Resumen

Objectives: To understand the immunologically different pathways that biostimulating fillers can take, in other words not all biostimulants are the same. Introduction: Initial macrophage response to biostimulatory substances is key in determining the subsequent behavior of fibroblasts and the organization of newly synthesized collagen. Histological studies suggest that calcium hydroxylapatite (CaHA) filler initiates a regenerative healing response with collagen and elastin deposition similar to natural, healthy tissue rather than an inflammatory response with fibrosis. The aim of the study is to characterize the in vitro macrophage response to two biostimulatory fillers, CaHA and PLLA, and evaluate their inflammatory potential. Materials / method: Primary human macrophages were incubated with 2 dilutions (1:50 and 1:100) of commercially available CaHA or PLLA. After 24 hours incubation, an inflammation array was used to screen for the expression of 40 cytokines by macrophages. ELISA was used to confirm array results. Results: Four cytokines were significantly upregulated in M1 macrophages incubated with PLLA compared to both unstimulated controls and CaHA: CCL1 (P<0.001), TNFRII (P<0.01), MIP-1α (P<0.05), and IL-8 (P<0.001). In M2 macrophages, MIP-1α (P<0.01) and MIP-1β (P<0.01) were significantly upregulated by PLLA compared to CaHA and unstimulated controls. Conclusion: Together, these findings indicate that the CaHA mode of action is a non-inflammatory response while PLLA initiates expression of several cytokines known to play a role in inflammation. Our study supports the concept that these two 'biostimulatory' fillers follow distinct pathways and should be considered individually with regard to mechanism of action.