Extrusion bioprinting of hydrogel scaffolds: printability and mechanical behavior

Extrusion bioprinting (known as dispensing-based bioprinting as well) has been widely used to extrude or dispense continuous strands or fibers of biomaterials (e.g. hydrogel) and cells (such a mixture is referred to as "bioink"), layer-by-layer, to form three-dimensional (3D) scaffolds for tissue engineering. For extrusion bioprinting, one key issue is printability or the capability to print and maintain reproducible 3D scaffolds from bioink, which is typically measured by the difference in structure between the designed scaffold and the printed one. Due to the structural difference (or the difference caused by printability), the printed scaffold's mechanical properties are also different from those of the designed scaffold, notably affecting the scaffold performance as applied subsequently to tissue engineering. This dissertation aims to perform a comprehensive study on the printability and mechanical behavior of hydrogel scaffolds fabricated by extrusion bioprinting. The specific objectives are (1) to investigate the influence of design-, bioink-, and printing-related factors on the printability of hydrogel scaffolds, (2) develop an indirect printing technique to improve the printability of low-concentration hydrogels, (3) develop a numerical model representative of the elastic modulus of hydrogel scaffolds by considering the influence of printability, and (4) investigate the effect of crosslinkers on the scaffold's mechanical properties through experimental and numerical approaches. While studies on printing scaffolds from hydrogel(s) have been conducted, limited knowledge has been documented on hydrogels' printability. Current studies often consider one aspect of studying hydrogel printability (for example, bioink properties solely). The first part of this dissertation studies the multiple dimensions of printability for hydrogel scaffolds, including identifying the influence of hydrogel composition and printing parameters/conditions. Specifically, by using the hydrogels synthesized from alginate, gelatin, and methylcellulose (MC), flow behavior and mechanical properties, as well as their influence on the printability of hydrogels, were investigated. Pore size, strand diameter, and other dimensions of the printed scaffolds were examined; then, pore/ strand/ angular/ printability and irregularity were studied to characterize the printability. The results revealed that the printability could be affected by many factors; among them, the most important are those related to the hydrogel composition and printing parameters. This chapter also presents a framework to evaluate alginate hydrogel printability systematically, which can be adopted and used in the studies of other hydrogels for bioprinting. Low-concentration hydrogels have favorable properties for many cell functions in tissue engineering, but they are considerably limited from a scaffold fabrication point of view due to poor 3D printability. The second part of this dissertation is developing an indirect printing method to fabricate scaffolds made from a low-concentration of hydrogels as the second objective. This chapter briefly presents an indirect bioprinting technique to biofabricate scaffolds with low (0.5%w/v) to moderate (3%w/v) concentrations of alginate hydrogel using gelatin as a sacrificial bioink. Indirect-fabricated scaffolds were evaluated using compression, swelling, degradation, biological (primary rat Schwann cells), and morphological assessments. Results indicated that 0.5% alginate scaffolds have steep swelling changes, while 3.0% alginate scaffolds had gradual changes. 0.5% alginate demonstrated better cell viability throughout the study than 3.0% counterparts, though. It was concluded that this indirect bioprinting approach could be extended to other types of hydrogels to improve the printability of low-concentration hydrogels along with the biological performance of cells and avoid high shear stress during direct 3D bioplotting causing cell damage. One issue involved in 3D bioplotting is achieving the scaffold structure with the desired mechanical properties. To overcome this issue, various numerical methods have been developed to predict scaffolds' mechanical properties, but they are limited by the imperfect representation of scaffolds as fabricated. The third part of this dissertation is developing a numerical model to predict the elastic modulus (one important index of mechanical properties) of scaffolds, considering the penetration or fusion of strands in one layer into the previous layer as the third objective. For this purpose, the finite element method was used for the model development, while medium-viscosity alginate was selected for scaffold fabrication by the 3D bioplotting technique. The elastic modulus of the bioplotted scaffolds was characterized using mechanical testing; the results were compared with those predicted from the developed model, demonstrating a strong congruity amongst them. Our results showed that the penetration, pore size, and the number of printed layers have significant effects on the elastic modulus of bioplotted scaffolds and suggest that the developed model can be used as a powerful tool to modulate the mechanical behavior of bioplotted scaffolds. For improvement, the fourth part of the dissertation (or the fourth objective) is improving the developed model by considering the crosslinker's effect on the modeling. The use of a cation solution (a crosslinker agent such as CaCl2) is important for regulating the mechanical properties, but this use has not been well documented in the literature. Here, the effect of varied crosslinking agent volume and crosslinking time on 3D extrusion-based alginate scaffolds' mechanical behavior were evaluated using both experimental and numerical methods. Compression tests were used to measure each scaffold's elastic modulus; then, a finite element model was developed, and a power model was used to predict scaffold mechanical behavior. Results showed that crosslinking time and crosslinker volume both play a decisive role in modulating 3D bioplotted scaffolds' mechanical properties. Because scaffolds' mechanical properties can affect cell response, this study's findings can be implemented to modulate the elastic modulus of scaffolds according to the intended application. In conclusion, this dissertation presents the development of methods/models to study/represent the printability and mechanical properties of hydrogel scaffolds by using extrusion bioprinting, along with meaningful experimental and model-simulation results. The developed methods/models/results would represent an advance in bioprinting scaffolds for tissue engineering

