The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, College of Materials and Textiles, Zhejiang Sci-Tech University, Hangzhou 310018, PR China.
The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, College of Materials and Textiles, Zhejiang Sci-Tech University, Hangzhou 310018, PR China.
Int J Biol Macromol. 2020 Jun 15;153:1058-1069. doi: 10.1016/j.ijbiomac.2019.10.236. Epub 2019 Nov 19.
The infected diabetic wound ulcer is a significant problem for the diabetic patients, which leads to removal of affected foot site due to its delayed/non-healing tissues. The poly-microbial infections and active matrix metalloproteinases (MMP) are the significant influencing factors to delayed healing in diabetic mice. The main purposes of present investigation are to evaluation the targeted inactivation of MMP and avoid polymicrobial infections by using a combined therapeutic effect of metal chelating dipeptide (L-carnosine) and curcumin with the biocompatible silk protein hydrogel (L-car@cur/SF) dressing in the infected diabetic wound ulcer. The in vitro biological assay methods, such as, cell viability, anti-oxidant activity, anti-inflammatory macrophage cells and inhibition collagenase exhibited that the designed hydrogel matrix to be human cell compatible and could be accelerate for significant diabetic healing potential. The activation of cur/SF matrix by the L-carnosine was persuading the inactivation of matrix metalloproteinase-9 (MMP-9) through its potent chelating effects of Zn ions from the MMP-9 active center. The L-car@cur/SF hydrogel was demonstrated for the effective MMP-9 inactivation and bacterial inhibition via in vivo mice wound site, which indorsed the diabetic wound healing efficiency in streptozotocin-tempted diabetic mice.
受感染的糖尿病溃疡是糖尿病患者的一个重大问题，由于其组织延迟/不愈合，导致受影响的脚部部位被切除。多微生物感染和活性基质金属蛋白酶 (MMP) 是糖尿病小鼠愈合延迟的重要影响因素。目前研究的主要目的是通过使用金属螯合二肽（L-肌肽）和姜黄素与生物相容的丝蛋白水凝胶（L-car@cur/SF）敷料的联合治疗效果，靶向失活 MMP 并避免多微生物感染，从而评估对受感染的糖尿病溃疡的治疗效果。体外生物测定方法，如细胞活力、抗氧化活性、抗炎巨噬细胞和胶原酶抑制活性表明，设计的水凝胶基质与人细胞相容，并能显著加速糖尿病的愈合潜力。L-肌肽对 cur/SF 基质的激活通过其对 MMP-9 活性中心锌离子的强烈螯合作用，促使基质金属蛋白酶-9（MMP-9）失活。L-car@cur/SF 水凝胶在体内小鼠伤口部位表现出有效的 MMP-9 失活和抑菌作用，这支持了链脲佐菌素诱导的糖尿病小鼠的糖尿病伤口愈合效率。
