Fig. 2

The synthesis methods of EVs combined with hydrogels for wound healing. The synthetic approaches for EV-loaded hydrogels can be categorized as follows: (1) Combining EVs after crosslink: sequential crosslinking followed by EV absorption; (2) Crosslink after combining EVs: pre-mixing EVs with hydrogel precursor and subsequent crosslinking; (3) Crosslink in situ through separation of raw materials: simultaneous injection of cross-linkable precursors mixed with EVs at the wound site for in-situ gelation; (4) Crosslink in situ through temperature control: injection of EVs mixed with thermosensitive hydrogel precursors, achieving in-situ gelation through temperature changes; (5) Crosslink in situ through shear thinning: pre-crosslinking of EVs with shear-thinning hydrogels, leading to hydrogel liquefaction through injection-induced shear forces to adapt to wound contours and subsequent in-situ gelation; (6) 3D bioprinting: formation of a bio-ink by combining EVs and hydrogel precursors, followed by 3D printing technology for composite hydrogel preparation