Thiol Cross-linking Research Articles

Synthesis and Solvent Free DLP 3D Printing of Degradable Poly(Allyl Glycidyl Ether Succinate)

AbstractDigital light processing (DLP) printing forms solid constructs from fluidic resins by photochemically crosslinking polymeric resins with reactive functional groups. DLP is used widely due to its efficient, high‐resolution printing, but its use and translational potential has been limited in some applications as state‐of‐the‐art resins experience unpredictable and anisotropic part shrinkage due to the use of solvent needed to reduce resin viscosity and layer dependent crosslinking. Herein, poly(allyl glycidyl ether succinate) (PAGES), a low viscosity, degradable polyester, was synthesized by ring opening copolymerization and used in combination with degradable thiol crosslinkers to afford a solvent free resin that can be utilized in DLP printing. Varying resin formulations of PAGES polymer are shown to decrease part shrinkage from 14 % to 0.3 %. Photochemically printed parts fabricated from PAGES possess tensile moduli between 0.43 and 6.18 MPa and degradation profiles are shown to vary between 12 and 40 days under accelerated conditions based on degree of polymerization and crosslink ratio.

Digital Light Processing (DLP) 3D Printing of Caprolactone Copolymers with Tailored Properties through Crystallinity.

Digital light processing (DLP) 3D printing has shown great advantages such as high resolution in the fabrication of 3D objects toward a range of applications. Despite the rapid development of photocurable materials for DLP printing, tailoring properties to meet the specific demands for various applications remains challenging. Herein, we introduce copolymers of caprolactone and allyl caprolactone offering built-in functionality for thiol-ene photochemistry, thereby omitting the need for postfunctionalization. A crystalline block copolymer and an amorphous statistical copolymer were synthesized with the same comonomer composition and molecular weight. Thio-ene photocuring with a tetrafunctional thiol cross-linker was studied at different thiol to double-bond ratios for the copolymers and their blends. All formulations undergo rapid photocuring within several seconds of irradiation with slightly higher gel fractions observed for the statistical copolymer over the block copolymer under the same conditions, suggesting a somewhat higher cross-link density. Thermal properties of the networks were dependent on the presence of the semicrystalline block copolymer, where higher melting enthalpies were reached at higher block copolymer content. Similarly, crystallinity was found to be the main contributor to the mechanical properties. For a comparable composition, the modulus of a block copolymer network was found to be 31 times higher than that of the statistical copolymer network (27.7 vs 0.89 MPa). Intermediate moduli could be obtained by blending the two copolymers. DLP-printed scaffolds from these copolymers retained their thermal properties, therefore offering an efficient approach to tailoring mechanical properties, through crystallinity. Moreover, the printed scaffold displayed shape memory properties as the first example of poly(carprolactone) (PCL) copolymers in DLP printing. These materials are readily synthesized, offer fast and high-resolution 3D printing, and are degradable and cell compatible. They offer a straightforward approach to tailoring properties of PCL-based biomaterials and devices.

Synthesis and Solvent Free DLP 3D Printing of Degradable Poly(Allyl Glycidyl Ether Succinate).

Digital light processing (DLP) printing forms solid constructs from fluidic resins by photochemically crosslinking polymeric resins with reactive functional groups. DLP is used widely due to its efficient, high-resolution printing, but its use and translational potential has been limited in some applications as state-of-the-art resins experience unpredictable and anisotropic part shrinkage due to the use of solvent needed to reduce resin viscosity and layer dependent crosslinking. Herein, poly(allyl glycidyl ether succinate) (PAGES), a low viscosity, degradable polyester, was synthesized by ring opening copolymerization and used in combination with degradable thiol crosslinkers to afford a solvent free resin that can be utilized in DLP printing. Varying resin formulations of PAGES polymer are shown to decrease part shrinkage from 14% to 0.3%. Photochemically printed parts fabricated from PAGES possess tensile moduli between 0.43 and 6.18 MPa and degradation profiles are shown to vary between 12 and 40 days under accelerated conditions based on degree of polymerization and crosslink ratio.