Contact characteristics of viscoelastic bonded layers

AbstractA viscoelastic layered contact model has successfully been developed and solved analytically. The single layered linear viscoelastic material is assumed to be perfectly bonded to a rigid substrate in contact with a rigid indenter without friction under a step load. Two cases are considered: (a) a compressible layered material with a typical Poisson's ratio of 0.4 and (b) an incompressible layer with a Poisson's ratio of 0.5. Two viscoelastic models: Maxwell and three element standard linear solid are investigated. This paper highlights the methodology employed and the results obtained under various conditions

Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications

Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue disorders in a clinical setting remains scarce. Albeit with several in vitro breakthroughs over the past decade, standard musculoskeletal treatments are still limited to palliative care or surgical interventions with limited long-term effects and biological functionality. To better understand this lack of translation, it is important to study connections between basic science challenges and developments with translational hurdles and evolving frameworks for this fully disruptive technology that is biofabrication. This review paper thus looks closely at the processing stage of biofabrication, specifically at the bioinks suitable for musculoskeletal tissue fabrication and their trends of usage. This includes underlying composite bioink strategies to address the shortfalls of sole biomaterials. We also review recent advances made to overcome long-standing challenges in the field of biofabrication, namely bioprinting of low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially graded biological and structural scaffolds to help biofabricate more clinically relevant constructs. We further explore the clinical application of biofabricated musculoskeletal structures, regulatory pathways, and challenges for clinical translation, while identifying the opportunities that currently lie closest to clinical translation. In this article, we consider the next era of biofabrication and the overarching challenges that need to be addressed to reach clinical relevance

Organisational interventions for improving wellbeing and reducing work-related stress in teachers [Review].

