Facilitating Wound Healing by Inducing M۲ Macrophage Polarization Using Polymeric Nanoparticles; an Experimental and Molecular Study

Introduction: Targeting macrophages has garnered significant research interest due to their pivotal role in inflammation, cancer, and wound healing. This study investigates the impact of nanoparticle design on macrophage interactions and its subsequent influence on wound healing. Materials and Methods: Four nanoparticles (hyaluronic acid, chitosan, dextran, and methacrylic acid) were selected based on their biocompatibility and targeting potential. Molecular dynamics simulations revealed that hyaluronic acid exhibited the most favorable interactions with the macrophage membrane, positioning it as a promising candidate. To validate these findings, an in vivo experiment was conducted using hyaluronic acid nanoparticles on wounded rabbits. Results: The results showed that the factors involved in the stability of hyaluronic acid nanoparticles, including contact area average (۴۰ nm۲), Gyration Radius analysis (۴.۵ nm) and time dependent Rg (۵.۸ nm) were at their lowest level compared to another nanoparticle. Also the lowest entropy (۷۰۰ kj/mol.k), minimum distance(۱.۱ nm) and energy average(-۲۰۰۰ kj/mol) showed the appropriate stability of hyaluronic acid nanoparticles. The results demonstrated that topical administration of hyaluronic acid nanoparticles significantly accelerated wound healing. The formulation had an average hydrodynamic diameter of approximately ۱۰۴ ± ۲۵ nm, a zeta potential of –۱۸ ± ۲ mV, and a polydispersity index (PDI) of ۰.۳۰۶. HA nanoparticles significantly reduced wound size compared to the control group on days ۷, ۱۴, and ۲۱ (p < ۰.۰۱). Conclusions: This study utilized molecular dynamics simulations (MDS) to explore the interaction between four nanoparticles (hyaluronic acid, chitosan, dextran, and methacrylic acid) and the macrophage membrane, focusing on their potential to stimulate macrophages and influence wound healing.

کلیدواژه ها:

Nanomaterials ، wound healing ، Human macrophages ، polarization ، Hyaluronic acid