Engineered collagen/PLLA composite fillers to induce rapid and long-term collagen regeneration

Injectable subcutaneous fillers are used in medical aesthetics primarily to correct skin wrinkles. The limitations of collagen fillers include rapid degradation, lack of collagen regeneration effects and high-frequency injections. The regenerative filler of Sculptra (Aesthetic) offers prolonged regenerative effects; however, the slow collagen regeneration results in prolonged waiting time for the filling effects. Herein, we report a facile strategy to fabricate dermal fillers with rapid collagen regeneration. Crosslinked collagen was swollen in a weak acidic solution and coated onto the surface of poly(L-lactic acid) (PLLA) microspheres. The collagen@PLLA composite microspheres (Col@PLLA) were dispersed in an aqueous solution of sodium carboxymethyl cellulose (CMC) to form a porous sponge after lyophilization. <i>In vitro</i> studies verified the good safety and fibroblast affinity of the Col@PLLA fillers. The fillers were subcutaneously injected to evaluate the effects of collagen regeneration <i>in vivo</i>. Compared to the single collagen and PLLA microspheres, the Col@PLLA composite fillers showed significant collagen regeneration after injecting for 5 days. The regenerated type III and type I collagens of Col@PLLA maintained high levels after 4 months post-implantation. The inflammation response further validated the regenerative mechanism and long-lasting potential of this product. The Col@PLLA fillers achieved a significant enhancement in collagen regeneration.