Introduction

In tissue engineering applications, studies generally focus on the rate of polymeric scaffold degradation in an aqueous or cell-medium environment. Our Unit has developed a poly(ester-urethane) (PEU) elastomeric scaffod for tissue engineering applications ([1-3]) and recently observed that, after being stored at room temperature for 4 years, fibroblast cells still adhere and proliferate significantly on the aged scaffold, but stay round all over the pore surface. The aim of this study is to explore how thermally accelerated aging of PEU scaffolds impacts on the cell response.

Methodology

PEU scaffolds were thermally aged from 7 to 50 days at 75°C and 90°C and characterized through microscopy, FTIR spectroscopy, colorimetric analysis and Brillouin spectroscopy.
For in vitro study, contact cytotoxicity as well as fibroblast adhesion, spreading and proliferation were evaluated.

Results

After aging, no modification of the porosity and the pore size were observed. The FTIR analysis did not shown any differences in the chemical structure. However, the scaffold yellowish aspect increased with the aging time. Brillouin scattering results show that the frequency shift is a function of aging time. The same observation is found for the width at half-height. Moreover, these variations are more important when the aging temperature is enhanced.
First contact cytotoxicity studies demonstrated that cells are affected after 3 days of contact with the aged scaffolds but tend to spread again after 7 days. Proliferation study is currently under investigation.

Figure : Colorimetric analysis (A) and Brillouin scattering (B) of the scaffold aged at 75°C

The widespread use of sensors is contributing to increasing e-waste, which is expected to reach 110 million tons annually by 2050 [1]. Sustainable sensors are urgently needed, particularly in agriculture, environment, medicine and in several industrial sectors [2-4]. Our approach replaces fossil-based, non-biodegradable materials with commercially available, biobased, and biodegradable alternatives by developing a gelatin-based sensor for monitoring to measure strain, temperature, and relative humidity.

The sensor (Fig. 1) consists of polylactic acid (PLA) as a substrate, on which electronic components are printed to amplify and transmit the measured electrical resistance. A sensitive layer made from gelatin with tannic acid (crosslinker), glycerol (plasticiser) and carbon black (conductive additive) is deposited on the PLA. To enhance the adhesion between the substrate and the sensitive layer, the surface of PLA is activated by e-beam irradiation, followed by grafting with hydroxyethyl methacrylate. The grafted surface showed reduced polar and increased dispersive fractions of the surface energy. Consequently, enhanced dispersive interactions between the sensitive layer and the PLA film forced improved adhesion of the layered structure, which was examined by cross-cut tests according to EN ISO 16276-2.

The electrical resistance was measured as a function of bending, temperature and humidity. Resistance changes to strain are observed in the range of ~ 2.7 Ω/N (3-point bending test), to temperature in the range of ~ 5 Ω/K (temperature test) and to humidity in the range of ~0.13 Ω/ppm (humidity test). Our results show that it is possible to construct these sensors using mainly biobased, biodegradable materials.

Stimuli-responsive polymeric nanoparticles that respond to the distinct microenvironment around tumor cells such as low extracellular pH, and high levels of glutathione, can provide precise and targeted release of drugs and minimize their non-specific accumulation in healthy organs. A pH and redox dual-responsive diblock copolymer POD-b-PDMAEMA-Q was prepared based on poly(1,4,5-oxadithiepan-2-one) (POD) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA). First, the POD block was prepared by the ring-opening polymerization of the disulfide-containing cyclic lactone, 1,4,5-oxadithiepan-2-one. Then, POD-b-PDMAEMA was synthesized by atom transfer radical polymerization of DMAEMA using hydroxyl terminated POD-OH as the macroinitiator. POD-b-PDMAEMA was quaternized with bromoacetic acid to prepare POD-b-PDMAEMA-Q. The particle size of the resulting self-assembled block copolymeric micelles was found to be in the 137-182 nm range with spherical morphology in aqueous solution. The POD-b-PDMAEMA-Q was converted to its polyzwitterionic form POD-b-PDMAEMA-ZIP in PBS (pH=7.4) buffer and then DOX was loaded within the polyzwitterionic micelle. The drug loading efficiency of copolymeric micelles was in the 32-51% range and showed 93-99% cumulative drug release at pH 6.5 in the presence of 2 mM dithiothreitol. The DOX-loaded copolymeric micelles effectively increased selective cellular uptake and cytotoxicity in 4T1 breast cancer cells while maintaining cytocompatibility in NIH-3T3 fibroblasts with lower cellular uptake. The BSA protein adsorption on the polyzwitterionic micelles was very low. Our results show that these disulfide-based dual-responsive polyzwitterionic nanoparticles show promise for targeted delivery of antitumor drugs while minimizing adverse effects on normal tissues and warrant further investigation.

