Scaffold-free facial nerve conduit engineered using dental pulp stem cells
Matthew T. Dailey is currently a PGY-2 resident in the 6 year M.D. Oral and Maxillofacial Surgery program at the University of Pittsburgh, Pittsburgh, PA. He obtained his DDS from the University of California, Los Angeles in 2013. Following graduation, Dr. Dailey entered the U.S. Air Force, completed a 1 year Advanced Education in General Dentistry residency and served an additional three years as a general dentist. Dr. Dailey’s research interests pertain to the use of dental pulp cells for craniofacial tissue engineering.
The goal of this study is to improve care for treating facial nerve injuries. Facial nerve defects may result from trauma, tumor ablation, and iatrogenic surgical injury. The current gold standard for peripheral nerve repair is to replace damaged tissue with an autograft, however cable grafting comes with slow or incomplete recovery of volitional movement. One factor contributing to these results is diminished Schwann cell support. Schwann cells provide neurotrophic factors (NTFs), which are known to promote neuron survival and axon extension. The dental pulp contains a population of stem/progenitor cells that are being investigated for several clinical applications. These dental pulp cells (DPCs) have been shown to endogenously express high levels of NTFs, a characteristic likely due to their neural crest origins. Cell sheets are a form of scaffold- free tissue engineering where cells proliferate to confluence and produce endogenous extracellular matrix (ECM) to form a layer of tissue that can be separated from the substrate. The ECM within these cell sheets would provide a substrate to enable axon growth and extension. We hypothesize that scaffold-free DPC sheets will 1- provide continuous delivery of NTFs to promote axon regeneration and 2- provide an ECM substrate that will support axon growth. In this study we are evaluating the functional effect of DPC sheets on neurons in vitro. Then we will be assembling our DPC sheets into solid, cylindrical constructs and using them to bridge segmental defects in the rat facial nerve. We will be determining the ability of these scaffold-free DPC constructs to restore motor nerve function in vivo. This project will provide foundational information on engineering a biological nerve conduit that provides both the trophic cues needed to promote axon regeneration and also and ECM that will support axon extension. The success of these studies will lead to a novel and feasible method for facial nerve regeneration.