2]. The evaluation of bio-mineralization capabilities was performed by using confocal Raman-µ-spectroscopic imaging area and volume scans, with calcium carbonate used as a reference substance for True Component Analysis (TCA), a non-negative matrix factorisation dimensionality reduction algorithm creating spectral distribution images that can be rendered into 3D volume distributions. The highest intensity alteration after normalisation on the area of thev(C-H) vibration was found in the amide I vibration with the congealing mechanism of sonication. The strongest shift in normalised amide I peak was found in the samples prepared as film. Calcium carbonate was subsequently detected in all the specimens, with its most abundant appearance in the sponges. The aspect of simple aggregation or actual diffusion within the gel structure is still aspect of ongoing research.

Cancer treatments lack selective targeting of tumor cells, thus limiting therapeutic efficiency and causing undesirable side effects. Amphiphilic block copolymer micelles can encapsulate (protect) the drug and use a stealth polyethylene glycol (PEG) corona for longer circulation in blood.[1] Furthermore, their potentially pH-responsive character enables targeted release in tumor sites (pH~5-6). However, preparing pH-sensitive block copolymers is generally laborious, and PEG raises hypersensitivity concerns.[2]
In this context, we focus on new and easily achievable pH-sensitive block copolymer micelles for anticancer drug delivery. The approach is based on an hetero bi-functional pH-sensitive initiator, able to initiate both controlled radical polymerization (for the hydrophilic part) and ring opening polymerization (for the hydrophobic part, i.e. polylactide (PLA)). The pH-sensitivity is brought by an imine function, undergoing hydrolysis at acidic pH, thus allowing cleavage at block junction. The initiator was obtained in a 2 steps synthesis. The dual initiator was used for nitroxide mediated polymerization (NMP) of 4-acryloylmorpholine (NAM) at 100 °C and ring opening polymerization (ROP) of D,L-lactide at room temperature in presence of DBU catalyst. The PNAM-imine-PLA block copolymer formation was shown by 1H NMR and size exclusion chromatography (SEC). Micelles from the amphiphilic copolymers were prepared by the nanoprecipitation process. At physiological pH (7.4), micelles were about 100 nm in diameter and were stable. At tumor mimicking pH (5.5), micelles size increased over time, as a result of cleavage and formation of polymeric aggregates, demonstrating the relevance of our approach for triggering drug release in a cancer context.

Poly(3-hydroxybutyrate) (P3HB) is a polyhydroxyalkanoate biopolymer naturally synthesized by bacteria as a carbon and energy reserve. Despite its high crystallinity and production costs, P3HB exhibits piezoelectric behavior, making it promising for biomedical applications by providing mechanical or electrical stimuli.1
To overcome production constraints, the ring-opening polymerization (ROP) of rac-β-butyrolactone (BBL) using metal catalysts enables tailored P3HB synthesis.2 Aluminum-based catalysts are particularly advantageous due to aluminum’s abundance and cost-effectiveness, demonstrating strong ROP activity.3,4
Chitosan, a natural biopolymer, has gained attention in tissue engineering for its biocompatibility and antimicrobial properties. It also exhibits piezoelectric properties due to its non-centrosymmetric crystalline structure.5 However, its limited mechanical strength restricts its applications.
This study combines P3HB and chitosan to develop materials with enhanced mechanical properties for biomedical use. An aluminum complex with phenoxyimine ligands was employed to synthesize atactic P3HB with varying molecular weights via catalytic ROP of BBL. These biopolymers, along with chitosan, were blended with high-molecular-weight bacterial P3HB to improve material functionality.
Blends were processed via solvent casting and electrospinning, followed by morphological, thermal, and piezoelectric analyses to assess their structure and properties. A biological study using fibroblast cells evaluated the biocompatibility of each blend, highlighting the impact of processing methods on cellular interactions. These findings provide insights into the potential of P3HB-chitosan materials for biomedical applications.