Urea is widely used in various fields, including agriculture, dairy products, and food preservation, making its detection highly significant. Moreover, it serves as a crucial biomarker for assessing kidney and liver dysfunction [1]. In the dairy industry, urea is used as an additive to maintain the viscosity and consistency of milk. Elevated urea levels in the blood indicate kidney failure and gastrointestinal disorders, while decreased levels are associated with liver failure. The accurate determination of urea concentration plays a vital role in diagnosing kidney and liver diseases. Additionally, urea is extensively applied as a fertilizer in agriculture and as a stabilizer in soaps and detergents. However, excessive and prolonged use of urea leads to environmental issues such as soil acidification, eutrophication, aquatic life extinction, and acute poisoning in animals [2].
In this study, a novel ferrocene-appended conductive carbazole polymer was synthesized and used to modify a glassy carbon electrode (GCE) for the development of a urease-based bio-electrochemical sensor. Due to the synergistic effect of the polymer and the electrochemical properties of ferrocene, the sensor exhibited excellent performance in urea detection through voltametric measurements. The results demonstrated high sensitivity and selectivity, highlighting the potential of this polymer-based electrode for biomedical and environmental applications

Thiolated chitosans (Chit-SH) are biopolymers derived from chitin, found in the exoskeletons of crustaceans, insect cuticles, and algae. These polymers are modified by coupling thiol-functional reagents to their primary amino groups. Chit-SH offers a broad range of beneficial properties for biomedical applications, including biocompatibility, mucoadhesion, and wound healing (1). Additionally, Chit-SH can be integrated into nanosystems for the selective detection and treatment of tumors (2). This study focuses on large-scale synthesis of Chit-SH and its application as a capping agent for gold nanorods (GNRs), an optically active class of nanomaterials absorbing light in the so-called “biologicl window” (3). The system was further functionalized with an anti-integrin α5β1 aptamer, capable of selectively targeting bladder cancer cells smaller than 1 mm. The resulting chitosan-coated gold nanorods functionalized with the aptamer (GNRs@Chit-Apt) were synthesized and characterized. Critical process parameters influencing the synthesis were analyzed, including the degree of functionalization, the amount of Chit-SH used for capping, and the removal of cytotoxic CTAB from the GNRs. Additionally, the scalability and purification methods were optimized for large-scale production. The theranostic potential of GNRs@Chit-Apt was evaluated in preclinical trials, demonstrating its efficacy in targeting bladder cancer cells. These findings highlight the potential of Chit-SH as a versatile material for developing theranostic nanomaterials with applications in cancer detection and therapy.

Polymer lipids (PLs) are essential components of liposomes and lipid nanoparticles (LNPs) for drug and gene delivery, providing colloidal stabilization and defining the biological interface. While poly(ethylene glycol) (PEG)-based PLs are the current standard, they are suspected to be responsible for rare adverse reactions, e. g. to LNP-based Covid-19 vaccines.[1] Therefore, PLs based on alternative stealth polymers, such as Poly(2-ethyl-2-oxazoline)[2] or Poly(sarcosine)[3], are being intensively investigated for their use in LNPs. However, these alternative PLs often lack comparability due to different synthesis protocols and are not easily accessible. In this work, we present a catalyst-free, efficient and versatile coupling procedure for PL synthesis based on azide-functionalized polymers and electron-deficient acetylene dicarboxylate lipids (ADC Lipids). This approach allows to obtain comparable PLs comprising an identical triazole linker. To highlight the versatility, we prepared PLs based on PEG and 4 alternative stealth polymers with quantitative coupling efficiencies. The introduced linker structure showed appropriate cytocompatibility, biocompatibility and pH stability. In addition, all PLs enabled the preparation of well-defined liposomes with excellent stability. Taken together, our facile and versatile approach yields comparable PLs with minimized linker size, that are promising candidates for future comparative studies and biomedical applications.

