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Background: Self-ligating bracket systems in orthodontics have evolved over the years, but there is limited data regarding their ability to generate torque for efficient third-order tooth positioning. Aim: To compare contemporary active self-ligating bracket systems against a passive self-ligating bracket system and a traditional twin bracket system in their ability to generate torque at different degrees and direction of wire rotation, in vitro. Materials and Methods: Five bracket system groups of 0.022 inch slot size (twin bracket system Victory Series with elastic ligature [E-Vic]; passive self-ligating bracket system Damon Q [P-Dmn]; and active self-ligating bracket systems Speed [A-Spd], InOvation-R [A-Ovn] and Empower 2 Active[A-Emp]) were tested for torque expression utilizing a 0.019 x 0.025 inch stainless steel wire ligated into their slots. Single upper right central incisor brackets of each system were mounted using a specialized mounting jig, and a custom torque assembly fixed to an Instron materials testing machine was utilized to measure torque generated from -15 to +45 degrees of wire rotation. Ten clockwise and ten counterclockwise rotations were performed for each bracket system (n=20). Results: Torque expression significantly varied between bracket systems with P-Dmn, E-Vic and A-Ovn generating the highest torque, and A-Spd and A-Emp the lowest, at most degrees of wire rotation. The direction of wire rotation had the largest effect on the A-Spd and A-Emp active bracket systems, whereby the counterclockwise rotation generated significantly more torque than the clockwise rotation tests. Conclusions: All five bracket systems displayed different behaviors of torque expression when comparing degrees and direction of wire rotation. Understanding these differences in torque expression can help the clinician plan and provide treatment more efficiently.

Harnessing mesenchymal stem cells for tissue repair underpins regenerative medicine. However, how the 3D tissue matrix maintains such cells in a quiescent state whilst at the same time primed to respond to tissue damage remains relatively unknown. Developing more physiologically relevant 3D models would allow us to better understand the matrix drivers and influence on cell-lineage differentiation in situ. In this study, we have developed an ex vivo organotypic rat mandible slice model; a technically defined platform for the culture and characterization of dental pulp progenitor cells expressing GFP driven by the β-actin promoter (cGFP DPPCs). Using confocal microscopy we have characterized how the native environment influences the progenitor cells transplanted into the dental pulp. Injected cGFP-DPPCs were highly viable and furthermore differentially proliferated in unique regions of the mandible slice; in the dentine region, cGFP-DPPCs showed a columnar morphology indicative of expansion and lineage differentiation. Hence, we demonstrated the systematic capacity for establishing a dental pulp cell-micro-community, phenotypically modified in the tooth (the “biology”); and at the same time addressed technical challenges enabling the mandible slice to be accessible on platforms for high-content imaging (the biology in a “multiplex” format).

Trauma to the central and peripheral nervous systems often lead to serious morbidity. Current surgical methods for repairing or replacing such damage have limitations. Tissue engineering offers a potential alternative. Here we show that functionalized α-helical-peptide hydrogels can be used to induce attachment, migration, proliferation and differentiation of murine embryonic neural stem cells (NSCs). Specifically, compared with undecorated gels, those functionalized with Arg-Gly-Asp-Ser (RGDS) peptides increase the proliferative activity of NSCs; promote their directional migration; induce differentiation, with increased expression of microtubule-associated protein-2, and a low expression of glial fibrillary acidic protein; and lead to the formation of larger neurospheres. Electrophysiological measurements from NSCs grown in RGDS-decorated gels indicate developmental progress toward mature neuron-like behavior. Our data indicate that these functional peptide hydrogels may go some way toward overcoming the limitations of current approaches to nerve-tissue repair.

Athletes that participate in contact sport are at risk of suffering Sports-Related Concussion (SRC). A traditional approach of SRC testing relies on the 5th version of the pen-and-paper based sports concussion assessment tool (SCAT5). An open, digital equivalent may facilitate more efficient and transparent assessment. We describe a co-created developed iOS SCAT5 app to enable an Internet of Things (IoT) assessment.

Spinal cord regeneration following injury represents a major clinical challenge. Over recent years, stem cells have demonstrated promise for promoting spinal repair in the lab and in early stage clinical trials through functional replacement of neuronal and glial cells and through secondary trophic mechanisms to promote endogenous regeneration. Research has primarily focused on the use of embryonic tissue-derived stem cells of potentially limited therapeutic application due to related ethical concerns. The dental pulp harbours a source of easily accessible progenitor cells that have demonstrated early promise in improving functional outcome of experimental models of spinal cord injury via growth factor release. This thesis explores the potential of dental pulp progenitor cells (DPPCs) to promote spinal repair through direct cellular replacement. Progenitor cells isolated from murine incisors were found to express early stage neural and glial markers. Specific protocols were developed demonstrating the ability of DPPCs to differentiate in vitro into neuronal-like and oligodendrocyte-like cells with appropriate morphology and expression of mature markers. Electrophysiological testing revealed that DPPC-derived neuronal-like cells were of an immature non-functional phenotype. Undifferentiated DPPCs injected into an ex vivo spinal cord slice model showed signs of proliferation, migration and spontaneous differentiation within spinal tissue. DPPCs pre-differentiated into oligodendrocyte-like cells failed to survive transplantation but neuronally pre-differentiated cells survived, showing signs of integration into endogenous neuronal pathways. In a small scale pilot study, neuronally pre-differentiated DPPCs were transplanted into a clinically relevant in vivo model of spinal cord injury. DPPCs maintained expression of neuronal markers four weeks after grafting into the injured spinal cord. Axonal projections towards grafted cells and synaptic protein expression suggested possible integration into neuronal pathways, albeit without an associated statistical functional improvement. The results presented in this thesis provide a strong case for the potential of DPPCs to facilitate functional recovery through direct cell replacement mechanisms.