Delivery of Alpha-Ketoglutarate from Hyaluronic Acid Hydrogels for Bone Repair Applications

Bone loss affects millions of people every year posing a major public health problem. Currently, autograft and allograft bones are the only options for treating bone loss. Although, they pose many limitations including donor availability, immunogenicity risks, and the potential to carry a risk of disease and/or infection transmission to name a few. Therefore, there is a pressing clinical need to create a novel treatment that will promote bone repair. Alpha-ketoglutarate (aKG) was investigated as it plays an important role in cellular energy metabolism as a key intermediate in the Krebs cycle. It has been shown to stimulate the production of collagen in the bone repair process. However, controlling the release of aKG is important in being able to control where and how much new bone growth is stimulated. To address this aKG was delivered via a hyaluronic acid hydrogel and its release was controlled via the degradation of poly(alpha-ketoglutarate) microparticles (paKG MPs). paKG MPs were synthesized and characterized based on size, shape, and uniformity. The release of aKG from paKG MPs was evaluated, as well as the addition of paKG MPs into norbornene functionalized hyaluronic acid and maleimide functionalized hyaluronic acid hydrogels. Initial cell work was also done to grow osteoblasts for future work. It was found that paKG MPs were of the desired size and shape. The release of aKG from the paKG MPs was found to be sustained. The addition of paKG MPs in norbornene functionalized hyaluronic acid (NorHA) was found to be ineffective due to the opaqueness of the MPs. Maleimide functionalized hyaluronic acid (MaHA) hydrogels were chosen as an alternative delivery system for this reason. Future tests will be done on the addition of paKG MPs into MaHA hydrogels. Osteoblasts were also successfully grown and will be used in future studies.