A simple method to rapidly assess the tibial tuberosity-trochlear groove distance using computed tomography.

BACKGROUND: The tibial tuberosity-trochlear groove (TTTG) distance is used to assess patellofemoral instability (PFI) and the likelihood of the development of patellofemoral disorders. The current gold standard in the assessment of the TTTG is computed tomography (CT) or magnetic resonance imaging (MRI). The current image software used for viewing these CT images does not allow for easy assessment of the TTTG. AIMS: This study presents a simple method to measure the TTTG on any image software, utilizing easily available and affordable stationary. METHODS: Four consecutive patients with no known knee pathologies were selected from recent studies at our institution. Their TTTGs were measured using this study's method and validated using the standard, freely available image analysis software Fiji. Pre-defined anatomical landmarks were located and marked using adhesive pieces of paper. The TTTG was defined as the distance between parallel lines through the apex of the tibial tuberosity and trough of the trochlear groove, where each of these lines is perpendicular to the Dorsal Condylar Line. RESULTS: The TTTG measured using this study's method was found to be in agreement with the measurements made using Fiji software. CONCLUSIONS: This study demonstrates that the TTTG can be simply and quickly assessed using readily available and affordable stationery, without the need for expensive or complex secondary analysis software. This could allow for the assessment of PFI in the outpatient clinic whilst the patient is present, offering valuable assistance to the orthopaedic surgeon in clinical decision making.

Multi-factorial nerve guidance conduit engineering improves outcomes in inflammation, angiogenesis and large defect nerve repair.

Nerve guidance conduits (NGCs) are sub-optimal for long-distance injuries with inflammation and poor vascularization related to poor axonal repair. This study used a multi-factorial approach to create an optimized biomaterial NGC to address each of these issues. Through stepwise optimization, a collagen-chondroitin-6-sulfate (Coll-CS) biomaterial was functionalized with extracellular matrix (ECM) components; fibronectin, laminin 1 and laminin 2 (FibL1L2) in specific ratios. A snap-cooled freeze-drying process was then developed with optimal pore architecture and alignment to guide axonal bridging. Culture of adult rat dorsal root ganglia on NGCs demonstrated significant improvements in inflammation, neurogenesis and angiogenesis in the specific Fib:L1:L2 ratio of 1:4:1. In clinically relevant, large 15 mm rat sciatic nerve defects, FibL1L2-NGCs demonstrated significant improvements in axonal density and angiogenesis compared to unmodified NGCs with functional equivalence to autografts. Therefore, a multiparameter ECM-driven strategy can significantly improve axonal repair across large defects, without exogenous cells or growth factors.

The Use of Genipin as an Effective, Biocompatible, Anti-Inflammatory Cross-Linking Method for Nerve Guidance Conduits.

A number of natural polymer biomaterial-based nerve guidance conduits (NGCs) are developed to facilitate repair of peripheral nerve injuries. Cross-linking ensures mechanical integrity and desired degradation properties of the NGCs; however, common methods such as formaldehyde are associated with cellular toxicity. Hence, there is an unmet clinical need for alternative nontoxic cross-linking agents. In this study, collagen-based NGCs with a collagen/chondroitin sulfate luminal filler are used to study the effect of cross-linking on mechanical and structural properties, degradation, biocompatibility, and immunological response. A simplified manufacturing method of genipin cross-linking is developed, by incorporating genipin into solution prior to freeze-drying the NGCs. This leads to successful cross-linking as demonstrated by higher cross-linking degree and similar tensile strength of genipin cross-linked conduits compared to formaldehyde cross-linked conduits. Genipin cross-linking also preserves NGC macro and microstructure as observed through scanning electron microscopy and spectral analysis. Most importantly, in vitro cell studies show that genipin, unlike the formaldehyde cross-linked conduits, supports the viability of Schwann cells. Moreover, genipin cross-linked conduits direct macrophages away from a pro-inflammatory and toward a pro-repair state. Overall, genipin is demonstrated to be an effective, safe, biocompatible, and anti-inflammatory alternative to formaldehyde for cross-linking clinical grade NGCs.

Controlling the dose-dependent, synergistic and temporal effects of NGF and GDNF by encapsulation in PLGA microparticles for use in nerve guidance conduits for the repair of large peripheral nerve defects.

Neurotrophic factor delivery via biodegradable nerve guidance conduits may serve as a promising treatment for the repair of large peripheral nerve defects. However, a platform for controlled delivery is required because of their short in vivo half-life and their potential to impede axonal regeneration when used in supraphysiological doses. In this study, we investigated the dose-dependent, synergistic and temporal effects of NGF and GDNF on neurite outgrowth, adult dorsal root ganglia axonal outgrowth, Schwann cell migration and cytokine production in vitro. Using the optimal dose and combination of NGF and GDNF, we developed a PLGA microparticle-based delivery platform to control their delivery. The dose-dependent effects of both NGF and GDNF individually were found to be non-linear with a saturation point. However, the synergistic effect between NGF and GDNF was found to outweigh their dose-dependent effects in terms of enhancing Schwann cell migration and axonal outgrowth while allowing a 100-fold reduction in dose. Moreover, a temporal profile that mimics the physiological flux of NGF and GDNF in response to injury, compared to one that resembles an early burst release delivery profile, was found to enhance their bioactivity. The optimized NGF- and GDNF-loaded microparticles were then incorporated into a guidance conduit, and their capacity to enhance nerve regeneration across a 15 mm sciatic nerve defect in rats was demonstrated. Enhanced nerve regeneration was seen in comparison to non-treated defects and very encouragingly, to a similar level compared to the clinical gold standard of autograft. Taken together, we suggest that this delivery platform might have significant potential in the field of peripheral nerve repair; allowing spatial and temporal control over the delivery of potent neurotrophic factors to enhance the regenerative capacity of biomaterials-based nerve guidance conduits.

Reduced Frequency of Ipsilateral Express Saccades in Cervical Dystonia: Probing the Nigro-Tectal Pathway.

Background: Cervical dystonia is a hyperkinetic movement disorder of unknown cause. Symptoms of cervical dystonia have been induced in animals in which the integrity of the nigro-tectal pathway is disrupted, resulting in reduced inhibition of the deep layers of the superior colliculus. This same pathway is believed to play a critical role in saccade generation, particularly visually guided, express saccades. It was hypothesized that individuals with cervical dystonia would present with a higher frequency of express saccades and more directional errors. Methods: Eight individuals with cervical dystonia and 11 age- and sex-matched control participants performed three saccadic paradigms: pro-saccade, gap, and anti-saccade (120 trials per task). Eye movements were recorded using electro-oculography. Results: Mean saccadic reaction times were slower in the cervical dystonia group (only statistically significant in the anti-saccade task, F(1, 35)  =  4.76, p  =  0.036); participants with cervical dystonia produced fewer directional errors (mean 14% vs. 22%) in the anti-saccade task; and had similar frequencies of express saccades in the gap task relative to our control population (chi-square  =  1.13, p  =  0.287). All cervical dystonia participants had lower frequencies of express saccades ipsilateral to their dystonic side (the side to which their head turns), (chi-square  =  3.57, p  =  0.059). Discussion: The finding of slower saccadic reaction times in cervical dystonia does not support the concept of reduced inhibition in the nigro-tectal pathway. Further research is required to confirm the observed relationship between the lateralization of lower frequencies of express saccades and direction of head rotation in cervical dystonia.