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

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 ¹³C 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

Effects of Chitin Whiskers on Physical Properties and Osteoblast Culture of Alginate Based Nanocomposite Hydrogels

Novel nanocomposite hydrogels composed of polyelectrolytes alginate and chitin whiskers with biocompatibility were successfully fabricated based on the pH-induced charge shifting behavior of chitin whiskers. The chitin whiskers with mean length and width of 300 and 20 nm were uniformly dispersed in negatively charged sodium alginate aqueous solution, leading to the formation of the homogeneous nanocomposite hydrogels. The experimental results indicated that their mechanical properties were significantly improved compared to alginate hydrogel and the swelling trends were inhibited as a result of the strong electrostatic interactions between the chitin whiskers and alginate. The nanocomposite hydrogels exhibited certain crystallinity and hierarchical structure with nanoscale chitin whiskers, similar to the structure of the native extracellular matrix. Moreover, the nanocomposite hydrogels were successfully applied as bone scaffolds for MC3T3-E1 osteoblast cells, showing their excellent biocompatibility and low cytotoxicity. The results of fluorescent micrographs and scanning electronic microscope (SEM) images revealed that the addition of chitin whiskers into the nanocomposite hydrogels markedly promoted the cell adhesion and proliferation of the osteoblast cells. The biocompatible nanocomposite hydrogels have potential application in bone tissue engineering

Rubbery Chitosan/Carrageenan Hydrogels Constructed through an Electroneutrality System and Their Potential Application as Cartilage Scaffolds

In the present work, the bulk and homogeneous composite hydrogels were successfully constructed from positively charged chitosan (CS) and negatively charged carrageenan (CG) in alkali/urea aqueous solution via a simple one-step approach for the first time. An electroneutral CS solution was achieved in alkali/urea, leading to a homogeneous solution blended by CS and CG, which could not be realized in acidic medium because of the agglomeration caused by polycation and polyanion. Subsequently, the CS/CG composite hydrogels with multiple cross-linked networks were prepared from blend solution by using epichlorohydrin (ECH) as the cross-linking agent. The composite hydrogels exhibited hierarchically porous architecture, excellent mechanical properties as well as pH- and salt-responsiveness. Importantly, the composite hydrogels were successfully applied for spreading ATDC5 cells, showing high attachment and proliferation of cells. The results of fluorescent micrographs and scanning electronic microscope images revealed that the CS/CG composite hydrogels enhanced the adhesion and viability of ATDC5 cells. The alcian blue staining, glycosaminoglycan quantification, and real-time PCR analysis proved that the CS/CG composite hydrogels could induce chondrogenic differentiation of ATDC5 cells in vitro, exhibiting great potential for application in cartilage repair. This work provides a facile and fast fabrication pathway for the construction of ampholytic hydrogel from polycation and polyanion in an electroneutrality system