In nature, bone adapts to mechanical forces it experiences, strengthening itself to match the conditions placed upon it. Here we report a composite material that adapts to the mechanical environment ...it experiences-varying its modulus as a function of force, time and the frequency of mechanical agitation. Adaptation in the material is managed by mechanically responsive ZnO, which controls a crosslinking reaction between a thiol and an alkene within a polymer composite gel, resulting in a mechanically driven ×66 increase in modulus. As the amount of chemical energy is a function of the mechanical energy input, the material senses and adapts its modulus along the distribution of stress, resembling the bone remodelling behaviour that materials can adapt accordingly to the loading location. Such material design might find use in a wide range of applications, from adhesives to materials that interface with biological systems.
Mechanical initiation of polymerization offers the chance to generate polymers in new environments using an energy source with unique capabilities. Recently, a renewed interest in mechanically ...controlled polymerization has yielded many techniques for controlled radical polymerization by ultrasound. However, other types of polymerizations induced by mechanical activation are rare, especially for generating high‐molecular‐weight polymers. Herein is an example of using piezoelectric ZnO nanoparticles to generate free‐radical species that initiate chain‐growth polymerization and polymer crosslinking. The fast generation of high amounts of reactive radicals enable the formation of polymer/gel by ultrasound activation. This chemistry can be used to harness mechanical energy for constructive purposes in polymeric materials and for controlled polymerizations for bulk‐scale reactions.
Sound polymerization: Reported is an example of using piezoelectric ZnO nanoparticles to generate free‐radical species that initiate chain‐growth polymerization and polymer crosslinking. The fast generation of high amounts of reactive radicals enabled the formation of a high‐molecular‐weight polymer/gel by ultrasound activation. TDA‐1=tris2‐(2‐methoxyethoxy)ethylamine.
In polymer chemistry, mechanical energy degrades polymeric chains. In contrast, in nature, mechanical energy is often used to create new polymers. This mechanically stimulated growth is a key ...component of the robustness of biological materials. A synthetic system in which mechanical force initiates polymerization will provide similar robustness in polymeric materials. Here we show a polymerization of acrylate monomers initiated and controlled by mechanical energy provided by ultrasonic agitation. The activator for an atom-transfer radical polymerization is generated using piezochemical reduction of a Cu(II) precursor complex, which thus converts a mechanical activation of piezoelectric particles to the synthesis of a new material. This polymerization reaction has some characteristics of controlled radical polymerization, such as narrow molecular-weight distribution and linear dependence of the polymeric chain length on the time of mechanical activation. This new method of controlled radical polymerization complements the existing methods to synthesize commercially useful well-defined polymers.
Mechano‐activated chemistry is a powerful tool for remodeling of synthetic polymeric materials, however, few reactions are currently available. Here we show that using piezochemical reduction of a ...CuII‐based pre‐catalyst, a step‐growth polymerization occurs via the copper catalyzed azide–alkyne cycloaddition (CuAAC) reaction to form a linear polytriazole. Furthermore, we show that a linear polymer can be crosslinked mechanochemically using the same chemistry to form a solid organogel. We envision that this chemistry can be used to harness mechanical energy for constructive purposes in polymeric materials.
Mechano‐Click polymerization: Mechanochemical polymerization using piezochemically driven copper catalyzed azide–alkyne “Click” reaction has been shown here. Ultrasonic activation of piezoelectric nanoparticles was used to generate a CuI catalyst to promote click polymerization and polymer crosslinking. Sonochemical polymerization will provide us with the tools to design polymeric materials that grow or become stronger with mechanical activation.
Frontal polymerization provides a rapid, economic, and environmentally friendly methodology to manufacture thermoset polymers and composites. Despite its efficiency and reduced environmental impact, ...the manufacturing method is underutilized due to the limited fundamental understanding of its dynamic control. This work reports the control and patterning of the front propagation in a dicyclopentadiene resin by immersion of phase‐changing polycaprolactone particles. Predictive and designed patterning is enabled by multiphysical numerical analyses, which reveal that the interplay between endothermic phase transition, exothermic chemical reaction, and heat exchange govern the temperature, velocity, and propagation path of the front via two different interaction regimes. To pattern the front, one can vary the size and spacing between the particles and increase the number of propagating fronts, resulting in tunable physical patterns formed due to front separation and merging near the particles. Both single‐ and double‐frontal polymerization experiments in an open mold are performed. The results confirm the front–particle interaction mechanisms and the shapes of the patterns explored numerically. The present study offers a fundamental understanding of frontal polymerization in the presence of heat‐absorbing second‐phase materials and proposes a potential one‐step manufacturing method for precisely patterned polymeric and composite materials without masks, molds, or printers.
