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However, while systemic delivery (e.g., i.v. [intravenous]) may cause off\u2010target effects in different organs, the local administration has low efficiency due to fast clearance by body fluids. Herein, a delivery system for human ASCs secretome based on a hydrogel formed of star\u2010shaped poly(ethylene glycol) (starPEG) and the glycosaminoglycan heparin (Hep) that is suitable to continuously release pro\u2010regenerative signaling mediators such as interleukin (IL)\u20104, IL\u20106, brain\u2010derived neurotrophic factor, glial\u2010cell neurotrophic factor, and beta\u2010nerve growth factor over 10 days, is reported. The released secretome is shown to induce differentiation of human neural progenitor cells and neurite outgrowth in organotypic spinal cord slices. In a complete transection SCI rat model, the secretome\u2010loaded hydrogel significantly improves motor function by reducing the percentage of ameboid microglia and systemically elevates levels of anti\u2010inflammatory cytokines. Delivery of ASC\u2010derived secretome from starPEG\u2010Hep hydrogels may therefore offer unprecedented options for regenerative therapy of SCI.<\/jats:p>","DOI":"10.1002\/adhm.202202803","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T18:10:12Z","timestamp":1677262212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Sustained Release of Human Adipose Tissue Stem Cell Secretome from Star\u2010Shaped Poly(ethylene glycol) Glycosaminoglycan Hydrogels Promotes Motor Improvements after Complete Transection in Spinal Cord Injury Rat Model"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-4220","authenticated-orcid":false,"given":"Deolinda","family":"Silva","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine University of Minho  Campus de Gualtar Braga 4710\u2010057 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