Абстракт

Objectives: More detailed understanding of the biological mechanism of action of poly-L-lactic acid in human skin. Introduction: Injectable poly-L-lactic acid is indicated for use in people with healthy immune systems for the correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles. In our present study, we first studied in detail the molecular effects of poly-L-lactic acid (PLLA) injections on human full-thickness 3D skin models comprising fibroblasts and keratinocytes. Materials / method: Using gene expression profiling, we detected a significant effect of PLLA on day 5 after injection not only on epidermal proliferation (highly significant effect on epidermal thickness), but also a stimulatory effect on integrins (ITGA5/ITGB3) and laminins (LAMB3/LAMC2), which were essential components of the dermal-epidermal junction responsible for skin integrity and resistance to external mechanical forces. Results: Interestingly, on day 14 and 28 after PLLA injection, immunohistochemical analyses exhibited a stimulated collagen I production in these models, whereas expression of collagen III was not affected, which correlates to previous clinical findings. These effects could be attributed at least in part to the upregulation of IL-1b and subsequently of CXCL6 which is capable to chemoattract neutrophils and to stimulate collagen I synthesis in fibroblasts as we could demonstrate using a pro-collagen type I peptide α1 ELISA. Conclusion: Taken together, our data provide for the first time molecular insights into the stimulatory effects of PLLA injections on collagen I production in novel human long-term 3D skin models comprising macrophages.