Injectable facial fillers such as Sculptra stimulate collagen regeneration to fill wrinkles; however, the collagen regeneration is not satisfactory due to the slow emergence of filling effect. In this study, we designed a regenerative dermal filler to provide both immediate and long-lasting filling effects. A hydrogel matrix composed of crosslinked hyaluronic acid (HA) and collagen was engineered to encapsulate porous poly(L-lactide) (PLLA) microspheres and tranexamic acid (TXA). The hydrogel matrix was administered via intradermal injection to achieve wrinkle filling. TXA is released to exert skin-whitening effects, while the porous PLLA microspheres and their degradation product, lactic acid, continuously stimulate collagen regeneration over an extended period. Facial volume increased immediately following hydrogel injection. Large amounts of new Type I and Type III collagen are generated. The porous structure of PLLA microspheres facilitated the 'penetrating growth' of collagen fibers, which effectively filled facial depressions and smoothed wrinkles. Overall, the HA/collagen composite hydrogel filler exhibited excellent esthetic effects.