(4bb) Replicating Signaling Cues to Restore Musculoskeletal Tissue Function Using Hydrogel-Based Materials

Musculoskeletal injuries and diseases, which include meniscal tears and degenerative disc disease, are a significant health concern in the United States. Current treatments, however, typically rely on donor tissues (either allo- or autografts) and suffer from poor availability. Furthermore, donor tissue does not always adequately restore function (meniscus allografts), integrates poorly with surrounding tissue (bone grafts), and can have a high morbidity. Tissue engineering aimed at replicating and/or restoring the biological and mechanical cues required for tissue function offers an advantage to current treatments and prevents further musculoskeletal degeneration. My research has focused on the intelligent design of hydrogels towards this aim.

During my Ph.D., under the advisement of Anthony Lowman and Giuseppe Palmese, I developed and characterized a fiber-reinforced hydrogel composite for meniscal replacement aimed at replicating the mechanical properties of the native meniscus. The hydrogel composite was characterized in compression (0.1 - 0.8 MPa) and tension (0.1 - 250 MPa) over a wide range of formulations demonstrating fine control over mechanical properties within the range of the human meniscus. Furthermore, the fiber-hydrogel interface was tailored for optimal adhesion using a novel biocompatible grafting technique to form a direct covalent linkage between the fiber and hydrogel. Grafting resulted in significant improvements to interfacial shear strength from 11 kPa without any treatment to above 220 kPa following grafting.

Currently, I am a postdoctoral fellow in Jason Burdick’s laboratory researching synergistic growth factor delivery for improved osteogenesis using proteolytically degradable hydrogels. In vitro cell migration assays indicate stromal cell-derived factor-1 alpha (SDF-1α) significantly increases human mesenchymal stem cell chemotaxis. This motivates the use of SDF-1α to recruit stem cells in conjunction with more traditional osteogenic growth factors (i.e. bone morphogenic proteins (BMPs)) in the development of therapies for improved tissue repair. Ongoing work is evaluating the synergistic effect of SDF-1α and BMP on osteogenesis in an in vivo rat cranial defect model.

In the future as a faculty member, I will use my experience with and knowledge of polymer science, biomechanics, and growth factor signaling to develop finely tunable materials that replicate and restore the mechanical and biological signals needed for function in musculoskeletal tissues.