Covalent Adaptable Networks Using ß-Amino Esters as Thermally Reversible Building Blocks.

In this study, ß-amino esters, prepared by the aza-Michael addition of an amine to an acrylate moiety, are investigated as building blocks for the formation of dynamic covalent networks. While such amino esters are usually considered as thermally nondynamic adducts, the kinetic model studies presented here show that dynamic covalent exchange occurs via both dynamic aza-Michael reaction and catalyst-free transesterification. This knowledge is transferred to create ß-amino ester-based covalent adaptable networks (CANs) with coexisting dissociative and associative covalent dynamic exchange reactions. The ease, robustness, and versatility of this chemistry are demonstrated by using a variety of readily available multifunctional acrylates and amines. The presented CANs are reprocessed via either a dynamic aza-Michael reaction or a catalyst-free transesterification in the presence of hydroxyl moieties. This results in reprocessable, densely cross-linked materials with a glass transition temperature (Tg) ranging from -60 to 90 °C. Moreover, even for the low Tg materials, a high creep resistance was demonstrated at elevated temperatures up to 80 °C. When additional ß-hydroxyl group-containing building blocks are applied during the network design, an enhanced neighboring group participation effect allows reprocessing of materials up to 10 times at 150 °C within 30 min while maintaining their material properties.

Surface Modification of (Non)-Fluorinated Vitrimers through Dynamic Transamination.

Surface modifications are typically permanent in shape and chemistry. Herein, vinylogous urethane (VU) chemistry is presented as an easily accessible and versatile platform for rapid, facile, and reworkable surface modification. It is demonstrated that both physical and chemical post-modification of permanent, yet dynamic elastic polymer networks are achieved. Surface patterns with high regularity are created, both via a straightforward replication process using a polydimethylsiloxane stamp (resolution ca. 10-100 µm) as well as using thermally activated nano-imprint lithography (NIL) to form hole, pillar, or line patterns (ca. 300 nm) in elastic VU-based vitrimers. The tunable, rapid exchange allows patterning at 130 °C in less than 15 min, resulting in an increased water contact angle and surface-structure induced light reflection. Moreover, it is also demonstrated that the use of a single dynamic covalent chemistry makes it possible to strongly adhere to fluorinated and non-fluorinated materials based on incompatible matrices, causing cohesive failure in a peel test. In a topography scan, the visibly transparent interface is shown to possess a continuous phase without a gap, while maintaining distinctively separated (non)-fluorinated domains. Finally, this approach allowed for a straightforward coating of a non-fluorinated material with a fluorinated monomer to minimize the overall fluorinated content.

Fluorinated Vitrimer Elastomers with a Dual Temperature Response.

Vitrimers are an emerging new class of permanently cross-linked polymeric materials that show a liquid behavior upon heating wherein the macroscopic deformation is controlled by the rate of internal chemical bond exchange reactions. Thus, quite uniquely among polymeric materials, flow rates and material viscosities can be enhanced or controlled by the addition of catalysts and additives. We now report a catalyst-free vitrimer system, prepared from mixing two simple components, wherein two competing bond exchange mechanisms coexist, each showing a strikingly different temperature dependence, related to the large difference in activation energy for the different exchange pathways (60 vs 130-170 kJ/mol). The low barrier process is predominant at lower temperatures, but is outcompeted by the high barrier process that becomes dominant at higher temperatures because of its much more pronounced temperature dependence. The result is an interesting and highly unusual dual viscosity profile for this new class of vitrimer materials: a very gradual decrease in viscosity at lower temperatures, intercepted by a much sharper drop in viscosity at higher temperatures. The highly counterintuitive effect where a higher barrier pathway is dominant over a much lower barrier process can be rationalized by the exchange mechanisms that involve different reactive species, but lead to the overall same exchange. We observed this unusual but highly promising behavior first for fluorinated vitrimer elastomers, aimed at high performance materials, but the effect was also shown to hold in related nonfluorinated elastomers. A new way to control and design the rheological behavior of vitrimers toward finely tuned and precisely controlled processing applications has thus been provided.

Vitrimers: directing chemical reactivity to control material properties.