Formation of bacterial biofilms poses a significant challenge for the healthcare due to the robust protective mechanisms of the bacteria, which are protected in the biofilm not only from the host’s immune system, but also from the antibiotic treatment. The formation of bacterial biofilms on the surfaces of implants, such as artificial joints and stents, is particularly problematic, as it often necessitates reoperations – procedures that can be life-threatening for elderly and/or critically ill patients. Our study [1] explored several innovative approaches to address this issue. The first one was based on the electrochemical generation of reactive oxygen species by the polytetrathienylporphyrin (poly-3TTP) metal complex layer at the surface of anode. The poly-3TTP/Fe demonstrated the highest catalytic activity of H₂O₂ generation, compared to complexes of poly-3TTP with other metals. The second approach was focused on the formation of bactericidal polycations from electrochemically oxidized layer of ferrocene polyamide. These polymers showed significant enhancement of electrochemically mediated eradication of Staphylococcus aureus biofilms.
Financial support to the project New Technologies for Translational Research in Pharmaceutical Sciences /NETPHARM, project ID CZ.02.01.01/00/22_008/0004607, co-funded by the European Union, is gratefully acknowledged.

Biopolymers, derived from renewable sources, have emerged as a sustainable alternative to traditional synthetic polymers. Due to particular properties, such as biocompatibility, biodegradability, non-toxicity, and functionality, they have become promising candidates for a wide range of applications, especially in the medical sector.
The study aims to develop and optimize an innovative hydrogel formulation based on gellan gum and carrageenan enriched with encapsulated thyme oil. The proposed formulation would become a substitute for traditional orthodontic wax. The resulting material could minimize contact of sharp, metal brackets with soft tissues of the oral cavity and protect micro-injuries. Moreover, hydrogel material would gain therapeutic properties by supplementing thyme essential oil to support oral hygiene. The development of this combination could enhance patients' comfort while wearing orthodontic appliances and complement the dental market.
However, dental biomaterials are required to deal with numerous adversities, like mechanical stresses, high humidity and acidic pH, and microbial contamination. This study highlights using atomic force microscopy (AFM) to measure surface roughness and determine the adhesion to the dental braces. Furthermore, the research focuses on the interactions between hydrogel formula and the harsh oral environment regarding swelling and sorption behavior under physiological conditions.

PEGylation, the covalent attachment of poly(ethylene glycol) (PEG) to active substances, can improve the pharmacological profile of therapeutics.¹ But besides the advantages of PEGylation, the presence and the emerging prevalence of anti-PEG antibodies is a great challenge, especially for repeatedly administered treatments for chronic diseases. 40% of patients show induction of anti-PEG antibodies after the treatment with PEGylated uricase (Krystexxa®), which is approved by the U.S. Food and Drug Administration for chronical gout therapy.² Furthermore, 50% of patients with high titers of anti-PEG antibodies prior to treatment show infusion reactions to the drug, of which 26% were categorized as severe and 6.5% as life threatening anaphylaxis.³

To overcome the challenge of anti-PEG antibodies, alternatives for PEG are investigated. We propose randomized PEG (rPEG), a structural isomer of PEG, which is synthesized by statistical anionic ring-opening polymerization of ethylene oxide and glycidyl methyl ether. rPEG shows reduced anti-PEG antibody recognition depending on the glycidyl methyl ether content.⁴ Based on these results, rPEGylated uricase seems promising to exhibit reduced immunogenic properties in comparison to the PEGylated analogue Krystexxa®. We demonstrate that rPEG₂₁₈ can be activated via p-nitrophenylchloroformate and unselectively conjugated to uricase analogously to PEG. Immunogenic properties and biocompatibility of the conjugate are currently investigated.

To date, polyacrylate, polylactide (PLA), and poly(ε-caprolactone)-based materials are most commonly used for 3D printing.[1,2] Those materials have significant advantages (biodegradability, biocompatibility for PLA and PCL, and good mechanical properties for acylate compounds). Nonetheless, they have some major disadvantages.[3] PLA and PCL are characterized by fragility and low cell adhesion (if we consider them for use in 3D bioprinting).[2] Furthermore, acrylate compounds are toxic and are usually obtained from non-renewable raw materials, which is against the trends of Green Chemistry. Thanks to the presence of multiple bonds in the structure of acrylate polymers, they can be subjected to UV light. It makes it possible to print a high-quality model of the desired shape successfully. 3D printing can also be used to obtain cellular scaffolds with applications in tissue engineering. For this, it is necessary to use non-toxic materials that have the potential to mimic the cellular matrix naturally found in the human body. In this research, aliphatic itaconic polyesters will be investigated. Itaconic compounds are structurally similar to acrylate ones.[4] A C=C bond in the structure of the itaconic compound allows UV-enhanced crosslinking. Itaconic compounds are fully biodegradable, biocompatible, and have anti-bacterial and anti-inflammatory properties.[5] The synthesis of itaconate-based polyesters was performed during the research. Based on the study's results, the product with the best properties was selected for UV-crosslinking, and the cured products were characterized in detail. In particular, mechanical, thermal, degradation, and cytotoxicity tests were carried out.