The self-assembly of block copolymers has been widely explored as a platform for drug delivery applications, while the incorporation of stimuli-responsive segments into these polymers has been employed to enable precise spatial and temporal control over drug release.¹ Among various stimuli, temperature has gained significant attention, particularly in polymers exhibiting lower critical solution temperature (LCST) which facilitates the development of thermo-responsive self-assembled nanostructures.² However, polymers with an upper critical solution temperature (UCST) under physiological conditions have been far less studied, with most reports on their self-assembly in solution focusing on micellar morphologies for the controlled delivery of hydrophobic drugs.³ Herein, we report the development of vesicular nanostructures from block copolymers composed of a poly(ethylene glycol) hydrophilic block and a UCST block of poly(acrylamide-co-acrylonitrile). By judiciously adjusting the block copolymer composition and self-assembly conditions, we obtained vesicles with tunable size and sharp phase transitions in aqueous media. Below the UCST, these vesicles effectively encapsulated hydrophilic model dyes, while heating above the UCST induced their disassembly into hydrophilic polymeric chains, triggering dye release. We anticipate that these nanostructures will serve as a versatile platform for the controlled delivery of therapeutic drugs for applications in human medicine, livestock, and aquaculture.

KEYWORDS: drug delivery, thermo-responsive polymers, vesicles

ACKNOWLEDGMENTS
The research project was supported by the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “2nd Call for H.F.R.I. Research Projects to support Faculty Members & Researchers” (Project Number: HFRI-FM17-3346).

Polyunsaturated fatty acids (PUFAs) possess diverse important physiological functions, including brain development and diabetes prevention [1]. However, their efficacy is often compromised due to their susceptibility to oxidation and poor bioavailability. Amylose is widely used to construct drug delivery systems such as amylose-fatty acid complexes [2]. Understanding the mechanisms governing the self-assembly behavior of amylose and PUFAs is imperative for predicting the properties of these complexes and their stability. Some factors, such as amylose chain length, that affect complex properties have been reported [3]. However, how complexation temperature impacts the supramolecular assembly of amylose with PUFAs remains unclear. This study examined the effect of complexation temperature on the multiscale structure of amylose‒α‒linolenic acid (ALA) complexes. Amylose, obtained by debranching waxy maize starch, was complexed with ALA at temperatures of 30/50/70/90 °C. The solid-state nuclear magnetic resonance results indicated an increase in the single-helix content and a decrease in the double-helix content with complexation temperature reduced. At 30 °C, the complex presented the highest complexation rate (over 56%), smallest particle size (0.57 μm), optimal emulsion stability (zeta potential of -38.87), and highest melting temperature (83.13 °C). Molecular dynamics simulations further revealed that single helices can form at 30 °C and 90 °C and that elevated temperatures intensify both amylose‒amylose and amylose‒ALA interactions. Notably, the enhancement of amylose‒amylose interactions is approximately 3.7 times greater than that of amylose‒ALA interactions. These findings confirm the hypothesis that the complexation temperature is crucial in controlling the single/double helical structures and complexation rates of amylose-ALA complexes.

