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Long-bone fractures have a high likelihood of nonunion, but the specific biological pathways involved in this severe consequence are unknown. Fractures often heal in an organized sequence, including the production of a hematoma and an early stage of inflammation, the development of a soft callus and hard callus, and eventually the stage of bone remodeling. Deficient healing can result in a persistent bone defect with instability, discomfort, and loss of function. In the treatment of nonunions, mesenchymal stem cells (MSCs) prove to be a promising and safe alternative to the standard therapeutic strategies. Moreover, novel scaffolds are being created in order to use a synergistic biomimetic technique to rapidly generate bone tissue. MSCs respond to acellular biomimetic matrices by regenerating bone. Extracellular vesicles (EVs) derived from MSCs have recently gained interest in the field of musculoskeletal regeneration. Although many of these techniques and technologies are still in the preclinical stage and have not yet been approved for use in humans, novel approaches to accelerate bone healing via MSCs and\/or MSC derivatives have the potential to reduce the physical, economic, and social burdens associated with nonhealing fractures and bone defects. In this review, we focus on providing an up-to-date summary of recent scientific studies dealing with the treatment of nonunion fractures in clinical and preclinical settings employing MSC-based therapeutic techniques.<\/jats:p>","DOI":"10.1177\/09636897231183530","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T07:28:32Z","timestamp":1689665312000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Stem Cells and Their Derivatives: An Implication for the Regeneration of Nonunion Fractures"],"prefix":"10.1177","volume":"32","author":[{"given":"Veronika","family":"Smolinska","sequence":"first","affiliation":[{"name":"Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia"},{"name":"National Institute of Rheumatic Diseases, Piestany, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Csobonyeiova","sequence":"additional","affiliation":[{"name":"National Institute of Rheumatic Diseases, Piestany, Slovakia"},{"name":"Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radoslav","family":"Zamborsky","sequence":"additional","affiliation":[{"name":"National Institute of Rheumatic Diseases, Piestany, Slovakia"},{"name":"Department of Orthopaedics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia"},{"name":"National Institute of Children\u2019s Diseases, Bratislava, Slovakia"},{"name":"Centre for Tissue Engineering and Regenerative Medicine\u2013Translational Research Unit, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5074-9621","authenticated-orcid":false,"given":"Lubos","family":"Danisovic","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia"},{"name":"National Institute of Rheumatic Diseases, Piestany, Slovakia"},{"name":"Centre for Tissue Engineering and Regenerative Medicine\u2013Translational Research Unit, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/17453674.2017.1321351."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-017-3734-5."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-1383(07)80005-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21443."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-011-1338-z."},{"issue":"4","key":"e_1_3_2_7_2","first-page":"287","article-title":"Fracture healing: the diamond concept Peter","volume":"144","author":"Giannoudis P","year":"2011","unstructured":"Giannoudis P, Eihorn T, Marsh D. 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