The development of more sustainable materials with a prolonged useful lifetime is a key requirement for a transition towards a more circular economy. However, polymer materials that are long-lasting and highly durable also tend to have a limited application potential for re-use. This is because such materials derive their durable properties from a high degree of chemical connectivity, resulting in rigid meshes or networks of polymer chains with a high intrinsic resistance to deformation. Once such polymers are fully synthesised, thermal (re)processing becomes hard (or impossible) to achieve without damaging the degree of chemical connectivity, and most recycling options quickly lead to a drop or even loss of material properties. In this context, both academic and industrial researchers have taken a keen interest in materials design that combines high degrees of chemical connectivity with an improved thermal (re)processability, mediated through a dynamic exchange reaction of covalent bonds. In particular vitrimer materials offer a promising concept because they completely maintain their degree of chemical connectivity at all times, yet can show a clear thermally driven plasticity and liquid behavior, enabled through rapid bond rearrangement reactions within the network. In the past decade, many suitable dynamic covalent chemistries were developed to create vitrimer materials, and are now applicable to a wide range of polymer matrices. The material properties of vitrimers, however, do not solely rely on the chemical structure of the polymer matrix, but also on the chemical reactivity of the dynamic bonds. Thus, chemical reactivity considerations become an integral part of material design, which has to take into account for example catalytic and cross-reactivity effects. This mini-review will aim to provide an overview of recent efforts aimed at understanding and controlling dynamic cross-linking reactions within vitrimers, and how directing this chemical reactivity can be used as a handle to steer material properties. Hence, it is shown how a focus on a fundamental chemical understanding can pave the way towards new sustainable materials and applications.

Poly(ethylene glycol) based nanotubes for tuneable drug delivery to glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumour, which is associated with a poor two-year survival rate and a high rate of fatal recurrence near the original tumour. Focal/local drug delivery devices hold promise for improving therapeutic outcomes for GBM by increasing drug concentrations locally at the tumour site, or by facilitating the use of potent anti-cancer drugs that are poorly permeable across the blood brain barrier (BBB). For inoperable tumours, stereotactic delivery to the tumour necessitates the development of nanoscale/microscale injectable drug delivery devices. Herein we assess the ability of a novel class of polymer nanotube (based on poly(ethylene glycol) (PEG)) to load doxorubicin (a mainstay breast cancer therapeutic with poor BBB permeability) and release it slowly. The drug loading properties of the PEG nanotubes could be tuned by varying the degree of carboxylic acid functionalisation and hence the capacity of the nanotubes to electrostatically bind and load doxorubicin. 70% of the drug was released over the first seven days followed by sustained drug release for the remaining two weeks tested. Unloaded PEG nanotubes showed no toxicity to any of the cell types analysed, whereas doxorubicin loaded nanotubes decreased GBM cell viability (C6, U-87 and U-251) in a dose dependent manner in 2D in vitro culture. Finally, doxorubicin loaded PEG nanotubes significantly reduced the viability of in vitro 3D GBM models whilst unloaded nanotubes showed no cytotoxicity. Taken together, these findings show that polymer nanotubes could be used to deliver alternative anti-cancer drugs for local therapeutic strategies against brain cancers.

Focal drug administration via heparin-containing cryogel microcarriers reduces cancer growth and metastasis.

Developing drug delivery systems that release anticancer drugs in a controlled and sustained manner remains challenging. We hypothesized that highly sulfated heparin-based microcarriers would allow electrostatic drug binding and controlled release. In silico modelling showed that the anticancer drug doxorubicin has affinity for the heparin component of the microcarriers. Experimental results showed that the strong electrostatic interaction was reversible, allowing both doxorubicin loading and a subsequent slow release over 42 days without an initial burst release. The drug-loaded microcarriers were able to reduce cancer cell viability in vitro in both hormone-dependent and highly aggressive triple-negative human breast cancer cells. Focal drug treatment, of an in vivo orthotopic triple-negative breast cancer model significantly decreased tumor burden and reduced cancer metastasis, whereas systemic administration of an equivalent drug dose was ineffective. This study proves that heparin-based microcarriers can be used as drug delivery platforms, for focal delivery and sustained long-term drug release.