This study aims to connect piezoionics and muscle tissue engineering, exploring hydrogel applications in ionic environments and their effects on cellular behaviour in muscle regeneration. Muscle tissue engineering aims to create functional constructs for damaged tissues, often mimicking natural tissue properties like conductivity.[1] Traditional methods using metallic and carbon particles pose challenges such as inhomogeneity, manufacturing issues, and toxicity.
This work employs ion transport for precise control of hydrogel properties, avoiding particles to increase conductivity. Additionally, it explores the piezoionic potential of ionic hydrogels, which generate electricity through mechanical deformation, holding promise in tissue engineering. [2]
Novel RAFT copolymers were developed using neutral, cationic, and thiolated monomers, allowing independent tuning of crosslinking and charge density. Cationic photo-crosslinkable RAFT polymers were synthesized and used as thiol crosslinkers for gelatin-norbornene, forming hybrid ionic hydrogels upon photo-crosslinking. By varying the neutral:cationic:thiol ratio, crosslinking and charge density can be independently tuned. The hydrogels' storage/loss modulus, mass swelling ratio, gel point, and gel fraction were characterized.
At constant crosslinking density, the storage modulus remained unchanged, but swelling decreased significantly with increasing cationic charge density. Adjusting the thiol content allowed fine-tuning the storage moduli, while modifying the cationic content altered the mass swelling ratio. All gel fractions exceeded 95%, indicating efficient crosslinking due to the thiol-ene photo-crosslinking mechanism.
This three-component RAFT copolymer approach allows independent control of charge and crosslinking density, offering new insights into ionic conductivity and piezoionic potential in hydrogels, advancing muscle tissue engineering.

Invisible orthodontics (IO) is a novel orthodontic technique based on the preform of the patient's dentition with a slight misalignment that drives the tooth to its position. The preforms are manufactured using flat-extruded sheets of invisible thermoplastics shaped by thermoforming and laser cutting. [1]
The viscoelastic features of the chosen thermoplastic and the experience of the professional performing the treatment, rule not only the efficiency but also the pain and comfortability during the whole treatment[2], [3]Thus, too stiff materials can be disastrous in the wrong hands, while soft plastics would have a negligible effect on dentition. Hence, viscous properties are essential in how the stress decays over time. [4], [5]
Accuracy in manufacturing has also huge implications in treatment since it assures that the forces are the ones prescribed at each point. Thus, it is essential to easily shape the thermoplastic, seen as a low characteristic time, but the process of tooth moving requires the opposite. [3]
Our study aims to settle a relationship between properties in the time domain, such as stress relaxation and elasticity, and those in the frequency domain obtained by stretching and analyse the importance of those properties in an IO treatment.
Project funded by the Comunity of Madrid (Spain) regional government (IND2022/IND-23679) in IMDEA materials in collaboration with Secre Aligner S.L.

Poly(ethylene glycol) (PEG) is an essential building block in modern nanomedical applications. Poloxamers are one of the most frequently used PEG-based pharmaceuticals.1 However, a significant prevalence of anti-PEG antibodies (APAs) up to 83 % has been documented.2 Accelerated blood clearance (ABC effect) and complement activated-related pseudoallergy (CARPA) poses a serious risk for patients treated with PEG-based nanoformulations.3 Extensive research on PEG alternatives has been ongoing.4
As a novel approach, we have already presented the non-antigenic randomizedPEG (rPEG) technology, which preserves the fundamental polyether class while ‘mutating’ the architecture of the polymer chain. This is achieved via truly random copolymerization of ethylene oxide (EO) and glycidyl methyl ether (GME).5
In this study, we aimed to develop a fully polyether-based ABA triblock copolymer system utilizing rPEG as a non-antigenic, hydrophilic A-block and poly(anisyl glycidyl ether) (P(AnisylGE)) as the hydrophobic B-block. Anisyl glycidyl ether (AnisylGE) was chosen for the B-block due to its potential to enhance drug loading through increased hydrogen bonding, hydrophobic interactions, and π-π interactions.
The ABA triblock copolymers were synthesized using living anionic ring-opening polymerization (AROP) in a two-step, one-pot reaction. The resulting rPEG-b-P(AnisylGE)-b-rPEG copolymers were employed to solubilize curcumin via the thin-film method. Dynamic light scattering (DLS) analysis indicated the formation of spherical micelles in both empty and drug-loaded formulations. However, instability in curcumin-loaded micelles was observed, highlighting the need for further optimization.
In conclusion, the rPEG-b-P(AnisylGE)-b-rPEG copolymers successfully demonstrate the potential of this fully polyether-based system for drug delivery applications, though improvements in micelle stability are necessary.

