Silk fibroin hydrogels and films for neurological applications

Silk fibroin is a unique biomaterial that can be processed into numerous different physical states, that can be used for applications such as drug delivery, tissue engineering, and optics. This thesis explored two new neurological applications for silk fibroin biomaterials that could lead to significant advancements in drug / gene delivery and in vitro models of brain injury.;First, silk fibroin hydrogels were optimized to create a biomimetic brain phantom in a traumatic brain injury model using a mixture of silk fibroin hydrogels and 200μm silk fibroin fibers. These hydrogels were able to mimic the biomechanical properties of mouse and rat cortical tissue in confined compression (∼50 kPa), and were able to match the rheological properties (dynamic viscosity and dynamic shear modulus) of these cortical tissues within the physiological range for traumatic brain injury (∼20 kPa in the range of 60-100 rad/s). In addition, these hydrogels exhibited the same diffusivity properties as cortical tissue. Cell encapsulation studies were also briefly explored and showed promising initial results.;Second, silk fibroin films were explored for their drug and gene delivery capabilities. Therapeutic necrostatins were loaded into silk fibroin films and delivered to the mouse cortex in a controlled cortical impact traumatic brain injury model to explore the ability to inhibit injury-induced necroptosis. Additionally, adeno-associated viral vectors were loaded into similar silk films and delivered to the cortex of mice to explore transduction of sub-dural cortical neurons, and dural fibroblasts for potential disease model targets such as meningioma.