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The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High\u2010purity functional mitochondria with an intact structure are extracted from human umbilical cord\u2010derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC\u2010derived mitochondria (hUCMSC\u2010Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC\u2010Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC\u2010Mito\u2010loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair.<\/jats:p>","DOI":"10.1002\/adhm.202302128","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T15:53:40Z","timestamp":1699026820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mesenchymal Stem Cell\u2010Derived Mitochondria Enhance Extracellular Matrix\u2010Derived Grafts for the Repair of Nerve Defect"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3451-2090","authenticated-orcid":false,"given":"Jun","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Neurosurgery General Hospital of Chinese People Liberty Army  No. 28 Fuxing Road Beijing 100853 P. R. 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