Hydrogen-Bonding Reinforced Injectable Hydrogels: Application As a Thermo-Triggered Drug Controlled-Release System

Most injectable hydrogels are prone to irreversible deformation or damage under sustained shear forces and exhibit low mechanical properties, which limit their practical applications in biological engineering. In this work, the first hydrogen-bonding reinforced injectable thermoresponsive hydrogel system has been fabricated through an in situ hydrazide–aldehyde cross-linking reaction between hydrazide-functionalized poly(N-isopropylacrylamide) (PNIPAM) and dialdehyde dextrin. The mechanical strength and stability of the hydrogel were reinforced by the introduction of intermolecular hydrogen-bonding from poly(N-acryloyl glycinamide) (PNAGA), which possesses great biocompatibility and similarity to PNIPAM. The internal morphology, dynamic moduli, de-cross-linking properties, and temperature responsiveness of the hydrogels were systematically investigated. Upon hydrogen-bonding reinforcement, the hydrogel elasticity, reflected by the maximum storage modulus, dramatically increased from 90.2 to 517.0 kPa, which is about a 570% increase compared with unreinforced hydrogels. In addition, the mechanical properties of the hydrogel were reinforced as the de-cross-linking could be inhibited by PNAGA-based hydrogen-bonding. The temperature release behavior of the hydrogel was assessed with a model drug (propranolol hydrochloride, PHCl) and could be precisely controlled by adjusting the environmental temperature between 25 and 37 °C. Therefore, PNAGA reinforced thermoresponsive hydrogels are promising functional biological materials for use in tissue-repair engineering and controlled-release drug delivery.