Proliferative and secretory activity of human fibroblasts with different PLA fillers

Objectives: The aim of this study is to investigate cytotoxicity of polylactic acid fillers, proliferative and secretory function of human fibroblasts in vitro after adding different PLA fillers, such as PLLA/ PDLA. Introduction: The international interest to PLA fillers has recently become extremely high. There is plenty of different PLA fillers: PLLA or PDLA, some of them have high or low molecular weight, some of them look like broken glass, others have round shape. Besides, the size of particles vary a lot. Some PLA fillers have carboxymethylcellulose or mannitol. The biggest part of scientific works about mechanism of action was made on animal cells/ animals in vivo with the use of only one PLA filler. This approach can’t be called objective and leads to some gaps. Materials / method: An enantiomeric composition, molecular weight, size and shape of PLA particles of 4 different PLA fillers were investigated and compared to instruction’s parameters. Human fibroblasts of 4-7 passage were cultivated and divided into two series: experimental (+PLA filler) and control (+sterile water). Samples were tested in six replicates at 3 control times: 24, 48, and 72 h. To characterize proliferative activity, cytotoxicity - microscopy was used. To determine fibronectin and VEGF-A level enzyme-linked immunosorbent assay was used. Results: The determination of physical and chemical properties revealed lower molecular weights. All PLA fillers showed no cytotoxicity. The maximum doubling time was observed for the test culture in the presence of PLLA №1 (~49 h), exceeding the average doubling time of the test culture (~35 h). A statistically significant increase in VEGF-A was demonstrated when fibroblasts were exposed to PLLA №1. Culturing cells with the PDLA №4 and PLLA №1, showed more intensive accumulation of fibronectin. Conclusion: The differences identified (lower molecular weights) may be due to different methods for determining polymer molecular weight or to its natural degradation due to hydrolysis by atmospheric moisture. More intense accumulation of VEGF-A was observed during culture with PLLA №1, which means not only PDLA leads to VEGF-A production. More intense accumulation of fibronectin was observed during culture with PLLA №1 and PDLA №4, which means that both isomers D and L show the stimulating ability to induce fibronectin production.