Mussel-Inspired Surface Immobilization of Heparin on Magnetic Nanoparticles for Enhanced Wound Repair via Sustained Release of a Growth Factor and M2 Macrophage Polarization

Abstract

Efficient reconstruction of a fully functional skin after wounds requires multiple functionalities of wound dressing due to the complexity of healing. In these regards, topical administration of functionalized nanoparticles capable of sustainably releasing bioactive agents to the wound site may significantly accelerate wound repair. Among the various nanoparticles, superparamagnetic iron oxide (Fe₃O₄) nanoparticles gain increasing attractiveness due to their intrinsic response to an external magnetic field (eMF). Herein, based on the Fe₃O₄ nanoparticle, we developed a fibroblast growth factor (bFGF)-loaded Fe₃O₄ nanoparticle using a simple mussel-inspired surface immobilization method. This nanoparticle, named as bFGF-HDC@Fe₃O₄, could stabilize bFGF in various conditions and exhibited sustained release of bFGF. In addition, an <i>in vitro</i> study discovered that bFGF-HDC@Fe₃O₄ could promote macrophage polarization toward an anti-inflammatory (pro-healing) M2 phenotype especially under eMF. Further, <i>in vivo</i> full-thickness wound animal models demonstrated that bFGF-HDC@Fe₃O₄ could significantly accelerate wound healing through M2 macrophage polarization and increased cell proliferation. Therefore, this approach of realizing sustained the release of the growth factor with magnetically macrophage regulating behavior through modification of Fe₃O₄ nanoparticles offers promising potential to tissue-regenerative applications.