Thermoresponsive Injectable Hydrogels Cross-Linked by Native Chemical Ligation

Temperature-induced physical gelation was combined with native chemical ligation (NCL) as a chemical cross-linking mechanism to yield rapid network formation and mechanically strong hydrogels. To this end, a novel monomer <i>N</i>-(2-hydroxypropyl)­methacrylamide-cysteine (HPMA-Cys) was synthesized that copolymerizes with <i>N</i>-isopropylacrylamide (NIPAAm) to yield thermoresponsive polymers decorated with cysteine functionalities. Triblock copolymers consisting of a poly­(ethylene glycol) (PEG) middle block flanked by random blocks of NIPAAm and HPMA-Cys were successfully synthesized and characterized. Additionally, thioester cross-linkers were synthesized based on PEG and hyaluronic acid, respectively. Upon mixing the thermoresponsive polymer with PEG or hyaluronic acid cross-linker, cysteine and thioester functionalities react under physiological conditions to generate a native peptide bond. An immediate physical network was formed after elevation of the temperature to 37 °C due to the self-assembly of the pNIPAAm chains. This network was stabilized in time by covalent cross-linking due to NCL reaction between thioester and cysteine functionalities, resulting in hydrogels with up to 10 times higher storage moduli than without chemical cross-links. Finally, a collagen mimicking peptide sequence was successfully ligated to this hydrogel using the same reaction mechanism, showing the potential of this hydrogel for tissue engineering applications

Swelling Enhanced Remanent Magnetization of Hydrogels Cross-Linked with Magnetic Nanoparticles

Hydrogels that are pH-sensitive and partially cross-linked by cobalt ferrite nanoparticles exhibit remarkable remanent magnetization behavior. The magnetic fields measured outside our thin disks of ferrogel are weak, but in the steady state, the field dependence on the magnetic content of the gels and the measurement geometry is as expected from theory. In contrast, the time-dependent behavior is surprisingly complicated. During swelling, the remanent field first rapidly increases and then slowly decreases. We ascribe the swelling-induced field enhancement to a change in the average orientation of magnetic dipolar structures, while the subsequent field drop is due to the decreasing concentration of nanoparticles. During shrinking, the field exhibits a much weaker time dependence that does not mirror the values found during swelling. These observations provide original new evidence for the markedly different spatial profiles of the pH during swelling and shrinking of hydrogels