Accelerated scarless wound healing by dynamical regulation of angiogenesis and inflammation with immobilized asiaticoside and magnesium ions in silk nanofiber hydrogels.

It remains a challenge to effectively regulate the complicated microenvironment during the wound healing process. The optimization of synergistic action of angiogenesis and inflammation is considered critical for quicker scarless wound regeneration. Here, the silk nanofiber (SNF) acts as a multifunctional carrier to load hydrophobic asiaticoside (AC) and hydrophilic Mg²⁺, and also serves as an element to assemble injectable hydrogels, forming a bioactive matrix with improved angiogenic and anti-inflammatory capacities (SNF-AC-Mg). Mg²⁺ and AC distributed homogeneously inside the silk nanofiber hydrogels without compromising the mechanical performance. 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 effectively achieving the 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 SNFs in designing bioactive niches with complicated cues, which will favor the functional recovery of different tissues in the future.