BACKGROUND AND PURPOSE: New capillaries are essential for deep tissue pressure injury wound healing. Tazarotene is a recently discovered small molecule drug and functions to promote neovascularization and tissue repair. At present, the application of tazarotene in the repair of pressure injuries has not previously been investigated. This study used poly (lactic-co-glycolic acid) (PLGA) as nanoparticle carriers loaded with tazarotene (Ta/PLGA NPs) for drug delivery and to overcome shortcomings associated with the low water solubility, short half-life, easy photolysis and low bioavailability of tazarotene itself. METHODS: The physicochemical properties, drug release and bioactivity of Ta/PLGA NPs were examined in vitro by transmission electron microscope, spectrophotometry and cell assays. Mouse models of deep tissue pressure injuries (DTPI) were established and the therapeutic effects and mechanisms of Ta/PLGA NPs in local wound repair were studied. RESULTS: The results showed that Ta/PLGA NPs were of uniform size and distribution and were non-toxic both in vitro and in vivo. In vivo experiments suggested that Ta/PLGA NPs significantly promoted DTPI wound repair through activation of the VEGF/VEGFR-Notch1/DLL4 signaling pathway. CONCLUSION: This study highlights the potential clinical significance of implementation of tazarotene small molecule drugs in combination with effective biomaterial carriers for the treatment of chronic refractory wounds, such as DTPI.