This randomized, controlled, investigator-blinded study performed by an independent research organization evaluated the appearance of periorbital and perioral wrinkles following twice-daily application of a specific blend of matrikines and matrikine-like synthetic peptides for skin rejuvenation over a 6-month period. Fine lines and wrinkles of 133 women, aged 38 years to 65 years, were assessed by an independent expert evaluator using a 5-point visual analogue score. Subjects were divided into 3 groups and randomized to receive either the matrikine-based technology (MPC) or 1 of the 2 materials containing traditional growth factors. Test materials were well tolerated, and all 3 significantly reduced the appearance of periorbital and perioral wrinkles after 3 and 6 months. In the group receiving the matrikine-based technology, periorbital wrinkles improved (≥ 1 unit) in 28% of subjects after 1 month, in 65% after 3 months, and in 81% after 6 months. Perioral wrinkles improved (≥ 1 unit) in 39% of subjects after 1 month, in 41% after 3 months, and in 59% after 6 months. Improvements in skin firmness, tactile roughness, and pore appearance were also observed with each test material. Use of MPC was associated with significantly improved skin elasticity after 2 months (20%) and at 6 months (16%), whereas the comparator materials had no significant effects on elasticity. This study demonstrates that topical use of a specific blend of matrikines and matrikine-like peptides is suitable for skin rejuvenation. It also provides evidence that topical use of this novel technology provides comparable results to other technologies that use traditional growth factors for skin rejuvenation, with an additional potential benefit of improved skin elasticity.