Microfluidic-Based Droplets for Advanced Regenerative Medicine: Current Challenges and Future Trends

Abstract

Microfluidics is a promising approach for the facile and large-scale fabrication of monodispersed droplets for various applications in biomedicine. This technology has demonstrated great potential to address the limitations of regenerative medicine. Microfluidics provides safe, accurate, reliable, and cost-effective methods for encapsulating different stem cells, gametes, biomaterials, biomolecules, reagents, genes, and nanoparticles inside picoliter-sized droplets or droplet-derived microgels for different applications. Moreover, microenvironments made using such droplets can mimic niches of stem cells for cell therapy purposes, simulate native extracellular matrix (ECM) for tissue engineering applications, and remove challenges in cell encapsulation and three-dimensional (3D) culture methods. The fabrication of droplets using microfluidics also provides controllable microenvironments for manipulating gametes, fertilization, and embryo cultures for reproductive medicine. This review focuses on the relevant studies, and the latest progress in applying droplets in stem cell therapy, tissue engineering, reproductive biology, and gene therapy are separately evaluated. In the end, we discuss the challenges ahead in the field of microfluidics-based droplets for advanced regenerative medicine.

The Cultivation Modality and Barrier Maturity Modulate the Toxicity of Industrial Zinc Oxide and Titanium Dioxide Nanoparticles on Nasal, Buccal, Bronchial, and Alveolar Mucosa Cell-Derived Barrier Models

“…The combination of reliable mature barrier models [ 79 ] with fluid perfusion [ 80 , 81 ], as well as airborne particle uptake [ 47 , 48 ] within an air–liquid interface (i.e., using a nebulizer) will further approximate the models to simulate both chronic and acute nanomaterial exposure scenarios relevant for the human health [ 82 ]. We believe that further levels of investigation should elaborate more on the underlying molecular mechanisms of nanotoxicology involving DNA/RNA integrity [ 24 ], mitochondrial health [ 25 ] as well as apoptotic cell signaling [ 22 , 23 , 26 , 27 , 28 ].…”

“…By interfering with hepatocyte mitochondrial functions, cellular apoptosis, and extensive reactive oxygen species (ROS) release in mature tissue, nanoscale TiO 2 can cause severe developmental issues. Zinc oxide nanomaterials, on the other hand, show a more acute cytotoxic potential and thus higher risk capacity as demonstrated for in vitro studies on the lungs, nervous and digestive systems [ 21 , 22 , 23 ]. This higher cytotoxic potential can be attributed not only to cytotoxic mechanisms involving such metallic nanoparticles alone but also ion-shedding and the consequential accumulation of toxic free intracellular zinc ions triggering unfavorable events including genetic integrity [ 24 ], mitochondrial functionality, [ 25 ] as well as cell survival and apoptosis mechanisms including nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cell (NFκB) [ 26 , 27 ] and p53/p38 [ 22 , 23 , 28 ]).…”

Automated analysis of mitochondrial dimensions in mesenchymal stem cells: Current methods and future perspectives

“…Mitochondrial functions of individual MSCs can be evaluated in a more realistic, tissue-like setup [ [65] , [66] , [67] ]. A disbalance in the mitochondrial redox system during MSC cultivation for MSC-based therapeutic use has a major impact on treatment efficiency, as shown previously [ 68 ].…”

Gene knockdown in HaCaT cells by small interfering RNAs entrapped in grapefruit-derived extracellular vesicles using a microfluidic device

“…Advances in microfabrication technology have made it possible to produce various types of microfluidic devices (MDs). MDs are used in a wide range of applications, such as flow chemistry 32 , lab-on-chip 33,34 , analytical chemistry 35 , and medicine 36 . The devices are capable of handling small volumes of liquids and rapidly carrying out reactions.…”