Dissertation Defense (IPN): Dylan Scarton

Neuroscience Doctoral Candidate Dylan Scarton 
Dissertation title: Designer DX-tile DNA hydrogels for peripheral nerve regeneration
Dissertation Advisor: Remi Veneziano, PhD, Department of Bioengineering

Abstract: Peripheral nerve injury (PNI) represents a significant clinical problem worldwide, with more than 100,000 peripheral nerve repairs performed annually in the United States alone. The challenge of treating PNIs is primarily due to the complexity of their tissue architecture and the overall organization of the peripheral nervous system, which has a limited regenerative capacity. Therefore, developing novel strategies to promote the efficient regeneration of peripheral nerves could improve the lives of millions of individuals suffering from PNI-related disabilities and thus reduce the burden on the healthcare system. To address this challenge, I developed a hybrid biomaterial that can revolutionize the design of tissue engineering scaffolds for peripheral nerve repair and other soft tissues. I synthesized pure deoxyribonucleic acid (DNA) hydrogels and doped them with conductive polymers so that they can be tuned to match the elastic moduli and electrical conductivity of native peripheral nerve tissue. I leveraged the assembly precision and conjugation ease of DNA biomaterials to incorporate adhesion molecules capable of facilitating neuronal cell adhesion and created a soluble gradient of neurotrophic factors (NFs) to promote and guide outgrowth capable of mimicking the proximal and distal gradients that occur in peripheral nerve regeneration. Finally, I integrated these fully loaded hydrogels into a three-dimensional (3D)-printed collagen nerve guidance conduit and assessed their performance towards future studies of nerve regeneration and repair in a rodent sciatic nerve injury model. This work helps to define a set of design rules that could inform future scaffold schemes for nervous tissue engineering and the treatment of severe PNIs by better understanding its formation and physiology, thereby introducing a new paradigm in convergent fields from DNA nanotechnology to regenerative medicine.