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Bone marrow mesenchymal stem cells are an ideal candidate for bone tissue engineering due to their osteogenic potential. Along with chemical, mechanical signals such as fluid shear stress have been found to influence their differentiation characteristics. But the range of fluid shear experienced in vivo is too wide and difficult to generate in a single device. We have designed a microfluidic device that could generate four orders of shear stresses on adherent cells. This was achieved using a unique hydraulic resistance combination and linear optimization to the lesser total length of the circuit, making the device compact and yet generating four logarithmically increasing shear stresses. Numerical simulation depicts that, at an inlet velocity of 160 μl/min, our device generated shear stresses from 1.03 Pa to 1.09 mPa. In this condition, we successfully cultured primary rat bone marrow mesenchymal stem cells (rBMSCs) in the device for a prolonged period of time in the incubator environment (four days). Higher cell proliferation rate was observed in the intermittent flow at 1.09 mPa. At 10 mPa, both upregulation of osteogenic genes and higher alkaline phosphatase activity were observed. These results suggest that the intermittent shear of the order of 10 mPa can competently enhance osteogenic differentiation of rBMSCs compared to static culture.

Myocardium Infarction (MI) is one of the foremost cardiovascular diseases (CVDs) causing death worldwide, and its case numbers are expected to continuously increase in the coming years. Pharmacological interventions have not been at the forefront in ameliorating MI-related morbidity and mortality. Stem cell-based tissue engineering approaches have been extensively explored for their regenerative potential in the infarcted myocardium. Recent studies on microfluidic devices employing stem cells under laboratory set-up have revealed meticulous events pertaining to the pathophysiology of MI occurring at the infarcted site. This discovery also underpins the appropriate conditions in the niche for differentiating stem cells into mature cardiomyocyte-like cells and leads to engineering of the scaffold via mimicking of native cardiac physiological conditions. However, the mode of stem cell-loaded engineered scaffolds delivered to the site of infarction is still a challenging mission, and yet to be translated to the clinical setting. In this review, we have elucidated the various strategies developed using a hydrogel-based system both as encapsulated stem cells and as biocompatible patches loaded with cells and applied at the site of infarction.

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Our logarithmic microfluidic device shows the dependence of cancer metastasis, recurrence and drug resistance on fluid shear stress mechanotransduction in cancer microenvironment and circulation.

There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients’ quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as “Safe and Effective” products. However, the underlying challenges involved in the development, scalability, and characterization of these injectable products are critical. Moreover, the guidelines available do not provide a clear understanding of these complex products, making it difficult to anticipate the regulatory requirements. Thus, it becomes imperative to comprehend the criticalities and develop an understanding of these products. This review discusses various complexities involved in the parenteral products such as complex drug substances, excipients, dosage forms, drug administration devices like pre-filled syringes and injector pens, and its different characterization tools and techniques. The review also provides a brief discussion on the regulatory aspects and associated hurdles with other parenteral products. Graphical abstract

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