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Diabetic bone defect repair is one of the major challenges in clinic, because the pathological microenvironments such as hyperglycemia, oxidative stress, and inflammation exist in the bone defect area of diabetes mellitus. Although the current tissue-engineered bone has achieved favorable bone regeneration and functional reconstruction, it is still unsatisfactory for diabetic bone defect repair only by correcting a single pathological factor. In this study, we develop a multifunctional nano-releasing system of GelMA/HAMA microgels-encapsulated Mg2+/Emodin (MgEm) nanorods based on MOF design principle (denoted as MEGH) for reversing the diabetic pathological microenvironment. For the slow-release system of MEGH microgels, Emodin exert the hypoglycemic, antioxidant, and anti-inflammatory function, while Mg2+ ions could promote angiogenesis for bone regeneration. Subsequently, we combine decalcified bone matrix with the bone regenerative units based on BMSCs-loaded MEGH microgels (BMSCs@MEGH-D) for the construction of tissue-engineered bone. Finally, the pre-constructed BMSCs@MEGH-D scaffolds successfully promote the vascularized bone regeneration in diabetic rabbit skull models due to the effective correction of diabetic pathological microenvironment. The underlying mechanism indicates a synergetic efficacy of regulate glucose, inflammation, oxygen-related bioprocesses, as well as osteogenesis-related pathways. Our findings provide a promising treatment for reversing the diabetic pathological microenvironment to accelerate bone defect repair.
Wang et al. (Wed,) studied this question.