Peripheral nerve injuries are damaging nerve conditions that can result in pain and motor and sensory deficits. A number of biological processes, including structural, transcriptional, translational and growth-related pathways within nerve cells are affected by injury. In this study, we examine a peripheral nerve injury to compare protein expression level changes among control uninjured nerves and two different injury repair strategies at an early regenerative time point; such changes may be useful in predicting the eventual success of a particular repair strategy. UPLC-ESI mass spectrometry and MaxQuant LFQ and PEAKS v8.5 bioinformatic algorithms were performed on samples from the proximal stump of peripheral nerves injured and acutely repaired by autograft or a new nerve lengthening strategy, as well as uninjured contralateral control nerves. The proteins overexpressed in the lengthened sample by two-fold or greater were analyzed in DAVID, and the output data was manually clustered into 15 pathways relevant to nerve injury and regenerative processes. We present evidence of upregulated structural, immune response, bioenergetic, and protein synthesis pathways in the lengthened condition to support the stretch-activated growth hypothesis for nerves. We also highlight candidate proteins for future diagnostic or manipulation studies to characterize the nerve regeneration environment. These findings are important in advancing our understanding of the peripheral nerve regeneration process post-injury.

in progress

Traumatic brain injury (TBI) is a common clinical condition in which the brain is subject to a mechanical injury. This results in short- and long-term clinical symptoms and also increases the risk for future neurodegeneration. Previous studies trying to link TBI with its long-term outcomes have only been performed on animal or culture cell models, but very few studies have been performed on 3D human cellular models. These limitations are major barriers for current translation of preclinical science to clinical implementation. Recent studies suggest that 3D brain organoids may be a useful model to study links between TBI and downstream adverse effects. Previous experiments suggest that injuring organoids one at a time through the use of a modified mouse CCI impactor is tedious and creates high variability. In this thesis study, a novel brain organoid impact device was designed, manufactured, and tested to effectively model TBI in a human system. Through phantom organoid and human organoid testing, the impact device demonstrated a more simple, accurate, and efficient model to injure brain organoids, compared to its predecessors. The device allows for simultaneous injury of multiple organoids, consistent and controlled deformation of organoids, and the ability to vary impact force and velocity, based on gravity and the defined compression of a spring. This study represents a dramatic improvement over previous TBI organoid models, and will enable us to better understand downstream effects TBI towards improve translation between preclinical and clinical models. It is anticipated that this device will support a variety of experiments to evaluate TBI related diagnostics, therapeutics, biomarkers, and mechanisms of disease progression.

The Dorsal Root Ganglion (DRG) cell culture model is a powerful and frequently used tool in the field of neurobiology. Its use has profoundly impacted the study of peripheral neuropathies and helped make important discoveries about neural sensitization pathways. However, few studies have comprehensively tested how accurately this in vitro model portrays the distribution and spatial patterning of sensory neurons in vivo. As a first step in making such comparisons, we wanted to comparing their relative distributions of small-type nociceptors (peptidergic and non-peptidergic neurons) in vivo and in vitro. Our data suggest that there are significantly fewer peptidergic and more mixed-identity neurons in culture compared to in DRG cell bodies or in sural (sensory) nerves. Additionally, we discovered an interesting pattern of growth between some peptidergic and non-peptidergic neurons in vitro, whereby they often traveled in pairs, appearing as either a single neuron of mixed identity or two neurons in extremely close proximity with identical trajectories. These results stress the importance of making careful and more refined evaluations of the DRG cell culture model depending on the context of a particular scientific question.

The shoulder is the most unstable joint in the body.1 Decreased stability causes the shoulder to dislocate easily, stretching the joint capsule and glenohumeral ligaments. This increases the likelihood of redislocation. Recurrent dislocations can cause the ligaments and joint capsule to pull on the labrum and create a lesion. Once a lesion is formed the joint is chronically unstable, and must be repaired surgically. The standard method of repair is to arthroscopically implant a suture anchor into the bone, which is then used to secure the soft tissue back onto the bone. This reintroduces tension to the capsule and glenohumeral ligaments, therefore restoring stability to the joint. There are several different types of suture anchors currently available on the market: the rigid knotted anchor, the rigid knotless anchor, and the soft anchor.

This study defines the anatomical and mechanical design constraints of shoulder instability repair by researching the injury mechanism, and benefits and downfalls of the current repair methods. Once these design constraints are well defined, two new suture anchor prototype designs are then proposed. Design 1 is a hybrid between a rigid and soft anchor, starting with the design for the current soft anchor, but creating wings from Nitinol, rather than using the sleeve to anchor the device. Design 2 starts with the soft anchor design, but adds a bone barrier to protect the bone from the micro-motion of the anchor.

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