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

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