Study on tracheal collapsibility, compliance, and stress by considering nonlinear mechanical property of cartilage

Tracheal cartilage has been widely regarded as a linear elastic material either in experimental studies or in analytic and numerical models. However, it has been recently demonstrated that, like other fiber-oriented biological tissues, tracheal cartilage is a nonlinear material, which displays higher strength in compression than in extension. Considering the nonlinearity requires a more complex theoretical frame work and costs more to simulate. This study aims to quantify the deviation due to the simplified treatment of the tracheal cartilage as a linear material. It also evaluates the improved accuracy gained by considering the nonlinearity. Pig tracheal rings were used to exam the mechanical properties of cartilage and muscular membrane. By taking into account the asymmetric shape of tracheal cartilage, the collapse behavior of complete rings was simulated, and the compliance of airway and stress in the muscular membrane were discussed. The results obtained were compared with those assuming linear mechanical properties. The following results were found: (1) Models based on both types of material properties give a small difference in representing collapse behavior; (2) regarding compliance, the relative difference is big, ranging from 10 to 40% under negative pressure conditions; and (3) the difference in determining stress in the muscular membrane is small too: <5%. In conclusion, treating tracheal cartilage as a linear material will not cause big deviations in representing the collapse behavior, and mechanical stress in the muscular part, but it will induce a big deviation in predicting the compliance, particularly when the transmural pressure is lower than -0.5 kPa. The results obtained in this study may be useful in both understanding the collapse behavior of trachea and in evaluating the error induced by the simplification of treating the tracheal cartilage as a linear elastic material.

Nonlinear mechanical property of tracheal cartilage: A theoretical and experimental study

Background: Despite being the stiffest airway of the bronchial tree, the trachea undergoes significant deformation due to intrathoracic pressure during breathing. The mechanical properties of the trachea affect the flow in the airway and may contribute to the biological function of the lung. Method: A Fung-type strain energy density function was used to investigate the nonlinear mechanical behavior of tracheal cartilage. A bending test on pig tracheal cartilage was performed and a mathematical model for analyzing the deformation of tracheal cartilage was developed. The constants included in the strain energy density function were determined by fitting the experimental data. Result: The experimental data show that tracheal cartilage is a nonlinear material displaying higher strength in compression than in tension. When the compression forces varied from -0.02 to -0.03 N and from -0.03 to -0.04 N, the deformation ratios were 11.03±2.18% and 7.27±1.59%, respectively. Both were much smaller than the deformation ratios (20.01±4.49%) under tension forces of 0.02 to 0.01 N. The Fung-type strain energy density function can capture this nonlinear behavior very well, whilst the linear stress-strain relation cannot. It underestimates the stability of trachea by exaggerating the displacement in compression. This study may improve our understanding of the nonlinear behavior of tracheal cartilage and it may be useful for the future study on tracheal collapse behavior under physiological and pathological conditions.

Exploring methods of preparing functional cartilage-bone xenografts for joint repair

This thesis explores the feasibility of donor-receiver concept for joint replacement where cartilage-bone tissues can be taken from either human or other mammals and prepared scientifically for repairing focal joint defects in knees, hips and shoulders. The manufactured construct is immunologically inert and is capable of acting as a scaffold for engineering new cartilage-bone laminates when placed in the joint. Innovative manufacturing procedures and assessment techniques were developed for appraising this tissue-based scaffold. This research has demonstrated that tissue replacement technology can be applied in situations where blood vessels are absent such as in articular cartilage.

Design and characterisation of scaffolds for osteochondral regeneration

Treatment of joint diseases such as osteoarthritis is difficult and requires extensive developments for adequate solutions to emerge. Continued innovation in projects explored in this thesis may be beneficial to understanding the requirements of the joint environment. This may then lead to constructs that perform desirably from both mechanical and biological standpoints, resulting in complete, tissue-engineered osteochondral solutions. This thesis investigated specific scaffold designs for bone and osteochondral tissue engineering, as well as the formation of complex criteria on which cartilage hydrogel scaffolds may be assessed. The combination of hydrogels and ceramics were found to maintain chondrogenesis, while the concentration of photoinitiators in photocrosslinkable hydrogel systems may be optimised to maximise mechanical properties and cell viability. Finally, viscoelasticity of hydrogel blends was assessed using oscillatory motion, demonstrating the property is tailorable.

Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases

Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62x10(-)(9)-1.01x10(-)(1)(2)). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06-1.55, p = 8.9x10(-)(3)). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4x10(-)(8)(8)]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.

Shift in disease burden from communicable to non-communicable diseases: Aiming to achieve Universal Health Coverage in Nepal

A major barrier to accessing healthcare services is spending, and the extended time that non-communicable diseases require treatment for means that many people around the world do not have proper access to care. Saval Khanal from Sankalpa Foundation, Nepal, Lennert Veerman and Samantha Hollingworth from the University of Queensland and Lisa Nissen from Queensland University of Technology lay out the results of their study and establish a method to forecast medicine use in Nepal.

Experimental and numerical investigation of strain-rate-dependent behavior of kangaroo shoulder cartilage

This thesis introduces a new animal model, kangaroo, to biomechanical investigations of shoulder cartilage research. It examines the effect of cartilage structure and constituents on tissue behavior and its adaptation to mechanical loading. In doing so, the study explains the relationship of tissue's functional behaviors to its structure and constituents which has important implications for tissue engineering strategies catering joint specific cartilage tissue generation.

