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While traditional microsphere implants promote skin rejuvenation through collagen regeneration, their clinical utility is hampered by non\u2010biodegradability and risks such as granuloma formation. To overcome these limitations, this study employed microfluidic technology to develop highly uniform, novel injectable, highly bioactive, and degradable Astragalus polysaccharide\/silk fibroin (APS\/SF) composite microspheres for subcutaneous filling to promote collagen regeneration. We performed 3D simulations of droplet formation in a microfluidic chip using ANSYS Fluent to visualize the process. Experimental results indicated that these microspheres exhibited unprecedented uniformity (CV\u2009=\u20094.22%\u2009&lt;\u20095.00%) and circularity (0.90\u2009\u00b1\u20090.01), and degraded effectively in phosphate\u2010buffered saline solutions. Furthermore, the microspheres demonstrated excellent biocompatibility and blood compatibility. In\u00a0vitro experiments confirmed their ability to significantly promote the proliferation and migration of L929 fibroblasts. In\u00a0vivo animal studies further indicated that implanted microspheres effectively induced collagen regeneration. Collectively, this research highlighted the significant therapeutic potential of APS\/SF microspheres as an innovative and safe biomaterial for skin rejuvenation.<\/jats:p>","DOI":"10.1002\/jbm.a.70122","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:27:40Z","timestamp":1782919660000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Performance Evaluation of Highly Uniform Astragalus Polysaccharide\/Silk Fibroin Microspheres Fabricated via Microfluidics as Biodegradable Fillers: Collagen Regeneration and Tissue Reaction"],"prefix":"10.1002","volume":"114","author":[{"given":"Enshun","family":"Yang","sequence":"first","affiliation":[{"name":"Guizhou University of Traditional Chinese Medicine  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Die","family":"Xie","sequence":"additional","affiliation":[{"name":"Guizhou University of Traditional 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