Among the biomaterials used in tissue engineering for scaffold development, polycaprolactone (PCL) stands out as a versatile, biodegradable synthetic polymer with good mechanical properties [1]. This work focuses on the fabrication of electrospun scaffolds from PCL combined with Kefiran, a natural biopolymer known for its high hydrophilicity, with the aim of improving material degradation and promoting cell adhesion in the tissue [2]. Calcium oxide nanoparticles (n-CaO) were incorporated due to their ability to stimulate the formation of hydroxyapatite (HA), a key component for bone tissue regeneration. The PCL/Kefiran/n-CaO scaffold presented homogeneous and defect-free fibers (Figure 1a). After immersing the scaffolds in simulated body fluid (SBF) solution, it was observed that the addition of n-CaO promoted HA formation on the scaffold surface, and the presence of Kefiran further enhanced this formation (Figure 1b). Moreover, the PCL/n-CaO and PCL/n-CaO-Kefiran scaffolds did not show cytotoxic effects on human osteosarcoma cells (MG-63), with a cell viability reduction of less than 30%, in accordance with ISO-10993-5 standards (Figure 1c). These results suggest that PCL/n-CaO and PCL/n-CaO-Kefiran scaffolds have great potential as devices for bone tissue regeneration.

Acknowledgments:
The authors would like to thank the FONDECYT Regular Project 1220093 and the ANID 2022 National Doctoral Grant (21221320).

Among numerous possible applications of elastomers, the biomedical field is one of the most demanding regarding mechanical properties. Indeed, depending on the targeted medical application, elastomers require different features such as toughness, extensibility but also degradability. Since the offer for non-toxic degradable elastomers is slim, new materials must be investigated in order to reach unmet needs. In that frame, polyphosphoesters constitute a rising class of degradable polymers, particularly promising for the biomedical field thanks to its demonstrated biocompatibility and degradability. This work aims to improve the extensibility of polyphosphoester networks in order to enrich the features this class of polymers can offer.

Starting from a theoretical model that predicts the mechanical properties of chemical networks, different synthetic strategies were conducted to provide enhanced elastomer properties to the materials. For that purpose, photocrosslinkable polyphosphate copolymers were synthesized by organocatalyzed ring opening polymerization (ROP) with different architectures. In this work we report the first polyphosphoester elastomer with a maximum elongation at break reaching 180% where the last published elongation did not exceed 15%. We further established relationships between the microstructure of the polymer chains and their mechanical properties, such as Young’s modulus and maximum elongation. These results pave the way for unprecedented biomedical applications of polyphosphoesters and reveal their high potential.

In situ forming implants (ISFI) offer the potential to avoid complications associated with the poor medication adherence. We have previously shown that the responsive nature of poly(N-isopropylacrylamide) (PNIPAM) nanogels have been used to trigger aggregation upon injection into physiological conditions form ISFI. These nanogel ISFIs have been combined with nanosuspensions of poorly water-soluble drugs to achieve long-acting release.1,2 However, one concern regarding PNIPAM is the nature of the acrylamide monomers used, therefore poly(oligoethylene glycol methyl ether methacrylate) (POEGMA) provides the alternative. Additionally, nanogels ISFIs have only been investigated for poorly-water soluble drugs. In this work, we present the development of POEGMA nanogels as ISFI, we also explore their potential for controlling the release of water-soluble compounds.

POEGMA nanogels were produced by dispersion polymerisation with the size of 85-183 nm. Rheological analysis revealed a transition in the POEGMA nanogel from liquid-like to gel-like behavior at ~24°C . The ability for the implants release model water-soluble compounds was then investigated on this with both small molecules and macromolecules, showing that charge interactions between the nanogels and the payload molecule would influence the release rate. These findings suggest that POEGMA nanogels provide promise as an ISFI for controlled release.