Technological advances in high performance polymers are significant, especially in processing thereof. Examples are scaffolds for regenerative medicine. Finding a balance between processability and polymer properties is a challenge. High-performance polymers' superior properties often come from the physical interaction between their polymer chains, which also cause the polymers' high melt and solution viscosity and low or non-solubility during processing creating challenges, which can be addressed with creativity and innovation. Recently, concepts for macromolecular metamorphosis of polymers during processing were introduced, improving the final material properties.
This contribution provides an overview of our approaches in this context to enhance the performance of materials for applications such as 3D-printed patient-specific implants or electrospun conduits as vascular replacement materials.
The initial example relates to self-reinforcing polyurethane ureas.[1] They transform when stored in water at moderate temperatures (e.g., body temperature). This creates stronger, more extensible polymeric materials. This process, contingent on the dynamic nature of hindered urea bonds (HUBs), has also been demonstrated applicable to polymeric networks, the foundation for vat polymerization 3D printing applications. Another example is the macromolecular metamorphosis of thermoplastic poly(thio)urethanes containing boronic acid esters.[2] Further concepts rely on the ring-opening during or after network formation, e.g., ring-opening of spirocyclic compounds, including spiro-ortho esters [3] and spiro-orthocarbonates [4], and radical-mediated redox rearrangements of cyclic benzylidene acetals.[5] These approaches specifically address the reduction of volumetric shrinkage during thermoset formation and connected warping during additive manufacturing, and the brittleness of the materials.

Polysaccharides represent the most abundant biopolymers. Among these, Pullulan, which can be produced from various carbon sources such as glucose, has garnered significant interest due to its biocompatibility, biodegradability, and non-toxicity. These properties make it suitable for diverse applications, including food, cosmetics, and biomedical [1]. However, modulating its inherent properties, such as water solubility, is essential for expanding its utility, especially in drug delivery systems. Fortunately, the hydroxyl groups on the pullulan backbone serve as reactive sites for chemical modifications, allowing the introduction of functional groups or polymers to create materials with enhanced properties. Concomitantly, stimuli-responsive polymers, particularly temperature-sensitive ones like poly (N-vinyl caprolactam), have garnered significant attention for their ability to change properties and release active compounds in response to environmental triggers. Notably, this polymer, exhibits a phase transition near physiological temperature, making it especially promising for drug delivery applications [2, 3].
In this work pullulan-graft-poly(N-vinyl caprolactam) (PULL-g-PNVCL) copolymers were successfully synthesized via controlled reversible addition-fragmentation chain transfer (RAFT) radical polymerization using xanthate as a chain transfer agent (CTA) to offer precise control over molar mass, molar mass distribution, and polymer architecture [4]. To that end, pullulan’s hydroxyl groups initially modified with 2-bromopropionyl bromide, forming bromide-functionalized pullulan. This intermediate was further substituted with a xanthate-based CTA, allowing NVCL polymerization from the pullulan backbone (Figure 1). The successful synthesis of pullulan-based (co)polymers was confirmed using gel permeation chromatography (GPC), Fourier-transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (¹H NMR), demonstrating polymer growth and specific functional groups incorporation.

An injectable surgical glue for local oxygen delivery has been developed to promote wound healing after esophageal surgery. The glue is formed through a Schiff’s base reaction by mixing chitosan and aldehyde-functionalized polycaprolactone (PCL) particles. The PCL particles were synthesized through a double emulsion¹ and functionalized in two sequential steps by incubating with hexamethylenediamine and terephthalaldehyde. This allows the addition of an amine group that was used to react with the aldehyde groups. Longer incubation times and higher temperatures during the functionalization enhanced the density of functional groups on the particle surface, leading to the formation of gels with increased crosslinking density. For instance, particles with a mean diameter of 87 μm functionalized for 3 and 10 min produced gels with stiffness of 50 and 150 Pa, respectively. Similarly, particles of 100 μm incubated with terephthalaldehyde at 38°C for 30 min and 39°C for 3 min resulted in hydrogels of 80 and 850 Pa.

This material was designed to prevent anastomotic leakage (AL), the most common postoperative complication in esophageal cancer patients. AL often results from reduced blood flow and oxygen concentration at the anastomosis site, impairing healing.² By providing localized oxygen delivery, this injectable adhesive aims to reduce AL risk and improve post-surgical outcomes. Future work will focus on optimizing the mechanical and adhesive properties of the system to ensure its suitability for clinical use, positioning it as a promising material for esophageal wound healing.

Increasing the size of polypeptide-drug conjugates (PDCs) by supramolecular assembly¹ or charge-like self-assembly² is an approach used to increase the half-lives and passive accumulation at pathological sites; however, the complexity of such crosslinked systems impedes the conventional method such as dynamic light scattering (DLS) to perform an exhaustive physico-chemical characterization. In response, we suggest the use of multimodal analytical platform that will elucidate better the biological fate of crosslinked polypeptide-based nanoconjugates.
We implemented design of experiment (DoE), a quality-by-design approach, for the design of genipin-crosslinked star-shaped polyglutamic acid-based combination nanoconjugates (GenXNanoComb) by implementing two strategies: 1) conjugation of drug combinations on the genipin-crosslinked nanocarrier surface and 2) crosslinking two single PDCs at a selected ratio. Additionally, a multimodal characterization platform, including DLS, fluorimetry, size exclusion chromatography and field flow fractionation coupled with advanced detection, and SAXS, was implemented to identify experimental factors influencing physicochemical attributes of GenXNanoComb.
DoE and multimodal characterization platform demonstrated that nanocarrier/PDC concentration, genipin equivalence, and interactions between nanocarrier/PDC concentration and ionic strength represent statistically significant factors impacting crosslinking. Following the second strategy, we discovered that a higher content of hydrophobic drugs in GenXNanoComb prompts the formation of more compact particles thanks to hydrophobic drug shielding in the nanoparticle core (only at low ionic strength).
We established a tailor-made DoE-assisted genipin crosslinking method for the design of GenXNanoComb for breast cancer treatment. Moreover, we illustrated how DoE combined with multimodal analytical platform provides a detailed picture of the behaviour of a given synthetic process with high efficiency.

Selective cell separation enabled by tailored cell release surfaces has shown great potential as promising cell separation technique for versatile applications in immunotherapy as well as in cell engineering, analysis and therapy. [1-4] Here we present a highly reproducible grafting-from approach, realised through a surface-initiated atom transfer radical polymerisation (SI-ATRP) of thermoresponsive poly (di (ethylene glycol) methyl ether methacrylate) (PDEGMA), affording polymer brushes, with dry thicknesses of 5 and 20 nm, respectively. Additionally, a diblock copolymer system, featuring an ultrathin 1 to 2 nm poly (glycidyl methacrylate) (PGMA) block on top of PDEGMA (PDEGMA-b-PGMA), was introduced to increase the number of functional groups due to the reactive epoxy-functionality within the side chain. Subsequently, a well-established and highly selective copper-catalysed alkyne-azide cycloaddition (CuAAC) was utilised to synthesize different end-group functionalised PDEGMA and PDEGMA-b-PGMA brushes through an azide intermediate. Results of the various end-groups and their effects on cell attachment, spreading, proliferation and apoptosis, after a 24 h incubation period under standard conditions (37 °C and 5% CO₂), and detachment upon a decrease in temperature to 20 °C will be discussed. In this context, we aim to refine, enhance and optimise the PDEGMA brush-based cell separation approach for divergent cell lines.