自愈水凝胶
伤口愈合
间充质干细胞
微泡
丝素
富血小板血浆
血管生成
血小板活化
蛋白酵素
化学
细胞生物学
材料科学
癌症研究
免疫学
血小板
医学
生物
生物化学
丝绸
酶
有机化学
复合材料
小RNA
基因
作者
Bianza Moïse Bakadia,Abeer Ahmed Qaed Ahmed,Lallepak Lamboni,Zhijun Shi,Biampata Mutu Mukole,Ruizhu Zheng,Mazono Pierre Mbang,Zhang Bi,Mario Gauthier,Guang Yang
标识
DOI:10.1016/j.bioactmat.2023.05.002
摘要
The management of diabetic wounds remains a critical therapeutic challenge. Platelet-rich plasma (PRP) gel, PRP-derived exosomes (PRP-Exos), and mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated therapeutic potential in wound treatment. Unfortunately, their poor mechanical properties, the short half-lives of growth factors (GFs), and the burst release of GFs and exosomes have limited their clinical applications. Furthermore, proteases in diabetic wounds degrade GFs, which hampers wound repair. Silk fibroin is an enzyme-immobilization biomaterial that could protect GFs from proteases. Herein, we developed novel dual-crosslinked hydrogels based on silk protein (SP) (sericin and fibroin), including [email protected], [email protected], and [email protected], to promote diabetic wound healing synergistically. [email protected] was prepared from PRP and SP using calcium gluconate/thrombin as agonist, while [email protected] and [email protected] were derived from exosomes and SP with genipin as crosslinker. SP provided improved mechanical properties and enabled the sustained release of GFs and exosomes, thereby overcoming the limitations of PRP and exosomes in wound healing. The dual-crosslinked hydrogels displayed shear-induced thinning, self-healing, and eradication of microbial biofilms in a bone-mimicking environment. In vivo, the dual-crosslinked hydrogels contributed to faster diabetic wound healing than PRP and SP by upregulating GFs expression, down-regulating matrix metalloproteinase-9 expression, and by promoting an anti-NETotic effect, angiogenesis, and re-epithelialization. Hence, these dual-crosslinked hydrogels have the potential to be translated into a new generation of diabetic wound dressings.
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