ADSC-exo@MMP-PEG smart hydrogel promotes diabetic wound healing by optimizing cellular functions and relieving oxidative stress

Diabetic wound complications are financially costly and difficult to heal in worldwide. Whereas the therapies of diabetic wound, such as wound dressing, endocrine therapy or flap-transplantations, were not satisfied. Based on our previous study of exosome secreted by adipose-derived stem cell (ADSC-exo), we loaded ADSC-exo into the matrix metalloproteinase degradable polyethylene glycol (MMP-PEG) smart hydrogel. Physical and chemical properties of ADSC-exo@MMP-PEG smart hydrogel were tested by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), weight loss examination, etc. As the hydrogel degraded in response to MMP, ADSC-exo was released and subsequently enhanced cell function via Akt signaling. Moreover, treatment with ADSC-exo@MMP-PEG smart hydrogel significantly relieved the H₂O₂-induced oxidative stress, which was widely recognized as a major cause of diabetic wound nonhealing. Similar results were achieved in mice diabetic wound models, in which the ADSC-exo@MMP-PEG treatment group displayed a significantly accelerated wound healing. To summarize, the present smart hydrogel with enzyme-response and exosome-release was proved to be benefit for diabetic wounds healing, which provides a reliable theoretical basis for application of ADSC-exo in treatment of diabetic wounds.