October 25th CTE Seminar

Title: Investigation of Keratin and Keratin-Containing Composite Biomaterials: Applications
in Peripheral Nerve Regeneration

Presenter: Dr. Nils Potter, Department of Biomedical Engineering

Research group: Nanostructured Biopolymer Engineering Lab

Keratins are a family of structural proteins that can be extracted from wool, skin, nails, and hair, and have been investigated in the field of tissue regeneration. Humans make several types of keratins, so it has a natural acceptance by the body; however, keratins can be hard to process into useful products. This work sought to explore a production method that addresses the problem of protein aggregation during purification. Experiments comparing preparation methods that maximize and minimize protein aggregation were compared. Data showed that minimizing aggregation leads to better biomaterial characteristics; however, even after optimization of purification, keratins still have limitations. A typical approach to address this in other systems has been by blending. In the present work, we explored a blend made from keratin and type 1 collagen. A method was developed to effectively blend keratin and collagen. Data showed intimate mixing of the two proteins was achieved, and resulting characteristics were improved compared to either pure material. Finally, studies were conducted to assess the potential for these blends to be used as conduit luminal fillers to regenerate injured nerves. In the present study, we investigated the behavior the Schwann cell to attach, move and grow through a keratin/collagen biomaterial. Data showed good cell behavior, suggesting the material could be used in a medical product for nerve repair.

Title: Investigating the Oncological and Immunological Effects of Histotripsy

Presenter: Alissa Hendricks, Department of Biomedical Engineering

Research groups: Therapeutic Ultrasound Lab

Cancer is the second leading cause of death worldwide, and with an ageing population the incidence is increasing. To address this need, histotripsy has been developed as a non-invasive, non -thermal, non-ionizing ablation method that utilizes focused ultrasound to homogenize targeted tissue with millimeter precision. Previous work has established that histotripsy is capable of specifically ablating tissues based on mechanical properties, and other work indicates an immunomodulatory aspect as well. For this work we have established a new porcine xenograft model for studying tumor ablations in a scale and environment more comparable to humans. This model has promise to support the growth of human xenograft tumors at a steady growth rate, has comparable histological morphologies to existing models and de novo tumors, and has easy to replicate features. In addition, we investigated the efficacy of histotripsy in treating cancer through a murine model for which we used custom built systems that included an automated treatment system to increase treatment reproducibility. We performed an in vivo experiment using a 1 MHz small animal transducer for the volumetric ablation of pancreatic tumors in 4T1 and Pan02 mouse models. Results showed that we were able to successfully generate cavitation and achieve well- defined ablation zones within the murine pancreatic tumors. Tumor size decreased for every mouse that had been treated with histotripsy, with a significant difference between treated- untreated tumor diameters one day post-treatment. Treated Pan02-tumor animals saw an increase of 16 days of progression free survival and 7 days overall survival. To more precisely analyze the effects of the immune response, we have established an in vitro model using the 4T1 and Pan02 cell lines that have been transfected to produce a specific protein for controlled antigen presentation. We have found that histotripsy is able to release damage associated molecular patterns and our specific antigen from within the cell. In the future, we will establish the immunological response to the released antigens. Overall, the results of this study suggest that histotripsy has the potential to become a novel non-invasive therapy method for the treatment of malignant tumors.