387005 Engineering Biomimetic Cues to Restore Musculoskeletal Tissue Function

Sunday, November 16, 2014
Galleria Exhibit Hall (Hilton Atlanta)
Julianne L. Holloway, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA

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, integrates poorly with surrounding tissue, 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 anisotropic mechanical properties of the native meniscus. The hydrogel composite was characterized in compression (0.1 - 0.8 MPa) and tension (0.1 - 250 MPa) for a number 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, where grafting resulted in a 20-fold improvement to interfacial shear strength. Following implantation into human cadaveric knees, ex vivo gait simulations showed improved contact areas and stresses along the tibial plateau for the hydrogel composites in comparison to a meniscectomy.

Currently, I am a postdoctoral fellow in Jason Burdick’s laboratory researching synergistic growth factor delivery for improved osteogenesis using proteolytically degradable hydrogels. A critical-sized calvarial defect was used to determine the effect of combined SDF-1α, a known chemokine, and BMP-2 delivery on bone formation in vivo. The treatment group with combined delivery showed significantly higher bone formation when compared to hydrogels loaded with either growth factor alone or the empty defect group. More importantly, SDF-1α, when delivered in combination with BMP-2, effectively reduced the required BMP-2 dose for similar bone formation by increasing cellular invasion into the defect site. Ongoing work evaluating the activation of other osteogenic signaling pathways is being investigated to further improve BMP-induced osteogenesis.

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, structural, and biological signals needed for function in musculoskeletal tissues.

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