4D-printed hydrogel with precise regulation of viability and environment of stem cells for diabetic skin wound healing

Diabetic wounds not only suffer from vascular and nerve damage, but also face the severe challenge of impaired stem cell activity. In recent years, although traditional tissue engineering strategies provide exogenous stem cells for the healing of diabetic wounds, they have not reversed the dilemma of stem cell proliferation and differentiation in a high-glucose environment. In this work, piRNA-hsa-32182 was first demonstrated to be highly expressed in diabetic wounds and significantly inhibit the differentiation and migration of adipose-derived mesenchymal stem cells (ADMSCs). Accordingly, a 4D-printed tissue engineering hydrogel and piRNA-hsa-32182 antagomir were prepared to precisely modulate the survival microenvironment of ADMSCs and accelerate diabetic wound healing. 4D printed tissue engineering hydrogels provided a highly ordered microenvironment for ADMSCs through internal space homogenization, thereby effectively improving the loading rate and survival rate of stem cells. In addition, piRNA-hsa-32182 antagomir effectively enhanced the migration of ADMSCs, thereby increasing the deposition and maturation of collagen on the wound and promoting angiogenesis. In summary, this study significantly improved the microenvironment of wounds through the synergy of bio-intelligent printing technology and gene expression regulation, providing a new clinical paradigm for the treatment of diabetic wounds.