Light Switchable Bioorthogonal Reaction Manifold for Modulation of Hydrogel Properties.

Chemical reaction systems that can occur via multiple pathways in a controllable fashion are highly attractive for advanced materials applications and biological research. In this report, we introduce a bioorthogonal reaction manifold based on a chalcone pyrene (CPyr) moiety that can undergo either red-shifted photoreversible [2 + 2] cycloaddition or thiol-Michael addition click reaction. By coupling the CPyr to a water-soluble poly(ethylene glycol) end group, we demonstrate the efficient polymer dimerization and cleavage by blue light (λ = 450 nm) and UV light (λ = 340 nm), respectively. In the absence of light, CPyr rapidly reacts with thiols in aqueous environments, enabling fast and efficient polymer end-group functionalization. The chemical reaction manifold was further employed in polymer cross-linking for the preparation of hydrogels whose stiffness and morphology can be modulated by different photonic fields or the addition of a thiol cross-linker. The photoreversible cycloaddition and thiol-Michael addition click reaction can be used in conjunction for spatial and temporal conjugation of a streptavidin protein. Both cross-linking conditions are nontoxic to various cell lines, highlighting their potential in biomaterials applications.

Reshapable bio-based thiol-ene vitrimers for nanoimprint lithography: Advanced covalent adaptability for tunable surface properties

Taking inspiration from natural surfaces known for their ability to adaptively remodel their shape, we fabricated stimuli-responsive microstructures by using UV-induced nanoimprint lithography. For this, a fully bio-based dynamic thiol-ene photopolymer was synthetized by the radical mediated addition of a trifunctional eugenol-based thiol (SH3E) crosslinker across an allylated linseed oil (ALELO). To catalyze the bond exchange reactions between the hydroxyl and ester groups within the network, a bio-based eugenol phosphate ester was introduced as a transesterification catalyst. Pure eugenol was further added as a reactive diluent to increase the number of hydroxyl groups and thus, accelerate the thermo-activated bond exchange reactions. Once cured by UV exposure, the dynamic photopolymer is thermally stable up to 250 °C and is able to relax 63% of the original stress within 62 min at 160 °C. Subsequently, films with micropillars, having an aspect ratio of 1:2.5 were prepared by using nanoimprint lithography. The macroscopic reflow capability of the dynamic network enabled a reorientation of the imprinted structures during a thermal reshaping step. The imprints were characterized by 2D/3D optical microscopy, μCT imaging and static water contact angle measurements. Based on the orientation of the micropillars, the water contact angle was varied between 118° and 95°, giving rise to a possible application in microfluidic devices.

Bio-Based Thiol-ene Network Thermosets from Isosorbide and Terpenes.

Thermoset networks are chemically cross-linked materials that exhibit high heat resistance and mechanical strength; however, the permanently cross-linked system makes end-of-life degradation difficult. Thermosets that are inherently degradable and made from renewably derived starting materials are an underexplored area in sustainable polymer chemistry. Here, we report the synthesis of novel sugar- and terpene-based monomers as the enes in thiol-ene network formation. The resulting networks showed varied mechanical properties depending on the thiol used during cross-linking, ranging from strain-at-breaks of 12 to 200%. Networks with carveol or an isosorbide-based thiol incorporated showed plastic deformation under tensile stress testing, while geraniol-containing networks demonstrated linear stress-strain behavior. The storage modulus at the rubbery plateau was highly dependent on the thiol cross-linker, showing an order of magnitude difference between commercial PETMP, DTT, and synthesized Iso2MC. Thermal degradation temperatures were low for the networks, primarily below 200 °C, and the Tg values ranged from -17 to 31 °C. Networks were rapidly degraded under basic conditions, showing complete degradation after 2 days for nearly all synthesized thermosets. This library demonstrates the range of thermal and mechanical properties that can be targeted using monomers from sugars and terpenes and expands the field of renewably derived and degradable thermoset network materials.

