Nanosilk Increases the Strength of Diabetic Skin and Delivers CNP-miR146a to Improve Wound Healing.
Nanosilk Increases the Strength of Diabetic Skin and Delivers CNP-miR146a to Improve Wound Healing.
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DOI：
10.3389/fimmu.2020.590285
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发表时间：
2020
影响因子：
7.3
通讯作者：
Zgheib C
中科院分区：
文献类型：
--
作者：
Niemiec SM;Louiselle AE;Hilton SA;Dewberry LC;Zhang L;Azeltine M;Xu J;Singh S;Sakthivel TS;Seal S;Liechty KW;Zgheib C
糖尿病是一种代谢紊乱，与持续的促炎反应导致的慢性伤口的性质和风险增加有关。我们先前已经将自由基清除氧化铈纳米颗粒（CNP）缀合至抗炎microRNA（miR）-146a（称为CNP-miR 146 a），通过协同降低氧化应激和炎症来改善糖尿病伤口愈合，并且我们试图在局部应用中评估这种治疗。丝素蛋白是一种生物相容性聚合物，可以制成纳米结构，称为纳米丝。纳米丝的特征在于高强度密度比和表现出应变硬化的能力。因此，我们假设纳米丝将增强糖尿病皮肤的生物力学性质，并且纳米丝溶液可以有效地递送CNP-miR 146 a以改善糖尿病伤口愈合。通过伤口闭合率和炎症基因表达以及组织学分析来评估纳米丝将CNP-miR 146 a递送至小鼠糖尿病伤口并改善愈合的能力。纳米丝对人糖尿病皮肤的性质的影响通过测试局部应用7%纳米丝溶液后的生物力学性质来评估。用局部纳米丝和CNP-miR 146 a治疗的糖尿病鼠伤口在第14.5天愈合，相比之下，对照组中的第16.8天愈合（p = 0.0321）。用CNP-miR 146 a处理的伤口具有比对照更高的胶原蛋白水平（p = 0.0126），具有更高的TGFβ-1（p = 0.0092）、Col 3 α1（p = 0.0369）和Col 1 α2（p = 0.0454）的促纤维化基因表达。用CNP-miR 146 a治疗降低了IL-6（p = 0.0488）和IL-8（p = 0.0009）的促炎基因表达。用7%纳米丝溶液处理人糖尿病皮肤导致最大负荷和模量的显著改善（p < 0.05）。纳米丝溶液能够增强糖尿病皮肤的生物力学性能，并可以成功地递送CNP-miR 146 a，通过抑制促炎基因信号传导和促进促纤维化过程来改善糖尿病伤口愈合。
Diabetes mellitus is a metabolic disorder associated with properties and an increased risk of chronic wounds due to sustained pro-inflammatory response. We have previously of radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA (miR)-146a, termed CNP-miR146a, improves diabetic wound healing by synergistically lowering oxidative stress and inflammation, and we sought to evaluate this treatment in a topical application. Silk fibroin is a biocompatible polymer that can be fabricated into nanostructures, termed nanosilk. Nanosilk is characterized by a high strength-to-density ratio and an ability to exhibit strain hardening. We therefore hypothesized that nanosilk would strengthen the biomechanical properties of diabetic skin and that nanosilk solution could effectively deliver CNP-miR146a to improve diabetic wound healing. The ability of nanosilk to deliver CNP-miR146a to murine diabetic wounds and improve healing was assessed by the rate of wound closure and inflammatory gene expression, as well as histologic analysis. The effect of nanosilk on the properties of human diabetic skin was evaluated by testing the biomechanical properties following topical application of a 7% nanosilk solution. Diabetic murine wounds treated with topical nanosilk and CNP-miR146a healed by day 14.5 compared to day 16.8 in controls (p = 0.0321). Wounds treated with CNP-miR146a had higher collagen levels than controls (p = 0.0126) with higher pro-fibrotic gene expression of TGFβ-1 (p = 0.0092), Col3α1 (p = 0.0369), and Col1α2 (p = 0.0454). Treatment with CNP-miR146a lowered pro-inflammatory gene expression of IL-6 (p = 0.0488) and IL-8 (p = 0.0009). Treatment of human diabetic skin with 7% nanosilk solution resulted in significant improvement in maximum load and modulus (p < 0.05). Nanosilk solution is able to strengthen the biomechanical properties of diabetic skin and can successfully deliver CNP-miR146a to improve diabetic wound healing through inhibition of pro-inflammatory gene signaling and promotion of pro-fibrotic processes.
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影响因子：
14
作者：
Das S;Singh S;Dowding JM;Oommen S;Kumar A;Sayle TX;Saraf S;Patra CR;Vlahakis NE;Sayle DC;Self WT;Seal S
通讯作者：
Seal S
DOI：
10.1016/s0140-6736(15)60401-9
发表时间：
2015-02-01
期刊：
The lancet. Diabetes & endocrinology
影响因子：
--
作者：
Shah, Anoop Dinesh;Langenberg, Claudia;Hemingway, Harry
通讯作者：
Hemingway, Harry
影响因子：
4.6
作者：
Hehenberger, K;Kratz, G;Brismar, K
通讯作者：
Brismar, K
影响因子：
14
作者：
Min, BM;Lee, G;Park, WH
通讯作者：
Park, WH
影响因子：
4.9
作者：
Dowding, Janet M.;Dosani, Talib;Self, William T.
通讯作者：
Self, William T.