Preparation And Research Of Stimuli-Responsive Hydrogels Based On Chitosan Quaternary Ammonium Salts

Stimuli-responsive hydrogels are widely used in various fields,including biomedical,energy,and agricultural applications.Common substrates for natural-based stimuli-responsive hydrogels include DNA,proteins,peptides,and polysaccharides.Chitosan,a natural alkaline polysaccharide,is widely used in biopharmaceutical and food packaging industries,but its poor solubility limits its use.Chitosan quaternary ammonium salt,a water-soluble derivative of chitosan,has good antibacterial and histocompatibility properties,but chitosan quaternary ammonium salt still lacks sufficient stimulus responsiveness to perform around the influence of external stimuli.Light is one of the most common sources of stimulation.Photothermal materials are a class of photosensitive materials,which is capable of converting light energy into heat under the irradiation of specific wavelengths of light.Tannic acid-iron complexes are of natural origin,easy to synthesize,and have good photothermal effects,allowing rapid warming under near-infrared light.Temperature stimulation is also easy to control,and poly（N-isopropyl acrylamide）（PNIPAM）hydrogels,temperature-sensitive smart materials with phase transition temperatures close to body temperature,have been intensively studied in the direction of drug release,tissue engineering,and biosensing,but they lack sufficient bioactivity and therefore also require functionalized modification.In this paper,a rational mix and design were carried out to first develop an efficient photothermal antibacterial hydrogel based on chitosan quaternary ammonium salt,tannic acid,and iron ions.This was followed by the development of a PNIPAM/chitosan quaternary ammonium salt-based hydrogel loaded with bioactive factors,which simultaneously provided the anti-inflammatory,pro-repair,and remodeling functions required in the repair of bone defects.Details of the research are as follows.（1）Firstly,a novel photothermal antibacterial hydrogel was prepared using chitosan quaternary ammonium salt as substrate and through its physical interaction with tannic acid-iron complexes,and its structure was characterized using IR spectroscopy,UV spectroscopy,and ¹H NMR.SEM,swelling,and water evaporation rate results showed that the degree of cross-linking of the hydrogel increased with the increase of Fe³⁺concentration and the introduction of Fe³⁺led to the photothermal conversion tests also showed that the hydrogels had good photothermal properties with a maximum photothermal conversion efficiency of over 37%.The inherent antibacterial properties of chitosan quaternary ammonium salts and the synergistic photothermal effect exhibited ideal antibacterial ability,producing significant damage to the bacterial cell surface,meanwhile the hydrogel exhibited low cytotoxicity,thus possessing the potential to become a novel antibacterial material for medical use.（2）PNIPAM was compounded with chitosan quaternary ammonium salt and tannic acid-iron complex to prepare a dual stimuli-responsive antimicrobial hydrogel with both temperature-sensitive and light-sensitive properties.Later,a novel temperature-sensitive photothermal hydrogel with both anti-inflammatory and bone differentiation-promoting repair capabilities was developed by adding the bone growth factor BMP-2 to the composite hydrogel for application in the treatment of bone defects.This PNIPAM-based hydrogel exhibits significant volume contraction and morphological changes upon temperature increase.SEM and swelling rates of the prepared hydrogel after temperature change showed that the three-dimensional network of the hydrogel contracted significantly,facilitating the release of loaded growth factors.At the same time,the pigskin adhesion test and the rheological test showed that the hydrogels possess excellent adhesion and self-healing ability,and have stable photothermal properties with antibacterial and antioxidant abilities.The results of osteoblast differentiation showed that the hydrogel can effectively stimulate the proliferation and differentiation of osteoblasts,and the"hot spring effect"provided by the photothermal effect resulted in a deepening of ALP staining and a significant up-regulation of osteogenic growth factors such as COL1 and RUNX2,which significantly promoted the osteogenic differentiation,demonstrating the usefulness of the hydrogel as a smart material in vitro.The experiments have shown the potential of this hydrogel as a smart material in the field of bone repair.