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  • Among all possible mechanical stimuli applied to cells Fig E

    2019-07-06

    Among all possible mechanical stimuli applied to 1196800-39-1 (Fig. 1E), the most reliable ones are hydrostatic pressure, direct compression and application of fluid shear stresses. In the case of cartilage TE, the application of physical patterns can stimulate the synthesis of type II Collagen and glycosaminoglycans (GAGs), and promote chondrogenesis [33].
    Future perspectives Thanks to all the previous investigations done in the field of cartilage TE, it is not uncommon to find many diagnostic or analytical devices used in the clinic to clarify the biomechanics of the whole musculoskeletal system before applying any treatment or just for avoiding possible lesions. Namely, Auckland Bioengineering Institute (2014) developed an open software platform to cover all mechanisms behind the biomechanical behavior of the human body [98]. Furthermore, in the future it would be interesting to modulate the biogenesis of neocartilage from the biomechanical point of view not only to control the tissue development but also to tailor it for any application. The possibility to reproduce these biomechanical patterns in an ex vivo model for cartilage TE is also an interesting target. The use of bioreactors as a medical tool for tissue formation is highly recommended, not only for studying the cartilage development but also as therapeutic devices to develop advanced therapy medical products (ATMPs) for OA treatment (Fig. 4), for reducing inflammation and promoting ECM synthesis in the implanted area [99].
    Conclusions The following is the supplementary data related to this article.
    Transparency document
    Introduction With advances in science and technology for treatment of cancer, the number of cancer survivors continues to increase. There were more than 15.5 million cancer survivors at the end of 2015, and this number could rise to 20 million in the next 10 years [1]. However, a significant consequence of cancer chemotherapy often occurs that affects the quality of life of cancer survivors. Cognitive dysfunction may happen acutely or after a period following chemotherapy. The phenomenon, called chemotherapy-induced cognitive impairments (CICI), “chemobrain” or “chemofog”, can be subtle or severe. CICI can retard recovery to normal life for cancer survivors, and this condition involves loss of memory and learning ability, less attention and concentration, decreased executive function, and slower processing speed [[2], [3], [4], [5]]. A cancer with a substantial percentage of survivors is breast cancer [5]. However, 35%–70% of breast cancer survivors reported cognitive impairment after or even during the treatment [6]. Cognitive impairment affects one third of childhood cancer survivors [7]. In a national cross-sectional study, participants who had a cancer history reported memory impairment 40% more than those without cancer [8]. In a recent study, 65% of breast cancer patients experienced acute cognitive impairment and 61% of them had late cognitive decline, compared to 21% of patients had cognitive dysfunction before chemotherapy [9]. CICI can even last 20 years post-chemotherapy for breast cancer [10]. Breast cancer survivors who were treated with cyclophosphamide, methotrexate and fluorouracil about 21 years ago were recruited. Compared to a non-cancer group, the 196 cancer survivors self-reported more memory complains and poorer performance in neuropsychological examinations including verbal memory, processing speed, executive function and psychomotor speed [10]. However, there are also studies showing no significant cognitive changes before and after chemotherapy [[11], [12], [13]]. The central nervous system (CNS) is affected by chemotherapeutic agents, many of which do not cross the blood-brain barrier (BBB) [14]. Chemotherapy could lead to pathological changes such as reduced brain connectivity [[15], [16], [17], [18]]. Consistent with this notion, brain structure and function both are altered in CICI. Volume and density changes of white matter and grey matter of patients who had chemotherapy were determined by MRI [[19], [20], [21], [22]]. Altered prefrontal cortex and hippocampus also are associated with CICI [[23], [24], [25], [26], [27]]. Hippocampus is an area important for learning and memory in brain. Chemotherapy disrupted structure and function of hippocampus and impaired its neurogenesis, leading to cognitive deficits [28].