Nanotechnology is revolutionizing many sectors of science, from food preservation to healthcare to energy applications. Since 1995, when the first nanomedicines started being commercialized, drug developers have relied on nanotechnology to improve the pharmacokinetic properties of bioactive molecules. The development of advanced nanomaterials has greatly enhanced drug discovery through improved pharmacotherapeutic effects and reduction of toxicity and side effects. Therefore, highly toxic treatments such as cancer chemotherapy, have benefited from nanotechnology. Considering the toxicity of the few therapeutic options to treat neglected tropical diseases, such as leishmaniasis and Chagas disease, nanotechnology has also been explored as a potential innovation to treat these diseases. However, despite the significant research progress over the years, the benefits of nanotechnology for both diseases are still limited to preliminary animal studies, raising the question about the clinical utility of nanomedicines in this field. From this perspective, this review aims to discuss recent nanotechnological developments, the advantages of nanoformulations over current leishmanicidal and trypanocidal drugs, limitations of nano-based drugs, and research gaps that still must be filled to make these novel drug delivery systems a reality for leishmaniasis and Chagas disease treatment.
Gradients in mechanical properties, physical architecture and biochemical composition exist in a variety of complex tissues, yet 3D in vitro models that enable investigation of these cues on cellular processes, especially those contributing to vascularization of engineered tissues are limited. Here, a photopolymerization approach to create cell‐laden hydrogel biomaterials with decoupled and combined gradients in modulus, immobilized cell adhesive peptide (RGD) concentration, and proteolytic degradation enabling spatial encapsulation of vascular spheroids is reported to elucidate their impact on vascular sprouting in 3D culture. Vascular spheroids encapsulated in these gradient scaffolds exhibit spatial variations in total sprout length. Scaffolds presenting an immobilized RGD gradient promote biased vascular sprouting toward increasing RGD concentration. Importantly, biased sprouting is found to be dependent on immobilized RGD gradient characteristics, including magnitude and slope, with increases in these factors contributing to significant enhancements in biased sprouting responses. Conversely, reduction in biased sprouting responses is observed in combined gradient scaffolds possessing opposing gradients in RGD and modulus. The presented work is the first to demonstrate the use of a cell‐laden biomaterial platform to systematically investigate the role of multiple scaffold gradients as well as gradient slope, magnitude and orientation on vascular sprouting responses in 3D culture.
In articule number 2001706 by Georgia Papavasiliou and co‐workers, vascular cell‐laden gradient PEG hydrogels with five types of gradient combinations including immobilized cell adhesion peptide concentration (RGD), stiffness, and protease‐sensitivity are designed to investigate their role on spatial variations in vascular sprouting responses in 3D culture.
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