Incorporating self-healing capability in temperature-sensitive hydrogels by non-covalent chitosan crosslinkers

Through the use of non-covalent chitosan (CS) crosslinkers, reversible yet strong non-covalent interactions are introduced into the poly-N-isopropylacrylamide (PNIPAM) temperature-sensitive hydrogel, which renders desirable mechanical properties, biocompatibility, and most importantly high-level self-healing capability, in combination of facile temperature response near body temperature for drug loading/release. Best overall performance is then reached by optimizing the formulation of CS, N-isopropylacrylamide (NIPAM), acrylic acid (PAA), and acrylamide (AM) in the CS-g-P(NIPAM-AM-AA) graft copolymer system. By virtue of quantum chemical calculations, the nature of a variety of non-covalent interactions within the hydrogel framework is uncovered, those of which between CS and PAM units is found to be superiorly strong, being predominately responsible for the excellent self-healing capability. Synthesis of the hydrogel system simply requires a single-step one-pot procedure, where low cost of all components and the production process is guaranteed. After a series of synthetic optimizations, we notice that hydrogel with NIPAM/AM = 7/1 have the lower critical solution temperature (LCST, 37 °C) corresponding to human body temperature, elongation at break of more than 1500%, strain recovery ratio and stress recovery ratio of 92.89% and 96.15%, remarkable biocompatibility and can provide a good and stable drug loading and release platform. In a nutshell, this study provides a low-cost yet highly viable approach for self-healable thermosensitive hydrogels with biocompatibility, which is appropriate for commercial uses.