Photoacoustic Imaging of Angiogenesis Promoted by Microenvironment-Responsive Nitric Oxide-Releasing Hydrogel

Drug-loaded hydrogels with excellent adhesion, moisture, and biocompatibility are promising wound dressing and particularly appealing for chronic wound therapy due to their controllable and sustained drug release. However, the treatment effect of the hydrogel dressing is regularly assessed by ex vivo histology, hampering in vivo longitudinal monitoring of neovascularization for precise therapeutic efficiency evaluation. Herein, optical-resolution photoacoustic microscopy (OR-PAM) is adopted for longitudinal microvasculature imaging of the murine ear wound treated with a redox-responsive S-nitrosoglutathione-loaded guanosine-borate hydrogel. The hydrogel engineered via borate ester-mediated guanosine tetramerization features sustained nitric oxide release for more than 100 h. High-resolution OR-PAM images reveal vessel remodeling including initial vessel pruning, endothelial sprouting, and hierarchical branching over a two-week period. The treated wounds exhibit increased change rates of 63% in the vascular area density and 49% in the total vessel length compared with the control group, due to the high biocompatibility, resistance to the skin tensile strain, and sustained drug release of the hydrogel dressing. Integration of the responsive drug-releasing hydrogel dressing with the high-resolution OR-PAM for longitudinal feedback of the treatment outcome provides a promising theranostic platform to develop hydrogel dressing for chronic wound therapy such as diabetic ulcers.