RESUMEN
Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers. Recently, extracellular vesicles (EVs), naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins, lipids, and nucleic acids, have drawn wide attention due to their ability to promote wound healing and tissue regeneration. However, current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes. To circumvent these challenges, bioinspired cell-derived nanovesicles (CDNs) that mimic EVs were obtained by shearing mesenchymal stem cells (MSCs) through membranes with different pore sizes. Physical characterisations and high-throughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs. Moreover, these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway, resulting in enhancement of cell proliferation, cell migration, secretion of growth factors and extracellular matrix proteins, which all promoted tissue regeneration. Of note, MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEG-fibrin scaffold and animal model, accelerating wound healing in vitro and in vivo. These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.
RESUMEN
The technology of drug delivery systems (DDS) has expanded into many applications, such as for treating neurological disorders. Nanoparticle DDS offer a unique strategy for targeted transport and improved outcomes of therapeutics. Stroke is likely to benefit from the emergence of this technology though clinical breakthroughs are yet to manifest. This review explores the recent advances in this field and provides insight on the trends, prospects and challenges of translating this technology to clinical application. Carriers of diverse material compositions are presented, with special focus on the surface properties and emphasis on the similarities and inconsistencies among in vivo experimental paradigms. Research attention is scattered among various nanoparticle DDS and various routes of drug administration, which expresses the lack of consistency among studies. Analysis of current literature reveals lipid- and polymer-based DDS as forerunners of DDS for stroke; however, cell membrane-derived vesicles (CMVs) possess the competitive edge due to their innate biocompatibility and superior efficacy. Conversely, inorganic and carbon-based DDS offer different functionalities as well as varied capacity for loading but suffer mainly from poor safety and general lack of investigation in this area. This review supports the existing literature by systematizing presently available data and accounting for the differences in drugs of choice, carrier types, animal models, intervention strategies and outcome parameters.
