To　design　a　scaffold　controlled　release　system　for　skin　tissue　engineering,　fish　collagen/chitosan/chondroitin　sulfate　scaffolds　were　fabricated　by　freeze-drying　and　incorporated　with　bEGF-loaded　PLGA　microspheres　(MPs).　SEM　showed　that　the　scaffolds　exhibited　an　interconnected　porous　structure,　and　the　spherical　MPs　were　uniformly　distributed　into　the　scaffolds.　The　higher　swelling　and　degradation　rate　of　scaffolds/MPs　could　lead　to　a　higher　diffusion　rate　of　MPs　from　the　scaffolds,　causing　an　increase　in　the　protein　release.　The　release　rate　of　proteins　could　be　adjusted　by　the　size　of　MPs　and　the　ratio　of　collagen　to　chitosan　of　scaffolds.　Circular　dichroism　spectroscopy　and　MU　of　bFGF　after　release　indicated　that　the　released　bFGF　retained　its　structural　integrity　and　bioactivity　during　preparation.　Cell　proliferation　and　in　vivo　evaluation　results　suggested　that　the　scaffolds/MPs　had　a　good　biocompatibility　and　an　ability　to　promote　fibroblast　cell　proliferation　and　skin　tissue　regeneration.　These　results　demonstrated　that　this　scaffold/MP　controlled　release　system　has　the　potential　for　skin　tissue　engineering.　(C)　2015　Elsevier　B.V.　All　rights　reserved.