Thermo/Shear-Responsive Injectable Hydrogels from an Alginate/PNIPAM-Based Graft Copolymer: Effect of Divalent Cations Ca2+

Abstract

This work is focused on the design and development of biocompatible self-assembling hydrogels, which behave as soft gels at room temperature and strong gels at the physiological temperature, suitable for potential bio-applications. A graft copolymer of sodium-alginate, bearing eight side chains of poly(N-isopropylacrylamide), enriched with the hydrophobic comonomer N-tertiary-butyl-acrylamide (NtBAM), (NaALG-g-P(NIPAM-co-NtBAM)) were used as gelator. In total, 5 wt% aqueous polymer solutions in the presence of Ca2+ cations were prepared and evaluated as thermo-responsive hydrogels. Rheological experiments revealed a twostep reversible gelation either upon heating or cooling. The divalent cations operated as a cross-linking agent through ionic interactions, inducing the formation of a network at low temperatures. Upon heating, an additional crosslinking develops through thermo-induced hydrophobic association of the thermo-responsive P(NIPAM-co-NtBAM) side chains above a critical temperature. The combination of thermo- and shear-responsiveness provides shelf-assembling systems as potential candidates for injectable strategies. For instance, the system under investigation could be used for cell transplantation, which requires a weak gel to protect the cells during injection and a gel strengthening after the injection at a physiological temperature to immobilize the created scaffold in the targeting position of the host tissue.

In situ evaluation of alginate‐Ca2+ gelation kinetics

“…10 Thus, the assessment of the realtime dynamic behavior of these complex biomaterials is crucial to address which parameters control the reaction process. 11 Advanced rheometric methods record the gelation to control and understand the dynamic response of materials. 12 Customized experimental efforts have been recently developed by modifying the transducer in the head of the rheometer to minimize the time of the rheological characterization, 13 or merging rheology with Fourier transform infrared spectroscopy to in situ monitor the chemical and mechanical behavior of gelation.…”

“…An initial fast response in the mechanical properties because of the formation of the first gelling structures is followed by a slow evolution in longer times, where propagation of multimers occurs 10 . Thus, the assessment of the real‐time dynamic behavior of these complex biomaterials is crucial to address which parameters control the reaction process 11 …”