Mucus-coated, magnetically-propelled fecal surrogate to mimic fecal shear forces on colonic epithelium

The relationship between the mechanical forces associated with bowel movement and colonic mucosal physiology is understudied. This is partly due to the limited availability of physiologically relevant fecal models that can exert these mechanical stimuli in in vitro colon models in a simple-to-implement manner. In this report, we created a mucus-coated fecal surrogate that was magnetically propelled to produce a controllable sweeping mechanical stimulation on primary intestinal epithelial cell monolayers. The mucus layer was derived from purified porcine stomach mucins, which were first modified with reactive vinyl sulfone (VS) groups followed by reaction with a thiol crosslinker (PEG-4SH) via a Michael addition click reaction. Formation of mucus hydrogel network was achieved at the optimal mixing ratio at 2.5 % w/v mucin-VS and 0.5 % w/v PEG-4SH. The artificial mucus layer possessed similar properties as the native mucus in terms of its storage modulus (66 Pa) and barrier function (resistance to penetration by 1-μm microbeads). This soft, but mechanically resilient mucus layer was covalently linked to a stiff fecal hydrogel surrogate (based on agarose and magnetic particles, with a storage modulus of 4600 Pa). The covalent bonding between the mucus and agarose ensured its stability in the subsequent fecal sliding movement when tested at travel distances as long as 203 m. The mucus layer served as a lubricant and protected epithelial cells from the moving fecal surrogate over a 1 h time without cell damage. To demonstrate its utility, this mucus-coated fecal surrogate was used to mechanically stimulate a fully differentiated, in vitro primary colon epithelium, and the physiological stimulated response of mucin-2 (MUC2), interleukin-8 (IL-8) and serotonin (5HT) secretion was quantified. Compared with a static control, mechanical stimulation caused a significant increase in MUC2 secretion into luminal compartment (6.4 × ), a small but significant increase in IL-8 secretion (2.5 × and 3.5 × , at both luminal and basal compartments, respectively), and no detectable alteration in 5HT secretion. This mucus-coated fecal surrogate is expected to be useful in in vitro colon organ-on-chips and microphysiological systems to facilitate the investigation of feces-induced mechanical stimulation on intestinal physiology and pathology.

Water-in-oil emulsion templated polyurethanes with uniform porosity

Porous PU foams have been receiving great attention because of their low density, lightweight, and high surface area. However, preparing PU foams with controlled porosity, pore size, and pore morphology is often difficult with commonly used methods like gas blowing. Here, highly controllable porous PU with small, uniform pore morphology and tunable material properties have been synthesized using water-in-oil polymerized high internal phase emulsion (PolyHIPE) templating and photoinitiated thiol-ene reactions between vinyl-functionalized polyurethane prepolymers and thiol-functionalized crosslinkers. The PolyHIPEs exhibited highly interconnected open-cell structures with pore sizes ranging from 5 to 10 μm. The storage moduli and elastic moduli of PU polyHIPEs derived from flexible HDI-PUs were low compared to stiff IPDI-PU based polyHIPEs. Furthermore, the storage moduli of relatively soft HDI-PU polyHIPEs were affected by the stoichiometric ratio of thiol crosslinker and vinyl-PU whereas no considerable effect on the stiffer IPDI-PU based polyHIPEs. In summary, this work presents an approach to synthesize porous polyurethane polyHIPEs with potential applications in aerospace, automotive, and biomedical industries.

