Accelerated Scarless Wound Healing by Dynamical Regulation of Angiogenesis and Inflammation with Immobilized Asiaticoside and Magnesium Ions in Silk Nanofiber Hydrogels

Abstract

It remains a challenge to regulate the complicated microenvironment effectively in the wound healing process. The optimization of synergistic action of angiogenesis and inflammation is considered critical for quicker scarless wound regeneration. Here, silk nanofiber (SNF) as a multifunctional carrier to load hydrophobic asiatisoside (AC) and hydrophilic Mg2+, and also as an element to assemble injectable hydrogel, forming a bioactive matrice with improved angiogenic and anti-inflammatory capacities (SNF-AC-Mg). Mg2+ and AC distributed homogeneously inside silk nanofiber hydrogels without the compromise of mechanical performances. Both Mg2+ and AC released slowly to continuously tune both angiogenic and inflammatory behaviors. The hydrogels exhibited good biocompatibility, inflammation inhibition, and pro-angiogenic properties in vitro, suggesting the synergistic bioactivity of AC and Mg2+. In vivo analysis revealed that the synergistic action of AC and Mg2+ resulted in better M2-type polarization of macrophages and angiogenesis during the inflammatory phase, while achieved effective inhibition of excessive accumulation of collagen and scar formation during the remodeling phases. The quicker scarless regeneration of the defects treated with SNF-AC-Mg implies the priority of SNF in designing bioactive niches with complicated cues, which will favor the functional recovery of different tissues in the future.