Background: The teaching profession is an occupation with a high prevalence of work-related stress. This may lead to sustained physical and mental health problems in teachers. It can also negatively affect the health, wellbeing and educational attainment of children, and impose a financial burden on the public budget in terms of teacher turnover and sickness absence. Most evaluated interventions for the wellbeing of teachers are directed at the individual level, and so do not tackle the causes of stress in the workplace. Organisational-level interventions are a potential avenue in this regard. Objectives: To evaluate the effectiveness of organisational interventions for improving wellbeing and reducing work-related stress in teachers. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, ASSIA, AEI, BEI, BiblioMap, DARE, DER, ERIC, IBSS, SSCI, Sociological Abstracts, a number of specialist occupational health databases, and a number of trial registers and grey literature sources from the inception of each database until January 2015. Selection criteria: Randomised controlled trials (RCTs), cluster-RCTs, and controlled before-and-after studies of organisational-level interventions for the wellbeing of teachers. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: Four studies met the inclusion criteria. They were three cluster-randomised controlled trials and one with a stepped-wedge design. Changing task characteristics One study with 961 teachers in eight schools compared a task-based organisational change intervention along with stress management training to no intervention. It found a small reduction at 12 months in 10 out of 14 of the subscales in the Occupational Stress Inventory, with a mean difference (MD) varying from -3.84 to 0.13, and a small increase in the Work Ability Index (MD 2.27; 95% confidence interval (CI) 1.64 to 2.90; 708 participants, low-quality evidence). Changing organisational characteristics@ Two studies compared teacher training combined with school-wide coaching support to no intervention. One study with 59 teachers in 43 schools found no significant effects on job-related anxiety (MD -0.25 95% CI -0.61 to 0.11, very low-quality evidence) or depression (MD -0.26 95% CI -0.57 to 0.05, very low-quality evidence) after 24 months. The other study with 77 teachers in 18 schools found no significant effects on the Maslach Burnout Inventory subscales (e.g. emotional exhaustion subscale: MD -0.05 95% CI -0.52 to 0.42, low-quality evidence) or the Teacher Perceived Emotional Ability subscales (e.g. regulating emotions subscale: MD 0.11 95% CI -0.11 to 0.33, low-quality evidence) after six months. Multi-component intervention: One study with 1102 teachers in 34 schools compared a multi-component intervention containing performance bonus, job promotion opportunities and mentoring support to a matched-comparison group consisting of 300 schools. It found moderately higher teacher retention rates (MD 11.50 95% CI 3.25 to 19.75 at 36 months follow-up, very low-quality evidence). However, the authors reported results only from one cohort out of four (eight schools), demonstrating a high risk of reporting bias. Authors’ conclusions: We found low-quality evidence that organisational interventions lead to improvements in teacher wellbeing and retention rates. We need further evaluation of the effects of organisational interventions for teacher wellbeing. These studies should follow a complex- interventions framework, use a cluster-rando

Exploiting ground effects for surface transport noise abatement

Growing demand on transportation, road and railway networks has increased the risk of annoyance from these sources and the need to optimise noise mitigation. The potential traffic noise reduction arising from use of acoustically-soft surfaces and artificial roughness (0.3 m high or less) is explored through laboratory experiments, outdoor measurements at short and medium ranges and predictions. Although the applicability of ground treatments depends on the space usable for the noise abatement and the receiver position, replacing acoustically hard ground by acoustically-soft ground without or with crops and introducing artificial roughness configurations could achieve noise reduction along surface transport corridors without breaking line of sight between source and receiver, thereby proving useful alternatives to noise barriers. A particularly successful roughness design has the form of a square lattice which is found to offer a similar insertion loss to regularly-spaced parallel wall arrays of the same height but twice the width. The lattice design has less dependence on azimuthal source-receiver angle than parallel wall configurations

A combined analytical-experimental investigation of friction in cylinder liner inserts under mixed and boundary regimes of lubrication

It is necessary to develop an analytical solution in order to combine predictions with measured tribological parameters and fundamentally understand the mechanism of lubrication in a typical region of engine cycle, using tribometric studies. This paper deals with the development of such a representative approach. An analytical, rather than a numerical approach is expounded, as it is shown to suffice for the purpose of precise time-efficient predictions, which conform well to the measurements. The effect of surface topography, material and operating conditions are ascertained for the representative case of top compression ring—cylinder liner contact at the top dead centre reversal in transition from the compression to power stroke. Stainless steel uncoated surface used as press fit cylinder liners for niche original equipment manufacturer applications are compared with those furnished with a Nickel-Silicon Carbide wear-resistant coating of choice in high performance motorsport