Suspension electrospinning of SBR latex combined with photo-induced crosslinking: control of nanofiber composition, morphology, and properties

Suspension electrospinning of a styrene-butadiene rubber (SBR) latex coupled with photo-induced crosslinking in ambient conditions is proposed as a rapid method to prepare ultrafine shape-stable rubber fibrous membranes. Polyethylene oxide (PEO) is used as template polymer and can eventually be removed from the nanostructured membrane by a simple water treatment. A multifunctional thiol crosslinker and an appropriate photo-initiating system are added to the latex to allow the fast and efficient photo-induced crosslinking of the nanofibers, based on thiol addition to the SBR double bonds, as demonstrated by real-time Infrared spectroscopy analyses. It is proved that by varying the PEO template polymer and the thiol crosslinker content, a fine control of the chemical composition, morphology, water solubility, and thermal properties of the nanofibrous membranes is ensured. Moreover, comparable mechanical properties to those of fibrous membranes produced by conventional electrospinning of organic solvent-based solutions are obtained, clearly showing the attractiveness of the present method, especially in terms of process sustainability.Graphical abstract

Easily recycled thiol-ene elastomers with controlled creep

Starting from in-house synthesized allylic monomers containing dynamic disulfide (SS) bonds, a set of vitrimeric thiol-ene elastomers were prepared and characterized with respect to their viscoelastic and tensile properties. A mixture of a disulfide-containing diallyl monomer and disulfide-free diallyl, namely diallyl phthalate, was combined stoichiometrically with a thiol crosslinker, trimethylolpropane tris (3-mercaptopropionate), to obtain soft thiol-ene thermosets with varying degrees of dynamic bond content. The materials were able to relax strain induced stress completely and rapidly at moderately high temperatures when the disulfide content was above a certain threshold, which was accurately predicted by a statistically-based network (de)crosslinking model. Relaxation of materials with disulfide content below this threshold required the activation of an additional transesterification bond exchange process by increasing the temperature. Recycling of the materials could be achieved by hot-press molding at convenient temperatures. Especially in low-disulfide containing materials, changes were observed in the material structure and properties with increasing number of reprocessing cycles. However, a significant reduction in ambient temperature creep was observed upon reducing the disulfide content. The disulfide content can be easily optimized to yield minimal loss of mechanical property and minimal creep. This work opens up new avenues for the cost-effective development of vitrimeric elastomers with minimal ambient temperature creep.

Gastropod Slime-Based Gel as an Adjustable Synthetic Model for Human Airway Mucus.

Airway mucus works as a protective barrier in the human body, as it entraps pathogens that will be later cleared from the airways by ciliary transport or by coughing, thus featuring the rheological properties of a highly stretchable gel. Nonetheless, the study of these physical barrier as well as transport properties remains limited due to the restricted and invasive access to lungs and bronchi to retrieve mucus and to the poor repeatability inherent to native mucus samples. To overcome these limits, we report on a biobased synthetic mucus prepared from snail slime and multibranched thiol cross-linker, which are able to establish disulfide bonds, in analogy with the disulfide bonding of mucins, and therefore build viscoelastoplastic hydrogels. The gel macroscopic properties are tuned by modifying the cross-linker and slime concentrations and can quantitatively match those of native sputum from donors with cystic fibrosis (CF) or non-cystic fibrosis bronchiectasis (NCFB) both in the small- and large-deformation regimes. Heterogeneous regimes were locally found in the mucus model by passive microrheology, in which both diffusive and non-diffusive motion are present, similar to what is observed in sputa. The biobased synthetic approach proposed in the present study thus allows to produce, with commercially available components, a promising model to native respiratory mucus regarding both mechanical and, to a lesser extent, physicochemical aspects.

Volumetric Printing of Thiol‐Ene Photo‐Cross‐Linkable Poly(ε‐caprolactone): A Tunable Material Platform Serving Biomedical Applications (Adv. Mater. 19/2023)

Volumetric 3D Printing In volumetric 3D printing, the whole 3D object is developed simultaneously (i.e., volume-at-once) by means of light-induced crosslinking of a (rotating) liquid resin, as reported by Sandra Van Vlierberghe and co-workers in article number 2210136. The 3D-structure illustrated in the image is based on the chemical network structure of the reported thiol–ene crosslinked poly(caprolactone) (PCL) network, which can be considered a homogeneous 3D network consisting of telechelic alkene-functionalized PCL and tetra-functional thiol crosslinker junctions.

