Paper Title
Studies on The Phenotypes of Macrophages Stimulated by Polylactic Acid Particles/Farnesol

Abstract
Wound healing is divided into four stages: foreign body invasion, inflammatory response, proliferation, and remodeling. Macrophages and fibroblasts play important roles in wound healing. Macrophages are involved in clearing pathogens, regulating inflammatory and immune responses, and thereafter tissue repair. Macrophages express M1 acute inflammatory phase and M2 tissue repair phase (anti-inflammatory phase) phenotypes during the wound healing process. Poly-L-lactic acid is a biocompatible and biodegradable synthetic polymer. Farnesol is a sesquiterpene that has antioxidant, anti-inflammatory, antibacterial and promoting collagen production effects. This study explored poly-L-lactic acid microparticles/farnesol as foreign mattersto stimulate macrophages to produce a polarization response by evaluating the changes in the M1 and M2 phases of macrophages. Hopefully,the phenotype changes would facilitatefibroblasts to produce collagen to help wound healing. Preliminary results showed that the IC50of farnesol was approximately 0.4 mM. LDH test showed that less than 2 mg/mL of poly-L-lactic acid microparticles didn’t cause macrophages death. Adding poly-L-lactic acid microparticlesto macrophages culture revealed that the inflammatory factors IL-6 and TNF-α in the M1 acute inflammatory phase gradually decreased over the days of culture (30% decrease as after day 5 culturing). Interestingly, adding 0.4 mM farnesol significantly reduced the expressions of IL-6 and TNF-α. On the contrary, on day-5 culturing, the anti-inflammatory factors IL-10 and TGF-β1 (M2 anti-inflammatory phase)significantly increased to about 20% as compared the levels of day-1 culturing.In summary, poly-L-lactic acid microparticles caused macrophages to produce a polarization reaction and expressed M1 acute inflammation and M2 anti-inflammatory phase (tissue repair phase). Importantly, farnesol helped to promote the expressions of IL-10 and TGF-β1 in M2 phase, indicating that farnesol has anti-inflammatory effects on cultured cells. Keywords - poly-L-lactic acid microparticles, farnesol, macrophages, polarization, M1 acute inflammatory phase, M2 anti-inflammatory phase