HR-MAS NMR spectroscopy shows regional metabolite variation in bovine articular cartilage

Mechanical stress is an important external factor effecting the development and maintenance of articular cartilage. The metabolite profile of diseased cartilage has been well studied but there is limited information about the variation in metabolite profile of healthy cartilage. With the importance of load in maintaining healthy cartilage, regional differences in metabolite profile associated with differences in load may provide information on how load contributes to the maintenance of healthy cartilage. HR-MAS NMR spectroscopy allows the assessment of tissue samples without modification and was used for assessing the difference in metabolic profile between the load bearing and non-load bearing regions of the bovine articular cartilage. In this preliminary study, we examined cartilage from tibia and femur of four knee joints. Sixteen pairs of 1D-NOESY spectra were acquired. Principle component analysis (PCA) identified chemical shifts responsible for variance. SBASE (AMIX) and the Human Metabolome Database were used in conjunction with previous reported cartilage data for identifying metabolites associated with the PCA results. The major contributors to load-related differences in metabolite profile were N-acetyl groups, lactate and phosphocholine peaks. Integrals of these regions were further analysed using a Student's t-test. In load bearing cartilage regions. N-acetyl groups and phosphocholine were found at significantly higher concentration (p < 0.05 and p < 0.005, respectively) in both femur and tibia, while lactate was reduced in load bearing cartilage (p < 0.005). The results of this pilot HR-MAS NMR study demonstrate its ability to provide useful metabolite information for healthy cartilage.

Risk assessment for airborne infectious diseases between natural ventilation and split-system air conditioner in a university classroom

Indoor air quality is a critical factor in the classroom due to high people concentration in a unique space. Indoor air pollutant might increase the chance of both long and short-term health problems among students and staff, reduce the productivity of teachers and degrade the student’s learning environment and comfort. Adequate air distribution strategies may reduce risk of infection in classroom. So, the purpose of air distribution systems in a classroom is not only to maximize conditions for thermal comfort, but also to remove indoor contaminants. Natural ventilation has the potential to play a significant role in achieving improvements in IAQ. The present study compares the risk of airborne infection between Natural Ventilation (opening windows and doors) and a Split-System Air Conditioner in a university classroom. The Wells-Riley model was used to predict the risk of indoor airborne transmission of infectious diseases such as influenza, measles and tuberculosis. For each case, the air exchange rate was measured using a CO2 tracer gas technique. It was found that opening windows and doors provided an air exchange rate of 2.3 air changes/hour (ACH), while with the Split System it was 0.6 ACH. The risk of airborne infection ranged between 4.24 to 30.86 % when using the Natural Ventilation and between 8.99 to 43.19% when using the Split System. The difference of airborne infection risk between the Split System and the Natural Ventilation ranged from 47 to 56%. Opening windows and doors maximize Natural Ventilation so that the risk of airborne contagion is much lower than with Split System.

The Use of Mesenchymal Stromal Cells in the Treatment of Diseases of the Cornea

As a key component of the ocular surface required for vision, the cornea has been extensively studied as a site for cell and tissue-based therapies. Historically, these treatments have consisted of donor corneal tissue transplants, but cultivated epithelial autografts have become established over the last 15 years as a routine treatment for ocular surface disease. Ultimately, these treatments are performed with the intention of restoring corneal transparency and a smooth ocular surface. The degree of success, however, is often dependent upon the inherent level of corneal inflammation at time of treatment. In this regard, the anti-inflammatory and immuno-modulatory properties of mesenchymal stromal cells (MSC) have drawn attention to these cells as potential therapeutic agents for corneal repair. The origins for MSC-based therapies are founded in part on observations of the recruitment of endogenous bone marrow-derived cells to injured corneas, however, an increasing quantity of data is emerging for MSC administered following their isolation and ex vivo expansion from a variety of tissues including bone marrow, adipose tissue, umbilical cord and dental pulp. In brief, evidence has emerged of cultured MSC, or their secreted products, having a positive impact on corneal wound healing and retention of corneal allografts in animal models. Optimal dosage, route of administration and timing of treatment, however, all remain active areas of investigation. Intriguingly, amidst these studies, have emerged reports of MSC transdifferentiation into corneal cells. Clearest evidence has been obtained with respect to expression of markers associated with the phenotype of corneal stromal cells. In contrast, the evidence for MSC conversion to corneal epithelial cell types remains inconclusive. In any case, the conversion of MSC into corneal cells seems unlikely to be an essential requirement for their clinical use. This field of research has recently become more complicated by reports of MSC-like properties for cultures established from the peripheral corneal stroma (limbal stroma). The relationship and relative value of corneal-MSC compared to traditional sources of MSC such as bone marrow are at present unclear. This chapter is divided into four main parts. After providing a concise overview of corneal structure and function, we will highlight the types of corneal diseases that are likely to benefit from the anti-inflammatory and immuno-modulatory properties of MSC. We will subsequently summarize the evidence supporting the case for MSC-based therapies in the treatment of corneal diseases. In the third section we will review the literature concerning the keratogenic potential of MSC. Finally, we will review the more recent literature indicating the presence of MSC-like cells derived from corneal tissue.