期刊
BIOMEDICAL MATERIALS
卷 16, 期 3, 页码 -出版社
IOP Publishing Ltd
DOI: 10.1088/1748-605X/abc28b
关键词
nitric oxide; bone marrow stem cells; hydrogels; diabetic wound healing; SNAP
资金
- Qatar National Research Fund (Qatar Foundation) [NPRP12S-0310-190276]
- Central Laboratories Unit (CLU), Qatar University, Qatar
The study introduced a NO-releasing hydrogel that enhanced the wound-healing potential of bone marrow mesenchymal stem cells in diabetic wounds by increasing cell viability and proliferation. The slow release of NO from the hydrogel promoted continuous cell-proliferating activity, resulting in faster tissue regeneration.
Impaired diabetic wounds are one of the major pathophysiological complications caused by persistent microbial infections, prolonged inflammation, and insufficient angiogenic responses. Here, we report the development of nitric-oxide (NO) -releasing S-nitroso-N-acetyl-penicillamine (SNAP) -loaded chitosan/polyvinyl-alcohol hydrogel and its efficacy in enhancing the wound-healing potential of bone marrow mesenchymal stem cells in diabetic wounds. NO-releasing hydrogels significantly increased the cell viability and cell proliferation of hydrogen-peroxide (H2O2) -pretreated bone marrow stem cells (BMSCs), demonstrating their cytoprotective activity, which was further confirmed by gene expression of many times as much B-cell lymphoma 2 (Bcl-2), stromal cell-derived factor-1alpha (SDF-1 alpha), proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF). Furthermore, the SNAP-loaded hydrogel showed continuous cell-proliferating activity for six days, due to the slow release of NO from the hydrogel. Wound-healing studies of rabbits with induced diabetes showed that the application of SNAP-preconditioned BMSCs and NO-releasing hydrogels significantly sped up the healing process, compared to the control group. The wound-healing potential of BMSCs plus NO-releasing hydrogel was further validated by improved collagen deposition and epithelial layer formation, as confirmed by histopathological examination, as well as upregulation of VEGF and SDF-1 alpha biomarkers, as evidenced by gene-expression analysis. These results demonstrated that the application of BMSCs with NO-releasing hydrogel can promote faster regeneration of damaged tissues. Therefore, BMSCs plus NO-releasing hydrogels can be very useful for the treatment of diabetic wounds.
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