In Vitro Bioactivity of a Recombinant Human Collagen Peptide in a Filler Biomimetic Skin Model

Background Recombinant human collagen peptides (rhCol peptides) have demonstrated considerable promise in various biomedical applications, including wound healing, dermatological treatments, aesthetic procedures, cosmetic formulations, and personal healthcare. Recently, their incorporation as a bioactive component in dermal filler products has gained significant attraction within the aesthetic and cosmetic fields. Aims To elucidate the beneficial bio‐efficacy of rhCol peptides as a dermal filler, underlying mechanisms from both the cell and tissue levels were explored. Methods The stimulatory effect of rhCol peptides on extracellular matrix (ECM) production was confirmed in 2D human fibroblast cultures at mRNA levels. Subsequently, its impact on skin rejuvenation was illustrated, utilizing a novel, in‐house developed 3D in vitro filler biomimetic skin model, tissue morphology, epidermal proliferation and differentiation, as well as dermal ECM deposition were investigated. Transcriptomic analysis further offered an in‐depth view of molecular pathways underlying the phenotypical change observed at cellular and tissue levels. Results In the 2D cell model, matrix remodeling–related genes such as Collagen type I and III, Elastin, Fibrillin 1, Hyaluronic acid synthases 1, 2, and 3 were significantly upregulated upon treatment with rhCol III peptides. Its direct binding to the dermal scaffold was confirmed within a novel filler biomimetic in vitro skin model, providing compelling evidence of their beneficial effects on both epidermal and dermal compartments, embodied in improved epidermis regeneration (Ki67, COL17A1) and dermis remodeling (FBN1 and glycosaminoglycans). Furthermore, transcriptomic analysis provided valuable insights into the potential mechanisms of downregulated inflammation, senescence and apoptosis; upregulated integrin binding; and extracellular matrix formation resulted from the binding of rhCol III peptides to the dermal scaffold. Conclusions These findings collectively support the pro‐ECM potential of such rhCol III peptides as a promising biomaterial for dermal filler, as well as potential cosmetic applications. Limited by the gap between in vitro mimetic model and real injection, further clinical trials should be taken to reconfirm the potential benefits.