Herein, it is demonstrated that immersing phase‐changing particles with heat absorption capabilities into the resin is a rational route to control the front trajectory, velocity, and temperature in frontal polymerization. The presence of the phase‐changing particles can lead to significant and designable physical patterns with different microstructures in the manufactured part by tuning the front separation and merging near the particles.
A method for fabricating microvascular networks in fiber‐reinforced composites is presented. The method relies on sacrificial fibers woven into fiber preforms that, when removed by depolymerization ...and volatilization, create 3D microvascular networks inside the composite material. By circulation of functional liquids in the resulting channels, a diverse set of new functionality is demonstrated. Simplicity, robustness, scalability, and reliance on readily available components make this method compatible with composite manufacturing methods.
Toll-like receptors (TLRs) are vital elements of the mammalian immune system that function by recognizing pathogen-associated molecular patterns (PAMPs), bridging innate and adaptive immunity. They ...have become a prominent therapeutic target for the treatment of infectious diseases, cancer, and allergies, with many TLR agonists currently in clinical trials or approved as immunostimulants. Numerous studies have shown that conjugation of TLR agonists to other molecules can beneficially influence their potency, toxicity, pharmacokinetics, or function. The functional properties of TLR agonist conjugates, however, are highly dependent on the ligation strategy employed. Here, we review the chemical structural requirements for effective functional TLR agonist conjugation. In addition, we provide similar analysis for those that have yet to be conjugated. Moreover, we discuss applications of covalent TLR agonist conjugation and their implications for clinical use.
Efforts to synthesize degradable polymers from renewable resources are deterred by technical and economic challenges; especially, the conversion of natural building blocks into polymerizable monomers ...is inefficient, requiring multistep synthesis and chromatographic purification. Herein we report a chemoenzymatic process to address these challenges. An enzymatic reaction system was designed that allows for regioselective functional group transformation, efficiently converting glucose into a polymerizable monomer in quantitative yield, thus removing the need for chromatographic purification. With this key success, we further designed a continuous, three‐step process, which enabled the synthesis of a sugar polymer, sugar poly(orthoester), directly from glucose in high yield (73 % from glucose). This work may provide a proof‐of‐concept in developing technically and economically viable approaches to address the many issues associated with current petroleum‐based polymers.
An enzymatic reaction system was designed that allows for regioselective functional group transformation, efficiently converting glucose into a polymerizable monomer without the need for chromatographic purification. A continuous, three‐step process was designed that enables the synthesis of a sugar polymer, sugar poly(orthoester), from glucose in high yield (73 % from glucose).
Neoantigen cancer vaccines that target tumor specific mutations are emerging as a promising modality for cancer immunotherapy. To date, various approaches have been adopted to enhance efficacy of ...these therapies, but the low immunogenicity of neoantigens has hindered clinical application. To address this challenge, we developed a polymeric nanovaccine platform that activates the NLRP3 inflammasome, a key immunological signaling pathway in pathogen recognition and clearance. The nanovaccine is comprised of a poly (orthoester) scaffold engrafted with a small-molecule TLR7/8 agonist and an endosomal escape peptide that facilitates lysosomal rupture and NLRP3 inflammasome activation. Upon solvent transfer, the polymer self-assembles with neoantigens to form ∼50 nm nanoparticles that facilitate co-delivery to antigen-presenting cells. This polymeric activator of the inflammasome (PAI) was found to induce potent antigen-specific CD8+ T cell responses characterized by IFN-γ and GranzymeB secretion. Moreover, in combination with immune checkpoint blockade therapy, the nanovaccine stimulated robust anti-tumor immune responses against established tumors in EG.7-OVA, B16·F10, and CT-26 models. Results from our studies indicate that NLRP3 inflammasome activating nanovaccines demonstrate promise for development as a robust platform to enhance immunogenicity of neoantigen therapies.
Activating innate immunity in a controlled manner is necessary for the development of next-generation therapeutics. Adjuvants, or molecules that modulate the immune response, are critical components ...of vaccines and immunotherapies. While small molecules and biologics dominate the adjuvant market, emerging evidence supports the use of immunostimulatory polymers in therapeutics. Such polymers can stabilize and deliver cargo while stimulating the immune system by functioning as pattern recognition receptor (PRR) agonists. At the same time, in designing polymers that engage the immune system, it is important to consider any unintended initiation of an immune response that results in adverse immune-related events. Here, we highlight biologically derived and synthetic polymer scaffolds, as well as polymer–adjuvant systems and stimuli-responsive polymers loaded with adjuvants, that can invoke an immune response. We present synthetic considerations for the design of such immunostimulatory polymers, outline methods to target their delivery, and discuss their application in therapeutics. Finally, we conclude with our opinions on the design of next-generation immunostimulatory polymers, new applications of immunostimulatory polymers, and the development of improved preclinical immunocompatibility tests for new polymers.
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