SummaryBackgroundThe safety and wrinkle‐reducing effects of multipolydioxanone (PDO) scaffold have been confirmed in animal, and clinical tests for 3 months, but the 12‐month outcomes, are unknown.ObjectiveThe safety and efficacy of multi‐PDO scaffold were tested in animal models and in humans for 12 months.MethodsIn the animal study, a multi‐PDO scaffold was implanted into the panniculus carnosus of rat dorsal skin (n = 18) and into the subcutaneous layer of minipig dorsal skin (n = 2) followed by histological staining and analysis. In a human study, a multi‐PDO scaffold was implanted deep into the periosteal subcutaneous layer under the wrinkles on the upper lips and forehead, followed by evaluation of clinical changes using digital photography and PRIMOS.ResultsA multi‐PDO scaffold was not observed after 6 months in rats and minipigs. However, the newly formed tissues within the hollow body of the scaffolds were maintained for up to 12 months. The enhanced effect on the upper lips and forehead wrinkles lasted up to 12 months without any side effects.ConclusionA multi‐PDO scaffold represents a new tool to improve upper lips and forehead wrinkles.