Nanoparticle-Induced Controlled Drug Delivery Using Chitosan-Based Hydrogel and Scaffold: Application to Bone Regeneration

The novel chitosan nanohybrid hydrogel and scaffold have been developed with high mechanical strength and tailor the drug release ability for their applications in the biomedical arena. Nanohybrid hydrogels are prepared in dilute acetic acid medium using two different types of two-dimensional-layered nanoparticles. Scaffolds are prepared through lyophilization of hydrogels. Highly porous, open, and 3D interconnected morphologies are observed in the nanohybrid scaffolds, as opposed to the thick wall, smaller pore dimension in pure chitosan. The interaction between the nanoparticles and chitosan chains are elucidated using different spectroscopic techniques, which in turn are responsible for the uniform distribution of the nanoparticle in the chitosan matrix. Nanohybrids are found to be highly mechanically stable in both states (hydrogel and scaffold), as compared to pure chitosan because of the good reinforcing ability of 2D nanoparticles. Sustained drug release has been achieved in nanohybrid in vitro, as compared to the pure chitosan hydrogel/scaffold, mainly due to greater interactions between the components and the better barrier effect of 2D nanoparticles. Cytotoxicity of the nanohybrids is verified using NIH 3T3 mouse embryonic fibroblast cells for their possible use as controlled drug delivery vehicles. Nanohybrids are found to be nontoxic in nature and more biocompatible as compared to pure chitosan, as observed through cell viability and cell imaging studies. Interestingly, cell growth occurs within the pores of the nanohybrid scaffold, vis-a-vis the surface proliferation noticed in the pure chitosan scaffold. Better biocompatibility, hydrophilic nature, and sustained delivery with location specific cell growth make this nanohybrid hydrogel unique for biomedical uses. The bone regeneration rate is found to be significantly higher for the nanohybrid scaffold as compared to blank/pure chitosan without any side effect, suggesting nanohybrid systems are superior biomaterials.