Regulating　the　differentiation　of　implanted　stem　cells　into　neurons　is　crucial　for　stem　cell　therapy　of　traumatic　brain　injury　(TBI).　However,　due　to　the　migratory　nature　of　implanted　stem　cells,　precise　and　targeted　regulation　of　their　fate　remains　challenging.　Here,　neural　stem　cells　(NSCs)　are　bio-orthogonally　engineered　with　hyaluronic　acid　methacryloyl　(HAMA)　microsatellites　capable　of　sustained　release　of　differentiation　modulators　for　targeted　regulation　of　their　neuronal　differentiation　and　advanced　TBI　repair.　By　employing　bio-orthogonal　covalent　reactions　and　optimizing　the　microsatellite　size,　HAMA　microsatellites　can　stay　on　membranes　for　over　10　days　owing　to　the　minimal　detachment　or　endocytosis.　These　microsatellites　can　thus　migrate　together　with　engineered　NSCs　and　release　modulators　around　the　cells,　actively　inducing　45.1%　of　NSCs　to　differentiate　into　neurons　compared　to　only　18.8%　for　normal　NSCs.　These　microsatellite-engineered　stem　cells　improve　brain　tissue　repair　and　enhance　behavioral　recovery　in　TBI　rats　after　implantation.　This　strategy　holds　promise　for　the　advanced　treatment　of　TBI　and　other　neurodegenerative　diseases.