首页|45S5 Bioglass? works synergistically with siRNA to downregulate the expression of matrix metalloproteinase-9 in diabetic wounds
45S5 Bioglass? works synergistically with siRNA to downregulate the expression of matrix metalloproteinase-9 in diabetic wounds
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NSTL
Elsevier
? 2022Diabetic chronic wounds are difficult to heal because of the presence of excessive inflammation and high overexpression of matrix metalloproteinase-9 (MMP-9), which greatly affects the quality of life of patients with diabetes and increases the risk of death. Thus, the regulation of excessive inflammation and inhibition of MMP-9 overexpression are effective strategies to improve diabetic wound healing. The present study is the first to demonstrate that ion products of 45S5 Bioglass? (BG) can work with small interfering RNA of MMP9 (MMP9-siRNA) to reduce MMP-9 expression in tissue-forming cells and enhance the synthesis of extracellular matrix proteins (ECMs). Specifically, the BG ionic products can stimulate macrophages to convert to M2 phenotype, thereby creating a proregenerative inflammation microenvironment to indirectly suppress the expression of MMP-9 in tissue-forming cells. Chitosan nanoparticles encapsulating MMP9-siRNA (MMP9-siNP) can directly lower MMP-9 expression in tissue-forming cells. In addition, BG ionic products can promote the vascularization of endothelial cells and ECM protein synthesis by fibroblasts. Thus, injectable BG/sodium alginate (BG/SA) hydrogels loaded with MMP9-siNP can significantly accelerate the healing process of full-thickness excision wounds of diabetic rats by decreasing MMP-9 expression, improving collagen synthesis, and enhancing angiogenesis in the wounds, thereby demonstrating their great application potential in treating diabetic chronic wounds. Statement of significance: Excessive inflammation and high overexpression of MMP-9 have been considered as factors that severely hinder the healing process of diabetic chronic wounds. Effective strategies are required for the regulation of excessive inflammation and inhibition of MMP-9 overexpression to enhance diabetic wound healing. In the present work, an injectable bioglass/sodium alginate (BG/SA) hydrogel loaded with MMP9-siNP was developed; this hydrogel significantly accelerated the healing process of full-thickness excision wounds of diabetic rats by decreasing MMP-9 expression, improving collagen accumulation, and enhancing angiogenesis in the wounds. Thus, the BG/SA hydrogel loaded with MMP9-siNP has great potential for use in healing of diabetic chronic wounds.
NSTL
Elsevier
