Shape morphing of hydrogels by harnessing enzyme enabled mechanoresponse.

Hydrogels have been designed to react to many different stimuli which find broad applications in tissue engineering and soft robotics. However, polymer networks bearing mechano-responsiveness, especially those displaying on-demand self-stiffening and self-softening behavior, are rarely reported. Here, we design a mechano-controlled biocatalytic system at the molecular level that is incorporated into hydrogels to regulate their mechanical properties at the material scale. The biocatalytic system consists of the protease thrombin and its inhibitor, hirudin, which are genetically engineered and covalently coupled to the hydrogel networks. The catalytic activity of thrombin is reversibly switched on by stretching of the hydrogels, which disrupts the noncovalent inhibitory interaction between both entities. Under cyclic tensile-loading, hydrogels exhibit self-stiffening or self-softening properties when substrates are present that can self-assemble to form new networks after being activated by thrombin or when cleavable peptide crosslinkers are constitutional components of the original network, respectively. Additionally, we demonstrate the programming of bilayer hydrogels to exhibit tailored shape-morphing behavior under mechanical stimulation. Our developed system provides proof of concept for mechanically controlled reversible biocatalytic processes, showcasing their potential for regulating hydrogels and proposing a biomacromolecular strategy for mechano-regulated soft functional materials.

Tuning the Elasticity of Nanogels Improves Their Circulation Time by Evading Immune Cells.

Peptide receptor radionuclide therapy is used to treat solid tumors by locally delivering radiation. However, due to nephro- and hepato-toxicity, it is limited by its dosage. To amplify radiation damage to tumor cells, radiolabeled nanogels can be used. We show that by tuning the mechanical properties of nanogels significant enhancement in circulation half-life of the gel could be achieved. We demonstrate why and how small changes in the mechanical properties of the nanogels influence its cellular fate. Nanogels with a storage modulus of 37 kPa were minimally phagocytosed by monocytes and macrophages compared to nanogels with 93 kPa modulus. Using PET/CT a significant difference in the blood circulation time of the nanogels was shown. Computer simulations affirmed the results and predicted the mechanism of cellular uptake of the nanogels. Altogether, this work emphasizes the important role of elasticity even for particles that are inherently soft such as nano- or microgels.

Cellular responses to beating hydrogels to investigate mechanotransduction.

Cells feel the forces exerted on them by the surrounding extracellular matrix (ECM) environment and respond to them. While many cell fate processes are dictated by these forces, which are highly synchronized in space and time, abnormal force transduction is implicated in the progression of many diseases (muscular dystrophy, cancer). However, material platforms that enable transient, cyclic forces in vitro to recreate an in vivo-like scenario remain a challenge. Here, we report a hydrogel system that rapidly beats (actuates) with spatio-temporal control using a near infra-red light trigger. Small, user-defined mechanical forces (~nN) are exerted on cells growing on the hydrogel surface at frequencies up to 10 Hz, revealing insights into the effect of actuation on cell migration and the kinetics of reversible nuclear translocation of the mechanosensor protein myocardin related transcription factor A, depending on the actuation amplitude, duration and frequency.

Micro- and nanopatterned star poly(ethylene glycol) (PEG) materials prepared by UV-based imprint lithography.

A UV-based imprint lithography method is used for the direct surface structuring of hydrogel-based biomaterials, which are prepared from a family of tailor-made star poly(ethylene glycol) formulations. Bulk star poly(ethylene glycol) (PEG) hydrogels are fabricated by cross-linking acrylate-functionalized star PEG macromolecules. Cross-linking is achieved by radical reactions initiated by UV irradiation. This UV-curable star PEG formulation allows templating of mold structures to yield a stable, stand-alone, elastomeric replica of the mold. In particular, when a secondary, soft mold is used that consists of a perfluorinated elastomer with inherent excellent release properties, nanometer-sized features (down to 100 nm) can be imprinted without specialized equipment. The applied UV-based imprint lithography is a fast and simple technique to employ for the direct topographic structuring of bulk PEG-based biomaterials. The UV-based imprinting into the star PEG prepolymer by means of a perfluorinated, soft mold can be carried out on the bench top, while nanoscale resolution is demonstrated.

Melt electrospinning of poly-(ethylene glycol-block-epsilon-caprolactone).

Various block copolymers of poly(ethylene glycol) and poly(epsilon-caprolactone) (PEG-b-PCL) with molecular weights between 7000 and 26,900 g/mol were synthesized, and melt electrospun at temperatures between 60 degrees C and 90 degrees C. Two types of fibers were collected, including excellent quality fibers - highly coiled and continuous, with a constant diameter and relatively defect free. Such fibers, termed "solid fibers", were sufficiently cooled during their path between the spinneret and the collector that the symmetric fiber shape is maintained after landing on the collector. The second type of melt electrospun fiber were poor quality, large diameter fibers, flattened on the collector - termed "molten fibers". The solid and molten fibers were morphologically distinct from each other as determined from scanning electron microscopy (SEM). Using an SEM imaging method to assess the regional variations of collected electrospun material, we found the spinneret pump rate largely influenced the fiber quality. The polymer flow rate to the spinneret and the molecular weight of PEG-b-PCL had the greatest effect on the electrospun fibers collected, with an optimum rate of 0.05-0.1 mL/h for the highest molecular weight copolymers. The lowest molecular weight PEG-b-PCL tended to electrospray, while the material collected from higher molecular weight copolymers were conducive to fiber formation. The highest quality fibers were PEG-b-PCL block copolymers (22,000 and 26,900 g/mol) melt electrospun at temperatures of 85 degrees C and 90 degrees C, corresponding to shear viscosities of the polymer of between 28.1 and 39.4 Pa.S.