Improvement of the wound healing properties of hydrogels with N-acetylcysteine through their modification with methacrylate-containing polymers,Biomaterials Science

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Improvement of the wound healing properties of hydrogels with N-acetylcysteine through their modification with methacrylate-containing polymers
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-11-07 , DOI: 10.1039/d0bm01479f
Lesly S. Gomez-Aparicio _{1,

2,

3,

4} , Johanna Bernáldez-Sarabia _{1,

2,

3,

4} , Tanya A. Camacho-Villegas _{4,

5,

6,

7,

8} , Pavel H. Lugo-Fabres _{4,

5,

6,

7,

8} , Néstor Emmanuel Díaz-Martínez _{4,

5,

6,

7} , Eduardo Padilla-Camberos _{4,

5,

6,

7} , Alexei Licea-Navarro _{1,

2,

3,

4} , Ana B. Castro-Ceseña _{1,

2,

3,

4,

9}

Affiliation

Hydrogels with antioxidant activity have shown to significantly improve the standard of care, because they promote efficient wound healing, i.e. regeneration. N-Acetylcysteine (NAC) is an antioxidant amino acid derivative that promotes complete tissue restoration. However, NAC has anticoagulant properties that may also hinder blood coagulation, which is crucial for hydrogels for wound healing applications. To take advantage of the regenerative activity of NAC while avoiding hampering the hemostasis stage during wound healing, we modified gelatin-NAC with the methacrylate-containing polymers 2-hydroxyethyl methacrylate (H) and poly(ethylene glycol) methyl ether methacrylate (P) to produce Gel-HP-NAC. These hydrogels clotted more blood and faster than Gel and Gel-NAC hydrogels, while maintaining fluid absorption properties adequate to promote wound healing. Similarly, there were more viable human skin fibroblasts after 10 days cultured in Gel-HP-NAC compared with Gel and Gel-NAC. A mouse full-thickness skin wound model demonstrated that Gel-HP-NAC hydrogels improved the wound healing process as compared to the untreated group as proved by the increased wound closure rates and re-epithelialization. Histology of the biopsied tissues indicated more organized collagen deposits on the wounds treated with either Gel-HP-NAC or Gel-NAC than untreated wounds. Our results show that modification of NAC-containing hydrogels through methacrylate-containing polymers improved their wound healing properties, including blood-clotting, and demonstrate the potential of Gel-HP-NAC hydrogels for wound treatment and tissue regeneration.

中文翻译：

通过用含甲基丙烯酸酯的聚合物修饰N-乙酰基半胱氨酸改善水凝胶的伤口愈合特性

具有抗氧化活性的水凝胶可显着改善护理标准，因为它们可促进伤口的有效愈合，即再生。ñ-乙酰半胱氨酸（NAC）是一种抗氧化剂氨基酸衍生物，可促进完整的组织恢复。但是，NAC具有抗凝特性，也可能会阻碍血液凝结，这对于伤口愈合应用的水凝胶至关重要。为了利用NAC的再生活性，同时避免在伤口愈合过程中阻碍止血阶段，我们用含甲基丙烯酸酯的聚合物2-甲基丙烯酸羟乙酯（H）和聚乙二醇甲基醚甲基丙烯酸酯（P）改性了明胶-NAC。生产Gel-HP-NAC。这些水凝胶比Gel和Gel-NAC水凝胶凝结更多的血液，速度更快，同时保持足够的液体吸收特性以促进伤口愈合。同样，与Gel和Gel-NAC相比，在Gel-HP-NAC中培养10天后，人类皮肤成纤维细胞的存活率更高。小鼠全层皮肤伤口模型表明，与未治疗组相比，Gel-HP-NAC水凝胶改善了伤口愈合过程，这通过增加伤口闭合率和重新上皮形成证明。活检组织的组织学表明，与未治疗的伤口相比，在用Gel-HP-NAC或Gel-NAC处理的伤口上更有组织的胶原蛋白沉积。我们的结果表明，通过含甲基丙烯酸酯的聚合物修饰含NAC的水凝胶可改善其伤口愈合特性（包括凝血），并证明Gel-HP-NAC水凝胶在伤口治疗和组织再生中的潜力。活检组织的组织学表明，与未治疗的伤口相比，在用Gel-HP-NAC或Gel-NAC处理的伤口上更有组织的胶原蛋白沉积。我们的结果表明，通过含甲基丙烯酸酯的聚合物修饰含NAC的水凝胶可改善其伤口愈合特性（包括凝血），并证明Gel-HP-NAC水凝胶在伤口治疗和组织再生中的潜力。活检组织的组织学表明，与未治疗的伤口相比，在用Gel-HP-NAC或Gel-NAC处理的伤口上更有组织的胶原蛋白沉积。我们的结果表明，通过含甲基丙烯酸酯的聚合物修饰含NAC的水凝胶可改善其伤口愈合特性（包括凝血），并证明Gel-HP-NAC水凝胶在伤口治疗和组织再生中的潜力。

更新日期：2020-11-12

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