Resin-supported cyclic telluride as a heterogeneous promoter of disulfide formation under solid–liquid biphasic conditions

A resin-supported cyclic telluride effectively promoted oxidation of thiols in polypeptides as well as small molecules in a solid–liquid biphasic reaction system, providing the corresponding pure disulfide states without a purification process.

A novel photocurable pullulan-based bioink for digital light processing 3D printing.

Digital light processing has significant advantages, such as high repeatability, low failure rate, and no extrusion shear force. To make it possible to print complex structures with high resolution, the consecutive development of photocurable ink materials is indispensable. In this work, photo-functionalized pullulan (Pul-NB) was prepared by introducing norbornene groups into pullulan chains, and an ink material suitable for photocurable printing was prepared by thiol-ene click reaction. The rheology, water absorption, and mechanical properties of the Pul-NB precursor solution and photocurable hydrogel were investigated. The optimal composition of Pul-NB ink for three-dimensional (3D) printing was obtained by adjusting the degree of substitution, Pul-NB concentration, and thiol crosslinking agent. This novel bioink for digital light processing 3D printing showed good printability and high shape fidelity. This ink material provides an excellent alternative for printing biomimetic soft tissue organs, high-throughput tissue models, soft robots, etc.

Polymer Materials Synthesized through Cell-Mediated Polymerization Strategies for Regulation of Biological Functions

ConspectusAs essential components of living organisms, biomacromolecules construct cell scaffolds and regulate cell activities and biological functions through chemical transformations in biological systems. Inspired by the functional evolution in the formation of natural structures, in situ polymerization methods have been developed to create functional synthetic macromolecules inside or on the surface of living cells. Given the diversity of cell species and the complexity of biological pathways, selected strategies can be employed to control the synthesis of functional polymers that utilize the dynamic cellular microenvironment.In this Account, we summarize recent work in the field of designing cell-mediated in situ polymerization methods, with which we demonstrate their application prospects including tumor cell labeling and treatment, microbial photosynthetic efficiency regulation, and hydrogel generation. The purpose of these efforts is to design polymerization reactions in response to endogenous or exogenous stimuli and to describe the underlying response mechanisms. By reasonable design of molecular structures, in situ synthesized polymers in the cell microenvironment implement regulation of biological functions. For example, using specific redox activity combined with light irradiation, bacteria can mediate the generation of functional polymers as the encapsulating matrix or with antibacterial effects. Conjugated polymers synthesized on the microalgae surface expanded the spectral absorption and improved photosynthetic efficiency. Meanwhile, characteristics of the cellular microenvironment could initiate various polymerization reactions inside living cells, including oxidative thiol cross-linking, condensation polymerization, and free radical polymerization. These reactions can be selectively conducted with reactive species generated in tumor cells, and the resulting polymers showed prolonged retention inside cells for modulating cell behaviors. Further development of cell-mediated polymerization strategies would provide an innovative platform for research and applications of multifunctional biomaterials and engineered biohybrid systems.

Vat Photopolymerization 3D-Printing of Dynamic Thiol-Acrylate Photopolymers Using Bio-Derived Building Blocks.

As an energy-efficient additive manufacturing process, vat photopolymerization 3D-printing has become a convenient technology to fabricate functional devices with high resolution and freedom in design. However, due to their permanently crosslinked network structure, photopolymers are not easily reprocessed or repaired. To improve the environmental footprint of 3D-printed objects, herein, we combine the dynamic nature of hydroxyl ester links, undergoing a catalyzed transesterification at elevated temperature, with an acrylate monomer derived from renewable resources. As a sustainable building block, we synthesized an acrylated linseed oil and mixed it with selected thiol crosslinkers. By careful selection of the transesterification catalyst, we obtained dynamic thiol-acrylate resins with a high cure rate and decent storage stability, which enabled the digital light processing (DLP) 3D-printing of objects with a structure size of 550 µm. Owing to their dynamic covalent bonds, the thiol-acrylate networks were able to relax 63% of their initial stress within 22 min at 180 °C and showed enhanced toughness after thermal annealing. We exploited the thermo-activated reflow of the dynamic networks to heal and re-shape the 3D-printed objects. The dynamic thiol-acrylate photopolymers also demonstrated promising healing, shape memory, and re-shaping properties, thus offering great potential for various industrial fields such as soft robotics and electronics.

