Abstract
The fabrication of highly biocompatible hydrogels with multiple unique healing abilities for the whole healing process, for example, multifunctional hydrogels with injectable, degradation, antibacterial, antihypoxic, and wound healing–promoting properties that match the dynamic healing process of skin flap regeneration, is currently a research challenge. Here, a multifunctional and dynamic coordinative polyethylene glycol (PEG) hydrogel with mangiferin liposomes (MF‐Lip@PEG) is developed for clinical applications through Ag–S coordination of four‐arm‐PEG‐SH and Ag+. Compared to MF‐PEG, MF‐Lip@PEG exhibits self‐healing properties, lower swelling percentages, and a longer endurance period. Moreover, the hydrogel exhibits excellent drug dispersibility and release characteristics for slow and persistent drug delivery. In vitro studies show that the hydrogel is biocompatible and nontoxic to cells, and exerts an outstanding neovascularization‐promoting effect. The MF‐Lip@PEG also exhibits a strong cytoprotective effect against hypoxia‐induced apoptosis through regulation of the Bax/Bcl‐2/caspase‐3 pathway. In a random skin flap animal model, the MF‐Lip@PEG is injectable and convenient to deliver into the skin flap, providing excellent anti‐inflammation, anti‐infection, and proneovascularization effects and significantly reducing the skin flap necrosis rate. In general, the MF‐Lip@PEG possesses outstanding multifunctionality for the dynamic healing process of skin flap regeneration.
Highlights
The fabrication of highly biocompatible hydrogels with multiple unique healing abilities for the whole healing process, for example, multifunctional hydrogels with injectable, degradation, antibacterial, antihypoxic, and wound healing–promoting properties that match the dynamic healing process of skin flap regeneration, is currently a research challenge
During the early stage of skin flap recovery, tissue suffers from damaged homeostasis and cell apoptosis caused by inflammation, ischemia, and hypoxia; in the proliferation period, the cells proliferate rapidly after endothelial cells exhibit adequate vascularization, while fibroblasts and mesenchymal stem cells help with healing and regeneration
We found that following treatment with mangiferin liposomes (MF-Lip)@polyethylene glycol (PEG) leaching liquor for 7 d, the expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in human endothelial vein cells (HUVECs) increased significantly in a dose-dependent manner at concentrations below 40 × 10−6 m (Figure 2b,c)
Summary
The fabrication of highly biocompatible hydrogels with multiple unique healing abilities for the whole healing process, for example, multifunctional hydrogels with injectable, degradation, antibacterial, antihypoxic, and wound healing–promoting properties that match the dynamic healing process of skin flap regeneration, is currently a research challenge. The promotion effect of MF-Lip60@PEG was dramatically decreased, similar to the results observed for MF’s effect on cell viability (Figures S8 and S9, Supporting Information). A lack of these factors can result in abnormal vessel formation.[31,32] In the present study, we found that following treatment with MF-Lip@PEG leaching liquor for 7 d, the expression levels of VEGF and bFGF in HUVECs increased significantly in a dose-dependent manner at concentrations below 40 × 10−6 m (Figure 2b,c).
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