Among anticancer therapies, photodynamic therapy (PDT) is an advantageous approach thanks to its noninvasive character and low side effects. Its principle is based on using a photosensitizer, light and presence of oxygen to generate singlet oxygen leading to cell death. However, common photosensitizers still lack tumor targeting properties as well as prolonged blood circulation. An example of such photosensitizer is protoporphyrin IX (PPIX), which is often administered not itself, but in form of a prodrug, 5-aminolevulinic acid (5-ALA), which is metabolized to PPIX inside the cells (1). To overcome the poor pharmacokinetics of 5-ALA, we designed new nanomedicines based on covalently conjugated 5-ALA or its hexylester (HAL) to a water soluble copolymer of poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA). Water soluble polymer conjugates based on PHPMA have been used successfully for the delivery of many anticancer agents (2) relying on the enhanced permeability and retention (EPR) effect enabling high accumulation of the polymer conjugate in the tumor tissue. Herein, we present the synthesis of the nanomedicines by controlled radical polymerization with subsequent conjugation of 5-ALA/HAL via a pH sensitive hydrazone bond. Such nanomedicines present desired physico-chemical properties, pH sensitive release of 5-ALA/HAL and superior anticancer efficacy in vivo after irradiation.

Sustainable agriculture requires precision herbicide delivery systems to minimize environmental impact while ensuring prolonged efficacy. Here, we report the fabrication of biodegradable poly(lactic acid) (PLA) hollow microparticles encapsulating atrazine, developed via a single-step solvent evaporation method. Ethylene-vinyl acetate (EVA) was used as a sacrificial core template to control shell thickness, yielding microparticles (200–300 µm) with tunable release properties. The core-shell structure was confirmed by scanning electron microscopy, with shell thickness easily adjustable by varying the polymer ratio. Raman spectroscopy verified atrazine encapsulation and selective EVA removal. The microparticles exhibited core-shell thicknesses ranging from 20–90 µm, tailored through formulation parameters. Encapsulation efficiencies remained high (~70–75%) before and after core dissolution. Optimizing the solvent ratio mitigated atrazine crystallization, ensuring uniform particle morphology.
In vitro release studies demonstrated that increased shell thickness significantly prolonged atrazine release. Greenhouse experiments showed that microparticle formulations (ATZP series) sustained target weed (mustard) suppression for over 45 days without reapplication, whereas commercial atrazine formulations (ATZ series) lost effectiveness after ~20 days. Studies also revealed that atrazine-loaded microparticles (ATZP), equivalent to commercial powder (ATZ), exhibited superior weed control while reducing active ingredient loss and maintaining efficacy. Control groups (no atrazine, empty particles) confirmed the controlled release effect.
This study highlights the potential of biodegradable PLA microparticles for prolonged herbicide release, reducing chemical input and enhancing weed control efficiency in sustainable agriculture.

Messenger RNA (mRNA) has emerged as a transformative therapeutic platform for disease prevention and treatment. The success of mRNA-based therapies in vivo depends on the development of delivery systems that are safe, effective, stable, and capable of protecting mRNA from degradation while ensuring efficient cellular uptake and release. Lipid nanoparticles (LNPs) have demonstrated clinical success as mRNA delivery vehicles, as exemplified by their pivotal role in mRNA-based COVID-19 vaccines. NGP Polymers, a start-up company from the University of Jena, is advancing the field through the development, scale-up, certification, and qualification of innovative polyoxazoline (POx)-based lipids and other POx-based excipients. Our research focuses on developing POx-based alternatives to PEG-lipids, with the goal of improving the efficacy and stability of mRNA delivery systems. Key aspects of our work include the development of robust analytical methods and the synthesis of POx with high α- and ω-end-group fidelity and purity, as well as low dispersity, enabling precise control over material properties for optimized performance and authorization in the pharma industry.

