NSF Award
1752915
Bone grafts are commonly used to treat bone defects and enhance fracture repair. Bone tissue grafts taken from the patient -- autografts -- are the gold standard, but require a second surgery and are limited in volume. Allografts, taken from a cadaver, have a fairly high failure rate after 10 years. Tissue engineered bone grafts hold promise, but have seen limited success due to the need of bone cells to see mechanical loading during the development and healing process in order to grow properly. This research project investigates the combination of hydrogels to encapsulate bone cells with low intensity pulsed ultrasound to provide controlled mechanical stimulation in order to enhance bone tissue development. The optimum combination of hydrogel stiffness and acoustic radiation force level is being determined first, and then the system is being tested in mice to determine whether or not it is effective for treating a bony defect when the ultrasound is applied through the skin. The project integrates students from high school through graduate and medical school into the research effort and introduces new course content into a biomaterials class. <br/><br/>The objectives of this research project are to evaluate the impact in vitro of RGD-modified alginate hydrogel stiffness and low-intensity pulsed ultrasound derived acoustic radiation force on encapsulated osteoblast behavior and to assess the efficacy, in vivo, of transdermally applied acoustic radiation force on osteoblasts encapsulated in an RGD-modified alginate hydrogel and implanted into a mouse cranial defect. Combinations of hydrogel stiffness and acoustic radiation force levels are being investigated to determine the optimum levels for upregulating phenotypic markers and mineralization of the encapsulated osteoblasts. The optimum system is then being utilized in a mouse cranial defect model, with ultrasound force applied daily for 20 minutes a four-week period. The healing of the construct is being evaluated through histology and histomorphometry.
