Biomedical Application of Hyaluronic Acid Nanoparticles

Hyaluronic acid (HA) is a naturally occurring biodegradable polymer with a variety of applications in medicine including tissue engineering, dermatological fillers, and viscosupplementation for osteoarthritis treatment. The cytotoxicity of crosslinking techniques for scaffold fabrication and the high viscosity of viscosupplements have been issues impeding the development of products from HA. Thus, novel HA biomaterials for tissue engineering and improved properties of viscosupplements are in demand. Nanotechnology can be a useful tool to address these needs. The aim of this dissertation was to synthesize HA nanoparticles and use the fabricated nanoparticles to develop colloidal systems for these proposed biomedical applications. First, nanoparticles were successfully synthesized using a technique free of an oil and surfactant. Nanoparticles then were employed to develop colloidal gels and suspensions. Several methods were used to characterize nanoparticles, colloidal gels, and colloidal suspensions including dynamic light scattering, uniaxial compression testing, and rheometry. Factors such as polymer type, concentration of polymer, and molecular weight of polymer (17, 741, and 1500 kDa) influenced nanoparticle properties. In addition, mixing nanoparticles composed of 17 kDa HA in deionized water at different concentrations (15%, 30%, and 45% w/v) formed a stable 3-D colloidal gel as a result of physical entanglement of free polymer chains on the surfaces of nanoparticles. Mechanical and rheological investigation showed that Young's modulus, shear modulus, viscosity, and viscoelasticity of colloidal gels are concentration dependent. These investigations also indicated that the colloidal gels had recoverable and dynamic properties. Viscous suspensions were also formed via addition of nanoparticles (17kDa or 1500 kDa) to either deionized water or to hyaluronic acid solution (1500 kDa). Rheological investigations showed that the viscosity IV and the viscoelasticity of the suspensions can be controlled via interactions between polymer in solution and free polymer chains on the surfaces of nanoparticles. These interactions were shown to be influenced by type of the nanoparticles (17 kDa or 1500 kDa). Overall, a variety of HA nanoparticle formulations were discovered that enable new strategies in tissue scaffolding, dermatological filling, and viscosupplementation.