In 2023 malaria caused an estimated amount of 597 000 deaths.[1] To treat this deadly tropical disease, the World Health Organization (WHO) recommends the use of Artemisinin(-derivatives) in combination with at least one other drug to avoid resistances. In severe malaria, i.v. Artesunate (ARS) is the state-of-the-art treatment. However, even with hospital treatment, the mortality of severe malaria is still 10-20 %.[2] Therefore improved therapeutics for such cases are still required.
Drawbacks of ARS, such as low solubility at neutral pH or low circulation times might be improved upon by polymer conjugation. ISMAIL et al. showed that conjugates of Heparin and ARS can be used as an injectable formulation with improved plasma circulation time.[3]
The goal of this work was to synthesize conjugates of Poly(2-oxazoline)s (POx) and ARS with higher drug loading and increased drug solubility compared to previous systems. POx can be synthesized to well defined structures (low Dispersities) with versatile architectures and higher variability of their chemical composition than the natural polymer Heparin. On top of this, they can also offer high biocompatibility and stealth properties.[4] A variety of different OH-functionalized POx were synthesized with varying block copolymer structures and amphiphilicities. Polymer-drug-conjugations were carried out under mild conditions. Resulting conjugates had reproducible and high drug loading and were able to increase the water solubility of bound ARS.

Synthetic porous scaffolds play a pivotal role in tissue engineering (TE), providing structural support for cell growth and tissue regeneration. These scaffolds must exhibit controlled porosity to enable cell colonization and nutrient diffusion, along with a biodegradation rate synchronized with tissue development. While biodegradable polyester scaffolds are commonly used in TE, they are predominantly hydrophobic and designed for applications involving semi-rigid to hard tissues. This communication aims to report on the development of innovative degradable macroporous scaffolds made from polyphosphoesters (PPEs), a versatile class of degradable polymers with tunable physicochemical properties, which broadens the scope of TE. For the first time, PPE hydrogels were structured into 3D scaffolds using high internal phase emulsion templating, producing hydrophilic matrices with adjustable porosity and Young’s modulus tailored for soft tissue applications. Progressive scaffold biodegradation was validated at physiological pH. Biocompatibility was confirmed through indirect and direct toxicity assessments, showing excellent cell viability, while RGD functionalization enhanced cell adhesion. In vivo studies involving subcutaneous implantation in mice revealed effective scaffold colonization, minimal inflammation, and angiogenesis, supported by histological analysis. These findings emphasize the potential of PPE scaffolds for regenerative medicine applications.

One of the major challenges for modern implantology is the avoidance of implant failure and minimization of revisions and follow-up procedures for patients. For successful implant integration without future adverse effects, bacterial colonization of the implant-tissue-interface and the formation of a biofilm specifically needs to be avoided. [1,2]

One way of resolving this issue is the utilization of quaternized ammonium cations (QACs) on the surface that exhibit bacteria killing properties. [3] Once the bacteria have been killed however, bacterial debris piles up on the charged surface; effectively rendering the surface incapable of fulfilling its purpose for extended periods of time which is an issue in implantology. [4] Making use of zwitterionic moieties within the same active surface introduces a possibility to get rid of such debris due to its inherent anti-fouling properties. [5] Depending on the salt concentration of the environment, either the cationic or the zwitterionic portion of the compound becomes active (Fig. 1). Moreover, making use of the high biocompatibility of a hydrogel should greatly improve its performance in real-world applications.

So for this work, the synthesis and characterization of such switchable polyelectrolyte compounds is being carried out as well as their integration into a polymeric backbone, giving access to simple, dip-coatable network precursors that yield their respective hydrogels by UV-irradiation. Additionally, monomers with varying spacer lengths have been synthesized to alter the amphiphilic balance and directly influence the antibacterial activity.