Multicomponent polysaccharide alginate-based bioinks

3D-Bioprinting has seen a rapid expansion in the last few years, with an increasing number of reported bioinks. Alginate is a natural biopolymer that forms hydrogels by ionic cross-linking with calcium ions. Due to its biocompatibility and ease of gelation, it is an ideal ingredient for bioinks. This review focuses on recent advances on bioink formulations based on the combination of alginate with other polysaccharides. In particular, the molecular weight of the alginate and its loading level has an impact on materials performance, as well as the loading of the divalent metal salt and its solubility, which affects the cross-linking of the gel. Alginate is often combined with other polysaccharides that can sigificantly modify the properties of the gel, and can optimise alginate for use in different biological applications. It is also possible to combine alginate with sacrificial polymers, which can temporarily reinforce the 3D printed construct, but then be removed at a later stage. Other additives can be formulated into the gels to enhance performance, including nanomaterials that tune rheological properties, peptides to encourage cell adhesion, or growth factors to direct stem cell differentiation. The ease of formulating multiple components into alginate gels gives them considerable potential for further development. In summary, this review will facilitate the identification of different alginate-polysaccharide bioink formulations and their optimal applications, and help inform the design of second generation bioinks, allowing this relatively simple gel system to achieve more sophisticated control over biological processes

Whose responsibility is adolescent's mental health in the UK? The perspectives of key stakeholders

The mental health of adolescents is a salient contemporary issue attracting the attention of policy makers in the UK and other countries. It is important that the roles and responsibilities of agencies are clearly established, particularly those positioned at the forefront of implementing change. Arguably, this will be more efective if those agencies are actively engaged in the development of relevant policy. An exploratory study was conducted with 10 focus groups including 54 adolescents, 8 mental health practitioners and 16 educational professionals. Thematic analysis revealed four themes: (1) mental health promotion and prevention is not perceived to be a primary role of a teacher; (2) teachers have limited skills to manage complex mental health difculties; (3) adolescents rely on teachers for mental health support and education about mental health; and (4) the responsibility of parents for their children’s mental health. The research endorses the perspective that teachers can support and begin to tackle mental well-being in adolescents. However, it also recognises that mental health difculties can be complex, requiring adequate funding and support beyond school. Without this support in place, teachers are vulnerable and can feel unsupported, lacking in skills and resources which in turn may present a threat to their own mental well-being

Burnout and Depression: Two Entities or One

Objectives: The purpose of this study was to examine the overlap in burnout and depression. Method: The sample comprised 1,386 schoolteachers (mean age = 43; mean years taught = 15; 77% women) from 18 different U.S. states. We assessed burnout, using the Shirom-Melamed Burnout Measure, and depression, using the depression module of the Patient Health Questionnaire. Results: Treated dimensionally, burnout and depressive symptoms were strongly correlated (.77; disattenuated correlation, .84). Burnout and depressive symptoms were similarly correlated with each of 3 stress-related factors, stressful life events, job adversity, and workplace support. In categorical analyses, 86% of the teachers identified as burned out met criteria for a provisional diagnosis of depression. Exploratory analyses revealed a link between burnout and anxiety. Conclusions: This study provides evidence that past research has underestimated burnout–depression overlap. The state of burnout is likely to be a form of depression. Given the magnitude of burnout–depression overlap, treatments for depression may help workers identified as burned out. Copyright 2015 Wiley Periodicals, Inc. J. Clin. Psychol. 72:22–37, 2016

Exercising 'soft closure' on lay health knowledge? Harnessing the declining power of the medical profession to improve online health information

This study aims to address the increasingly complex medical predicament of low quality online health information contributing to lay health knowledge and consequently to clinical outcomes. We situate the predicament within a social change paradigm of individualism, choice, diminishing medical power, and emergence of the legitimacy of lay health knowledge. We contend that the prominence of lay health knowledge has been facilitated by the internet, and is due to a surge in broadcasting of experiential knowledge coupled with increased access to and enactment of medical and non-medically sanctioned online information on health and illness. We draw on and further test the application of social closure theory to help conceive a potential solution to this enduring problem. We conduct a quality assessment of an indicative case study, Apicectomies, and test the application of our notion of soft closure on its findings, resulting in targeted, feasible and potentially beneficial solutions to increasing the medical quality of online health information. We further present the extant application of soft closure by Healthtalkonline.org, which collates a medically reliable set of experiential knowledge on a range of health issues. As such, we propose a constructive re-enactment of the traditional closure of the medical profession on medical knowledge