Thiol-ene eugenol polymer networks with chemical Degradation, thermal degradation and biodegradability

A green and sustainable strategy is developed toward the synthesis of methacrylic monomers and polymer networks using biobased eugenol as a starting material via solvent-free thiol-ene click chemistry. The mechanical properties, thermal stability, cross-linking density, glass transition temperature and transparency of biobased polymer networks can be tuned by changing the types of eugenol-based monomers and thiol crosslinkers. These polymer networks can be chemically degraded into carboxylic acids and other small molecules under basic conditions and could further thermally degrade into CO and CO2. 8 %(0.2 g) of the network was biodegraded in digestive system of Tenebrio molitor. Biodegradation products of these polymer networks mainly include volatile organics, biological wastes, and other biodegraded intermediates. These polymers and their degradation mechanisms could provide a pathway to accessing degradable sustainable polymers and materials containing biomass resources.

Efficient synthesis of S-protected thiolated polysaccharide xylan

Since thiolated polysaccharides are valuable reactive carriers for thiol-ene reaction and thiol-disulfide exchange, we investigated a sophisticated method that avoids the crosslinking of thiols during polymer modification. Hydroxyl groups of xylan were activated by forming the phenylcarbonates and exploit as coupling group. The reactive xylan phenylcarbonates were allowed to react with the aminium chloride group under base addition to form the corresponding carbamate bond. The pKb of the base used was crucial for the successful synthesis. A pyridyl disulfide was applied as terminal functional moiety, which is not only a S-protected- but also an activated thiol for the synthesis of functional polysaccharide disulfides. The deprotected thiol, obtained by reduction of the disulfide, could be converted with a functional thiol. On the one hand, we have developed a valuable method to make disulfide chemistry easily accessible for the modification of neutral polysaccharides. On the other hand, the novel cationic polysaccharide derivative, where the functional group is bound by a reduction-sensitive disulfide bond, is an appealing product suitable for gene delivery applications.

Thermadapt shape memory polymers based on thermally induced dynamic covalent quinone methide–thiol click reaction

A novel thermadapt shape memory polymer networks were prepared based on the conjugate addition reaction of quinone methide (QM) end-group-functionalized polycaprolactone and a thiol cross-linker, which can undergo the dynamic exchange reaction under thermal stimulation conditions. The resultant cross-linked polymers possessed excellent elasticity-based shape memory performance, cycle stability and solid-state plastically characteristics under high temperature conditions. This thermal-induced QM-thiol dynamic covalent click chemistry provided an effective method for realizing the solid-state plasticity of the polymers.

Thiol-Based Three-Dimensional Printing of Fully Degradable Poly(propylene fumarate) Star Polymers.

Poly(propylene fumarate) star polymers photochemically 3D printed with degradable thiol cross-linkers yielded highly tunable biodegradable polymeric materials. Tailoring the alkene:thiol ratio (5:1, 10:1, 20:1 and 30:1) and thus the cross-link density within the PPF star systems yielded a wide variation of both the mechanical and degradation properties of the printed materials. Fundamental trends were established between the polymer network cross-link density, glass transition temperature, and tensile and thermomechanical properties of the materials. The tensile properties of the PPF star-based systems were compared to commercial state-of-the-art non-degradable polymer resins. The thiolene-cross-linked materials are fully degradable and possess properties over a wide range of mechanical properties relevant to regenerative medicine applications.