{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:43:44Z","timestamp":1793418224895,"version":"4.5.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The impaired healing of diabetic wounds under hyperglycemic conditions presents a major challenge. While\n                      <jats:italic>Aloe vera<\/jats:italic>\n                      gel is known for wound healing, the potential of its peel is underexplored. This study aimed to develop a scalable production method for\n                      <jats:italic>Aloe vera<\/jats:italic>\n                      peel-derived extracellular vesicle mimetics (AVp-EVMs), screen an optimal hydrogel for their delivery, and evaluate their efficacy in diabetic wound healing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      AVp-EVMs were produced via high-pressure homogenization and ultracentrifugation. Their effects on keratinocyte (HaCaT) proliferation\/migration and anti-inflammatory activity in LPS-stimulated macrophages were assessed\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Two hydrogels (non-ionic Sangelose 60L and ionic Carbomer 940) were screened as carriers. Finally, AVp-EVMs and the optimal hydrogel formulation (HG-EVM) were evaluated in a diabetic mouse wound model by monitoring wound closure, histology, and immunohistochemistry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AVp-EVMs showed good biocompatibility, promoted keratinocyte proliferation and migration, and were effectively internalized. They suppressed LPS-induced inflammation in macrophages by inhibiting NF-\u03baB activation and downstream pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6). The Sangelose hydrogel preserved the AVp-EVMs structure better than the Carbomer hydrogel. In diabetic mice, both AVp-EVMs and HG-EVM dressing promoted wound healing by enhancing re-epithelialization, reducing inflammation, and improving collagen deposition and alignment. The HG-EVM group achieved the highest wound closure rate (97.2%), significantly outperforming free AVp-EVMs injection (94.9%;\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study establishes a production method for AVp-EVMs. The non-ionic Sangelose hydrogel is an effective delivery vehicle, and the HG-EVM formulation enhances diabetic wound healing more effectively than free AVp-EVMs alone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbioe.2026.1768930","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:53:37Z","timestamp":1774421617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hydroxypropyl methylcellulose stearoxy ether 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