High Strength Chitosan Hydrogels with Biocompatibility via New Avenue Based on Constructing Nanofibrous Architecture

Abstract

Breaking the limitation of traditional acid dissolving methods for chitosan by creating an alkali/urea hydrogen-bonded chitosan complex, a new solvent (4.5 wt % LiOH/7 wt % KOH/8 wt % urea aqueous solution) was used to successfully dissolve chitosan via the freezing−thawing process, for the first time. Subsequently, high strength hydrogels with unique nanofibrous architecture were constructed from the chitosan alkaline solution. The results from 13 C NMR, laser light scattering, atomic force microscopy, transmission electron microscopy, and scanning electron microscopy confirmed that chitosan easily aggregated in the solution and could self-assemble in parallel to form perfect regenerated nanofibers induced by heating. At elevated temperature and concentration, the regenerated chitosan nanofibers could entangle and cross-link with each other through hydrogen bonds to form hydrogels. The novel chitosan hydrogels exhibited homogeneous architecture and high strength as a result of the strong networks woven with the compact nanofibers. The compression fracture stress of the chitosan hydrogels was nearly 100 times that of the chitosan hydrogels prepared by the traditional acid dissolving method, revealing that the nanofibrous network microstructures contributed greatly to the reinforcement of the hydrogels. Furthermore, the chitosan hydrogels exhibited excellent biocompatibility and safety as well as a smart controlled drug release behavior triggered by acid. Therefore, we opened up a completely new avenue to construct high strength chitosan hydrogels for applications in biomedicine. ■ INTRODUCTIONHydrogels are composed of three-dimensional polymer networks that contain abundant water in the porous structures, and their soft and rubbery consistency and low interfacial tension with water or biological fluids are common to human tissues. 1−3 Recently, the potential of polysaccharide-based hydrogels as biomaterials has been widely recognized due to their excellent biocompatibility, biological activity, safety, and biodegradability. 4−6 Chitosan, the unique alkaline polysaccharide derived from the deacetylation of chitin, is readily soluble in dilute acidic solutions, and chitosan hydrogels can be regenerated by using alkaline coagulating bath. Thanks to their intrinsic biocompatibility, nontoxicity, biodegradability, strong affinity, antimicrobial activity, and low immunogenicity, chitosan hydrogels are considered to have potential applications in a wide variety of fields such as water treatment, food industry, catalysis, agriculture, and biomedicine. 7−12 However, the poor mechanical properties, the "Achilles' heel" of chitosan hydrogels, are serious impediments for their practical applications. 13,14 To date, several methods such as chemical cross-linking, nanofillers reinforcement (e.g., nanoclay, silica nanoparticles, carbon nanotube, and graphene), and blending with other polymers have been used to enhance their mechanical strength. However, these techniques resulted in only a moderate enhancement and sometimes even...

Spherical nanocomposite particles prepared from mixed cellulose–chitosan solutions

“…Commercial grade chitosan from shrimp shells was supplied by Regal Biology Ltd. (China), and the degree of deacetylation was determined to 89 % by potentiometric titration (Duan et al 2015b). The other chemicals; lithium hydroxide (LiOH), potassium hydroxide (KOH), urea, acetic acid, epichlorohydrin, t-BuOH, isooctane and Span Ò 80, were of analytical grade and supplied by Shanghai SHENSHI Chemical Co, Ltd (Shanghai, China).…”

“…A 4 wt% transparent cellulose solution was obtained after removing the air bubbles by centrifuging the sample at 8000 rpm and 0°C for 10 min. Chitosan solutions were prepared in two manners; conventional dissolution in 1 % acetic acid and dissolution in LiOH/KOH/ urea (Duan et al 2015b). The 1 wt% solution of chitosan in acetic acid was prepared by mixing the required amount of chitosan in 1 % acetic acid at room temperature.…”

“…At the given mixing ratio the cellulose-chitosan solution did not show any signs of phase separation. To induce crosslinking between cellulose and chitosan, epichlorohydrin was added to the mixture (Chang et al 2010;Duan et al 2015b). Meanwhile, an oil phase was prepared by mixing isooctane and Span Ò 80 (100:1 v/v) at 1300 rpm for 30 min at room temperature in a threeneck round-bottom flask.…”

“…The results from the particle size analysis confirm the qualitative observations from FE-SEM that the CCMS-CL particles are larger on average than the CCMS ones. When epichlorohydrin was applied in the premixing of cellulose and chitosan solutions, a polymer network induced by crosslinked hydroxyl groups among cellulose and chitosan was established (Duan et al 2015b). Since the crosslinked polymers were not as free or flexible as in the case of CCMS, where only physical interactions were present, larger spheres were preferably formed.…”

“…Cellulose and chitosan were dissolved in LiOH/urea and LiOH/KOH/urea solvents, respectively, via a freezing-thawing process (Duan et al 2015b). Cellulose-chitosan particles (CCP) were obtained by dripping cellulose solution into a solution of chitosan in a dilute acetic acid.…”