IV.3. Bioreactors in tissue engineering.

IV.3. Bioreactors in tissue engineering

Osteoblast response to rest periods during bioreactor culture of collagen-glycosaminoglycan scaffolds.

Flow perfusion bioreactors have been shown to enhance fluid transport and improve cell viability throughout tissue-engineered bone constructs. Furthermore, osteoblasts have been shown to be stimulated by flow during bioreactor culture, although the optimum flow regime to promote an osteogenic response has yet to be found. One problem is that bone cells lose their ability to respond to stimulation; however, mechanosensitivity can be restored by introducing resting periods between bouts of loading. The aim of this study was to analyze the effect of rest-insertion on the response of osteoblasts seeded on collagen-glycosaminoglycan scaffolds in a flow perfusion bioreactor over culture periods up to 14 days. Short-term rests of 5, 10, or 15 s and long-term rests of 7 h were incorporated into stimulation patterns. Cell distribution was enhanced in all flow groups, whereas static culture controls exhibited encapsulation. Cyclooxygenase-2 expression and prostaglandin E(2) levels increased significantly because of bioreactor culture over static controls. Osteopontin expression was significantly higher for the rest-inserted groups than the static control group or steady-flow group. These results indicate that the insertion of resting periods during flow enhances cellular distribution and osteogenic responses on collagen-glycosaminoglycan constructs cultured in a flow perfusion bioreactor

Stimulation of osteoblasts using rest periods during bioreactor culture on collagen-glycosaminoglycan scaffolds.

Osteoblasts respond to mechanical signals which play a key role in the formation of bone however, after extended periods of stimulation they become desensitised. Mechanosensitivity has been shown to be restored by the introduction of resting periods between loadings. The aim of this study was to analyse the effect of rest periods on the response of osteoblast-like cells seeded on collagen-glycosaminoglycan (CG) scaffolds in a flow perfusion bioreactor up to 14 days. Short (10 s) and long (7 h) term rests were incorporated into stimulation patterns. Constructs cultured in the bioreactor had a more homogenous cell distribution albeit with lower cell numbers than the static group. Osteopontin expression was significantly higher on the rest-inserted group than on the steady flow and static control. These results indicate that the insertion of short term rests during flow improves cellular distribution and osteogenic responses on CG constructs cultured in a flow perfusion bioreactor

Composite scaffold development and bioreactor culture for bone tissue engineering

THESIS 9254Bone tissue engineering involves seeding bone cells onto a scaffold, culturing this construct so that mineralisation occurs (by using signalling mechanisms such as growth factors or bioreactors) and then implanting it into a defect site in the body. This is called the tissue engineering triad: combining cells, scaffold and signalling to engineer tissue in vitro. In this work, the focus was on two aspects of the triad: scaffold development and signalling using a bioreactor. The general aim in this work was to develop a tissue engineered construct with enhanced osteogenic capabilities due to its structural and material properties, populated by a homogeneous distribution of stimulated cells

COVID-19:: Changing experiences of teaching and learning in postgraduate nursing education

The COVID19 Pandemic has highlighted the contribution nurses make to global health and wellbeing. Much of this contribution is possible due to the high quality education nurses receive at both an undergraduate and postgraduate level. The COVID19 pandemic has resulted in challenges for both nurses undertaking postgraduate education along with those responsible for delivering that education. This paper highlights those challenges many of which are specific to nurses and their subsequent meaning. The response by nursing faculty in light of these challenges is also articulate

The role of platelet-derived ADP and ATP in promoting pancreatic cancer cell survival and gemcitabine resistance

Platelets have been demonstrated to be vital in cancer epithelial-mesenchymal transition (EMT), an important step in metastasis. Markers of EMT are associated with chemotherapy resistance. However, the association between the development of chemoresistance, EMT, and the contribution of platelets to the process, is still unclear. Here we report that platelets regulate the expression of (1) human equilibrative nucleoside transporter 1 (hENT1) and (2) cytidine deaminase (CDD), markers of gemcitabine resistance in pancreatic cancer. Human ENT1 (hENT1) is known to enable cellular uptake of gemcitabine while CDD deactivates gemcitabine. Knockdown experiments demonstrate that Slug, a mesenchymal transcriptional factor known to be upregulated during EMT, regulates the expression of hENT1 and CDD. Furthermore, we demonstrate that platelet-derived ADP and ATP regulate Slug and CDD expression in pancreatic cancer cells. Finally, we demonstrate that pancreatic cancer cells express the purinergic receptor P2Y 12 , an ADP receptor found mainly on platelets. Thus ticagrelor, a P2Y 12 inhibitor, was used to examine the potential therapeutic effect of an ADP receptor antagonist on cancer cells. Our data indicate that ticagrelor negated the survival signals initiated in cancer cells by platelet-derived ADP and ATP. In conclusion, our results demonstrate a novel role of platelets in modulating chemoresistance in pancreatic cancer. Moreover, we propose ADP/ATP receptors as additional potential drug targets for treatment of pancreatic cancer. © 2017 by the authors

The TEAM project: Insights from investigating and enhancing assessment in science and health practical sessions with digital technologies.

In Higher Education, science and health degree programmes involve significant practical elements.  In many cases, students spend as much time in practical or clinical skill sessions each week as they do in classroom based lectures.  These hands-on sessions engage students, develop both soft and technical skills, while allowing theory to be put into practice.  However, in many cases, the design, assessment and feedback aspects of practical sessions has not received the attention warranted, with traditional approaches often persisting. This paper discusses a nationally funded, multi-institution enhancement project focused on implementing and evaluating digital technologies to enhance assessment in science and health practical sessions.  Via an initial baseline analysis, four thematic areas were identified for pilot development: [1] Pre-practical videos combined with online/app quizzes, [2] Electronic lab notebooks, [3] Digital Feedback and [4] Rubrics.  In collaboration with student partner groups, employers and academic staff, the TEAM (Technology Enhanced Assessment Methods) project designed and implemented 42 pilots in practical sessions across the four partner colleges, engaging almost 1,600 students.  In this paper, the key lessons identified during the baseline analysis which informed the project, as well as those from the subsequent survey and focus group evaluation of participants’ pilot experiences, will be presented.  Overall, the implementation of TEAM has represented a major success across the partner colleges, providing a strong foundation for continuous, iterative improvements in this field.

Vosaroxin: a new valuable tool with the potential to replace anthracyclines in the treatment of AML?

Introduction: Despite significant advances in diagnosis and supportive care, the majority of patients diagnosed with acute myeloid leukemia (AML) ultimately die of their disease. Standard intensive induction treatment continues to comprise cytarabine and a topoisomerase II (topo II) poison, usually an anthracycline. Vosaroxin , a novel first-in-class quinolone derivative has been developed for use in the treatment of AML as a new-generation topo II inhibitor. It has shown promising activity as a monotherapy and also in combination with intermediate dose cytarabine (IDAC) in relapsed and refractory patient cohorts with minimal toxicity and good tolerability. Areas covered: The authors discuss the mechanism of action of vosaroxin, the pharmacokinetics, safety and tolerability, preclinical and clinical trial results available as well as areas of ongoing research. Expert opinion: Vosaroxin has shown efficacy as a novel cytotoxic agent, and despite a similar mechanism of action has significant advantages over anthracyclines. It evades common resistance pathways of p53 and P-glycoprotein (P- gp) and does not appear to generate significant reactive oxygen species (ROS) associated with these agents. Should future investigation confirm its efficacy and advantageous safety profile, vosaroxin could potentially replace older generation topoisomerase poisons in the treatment of AML and other malignant conditions