Hettiaratchi, MarianSpaulding, Veronica,Johnson, Ireland2022-07-122022-07-122022https://hdl.handle.net/1794/27340Large bone defects and fractures caused by trauma or disease remain a serious challenge for orthopedic surgeons, and there is a need for more effective treatment strategies to repair injured bone. Bone autografts, a tissue graft from the same patient, are the ideal treatment strategy because there is a low chance of host rejection, and the graft is not weakened from sterilization. However, bone autografts are not widely available, and their harvest can cause donor site morbidity. As an alternative strategy, biomaterials composed of the natural polymer hyaluronic acid (HA) can be used to deliver osteogenic (bone-forming) proteins that repair injured bone. The objective of this study was to develop and test the biocompatibility of HA-based hydrogels for protein delivery for bone regeneration applications. HA hydrogels were formed by dynamic, covalent bonds between aldehyde functional groups on oxidized HA and HA functionalized with adipic acid hydrazide or carbohydrazide groups. Hydrogels were seeded with 3T3 fibroblast cells expressing green fluorescent protein to evaluate cell compatibility. Live and dead cells were evaluated using green fluorescence from GFP and red fluorescence from ethidium homodimer, respectively. A combination of HA separately modified with oxidized and carbohydrazide HA, each at 2.5% (w/v), maintained high cell viability (>82.3% for all time points) and encouraged a rate of cell growth that surpassed all other conditions. This project also investigates the cytocompatibility of the HA hydrogels with skeletal myoblasts. Future work will aim to further functionalize and optimize the HA hydrogels themselves as a protein delivery vehicle for osteogenic proteins like BMP-2. The impact of this project will facilitate the future use of HA hydrogels as a biomaterial that rivals the healing response of bone autografts.en-USCC BY-NC-ND 4.0hydrogelboneregenerationmedicineHyaluronic acidThesis/Dissertation0000-0002-5223-3426