Department of Burn and Plastic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Acta Biomater. 2019 Dec;100:191-201. doi: 10.1016/j.actbio.2019.10.004. Epub 2019 Oct 4.
Excessive inflammation and reduced angiogenesis are two major obstacles in burn wound healing and skin regeneration. Here we report the fabrication and application of a sophisticated hydrogel from chemically modified hyaluronic acid (HA), dextran (Dex), and β-cyclodextrin (β-CD) integrating resveratrol (Res) and vascular endothelial growth factor (VEGF) plasmid as the anti-inflammatory and pro-angiogenic components for burn wounds. Firstly, covalent alterations were conducted to obtain methacrylic acid anhydride modified HA (HAMA), N-hydroxyethylacrylamide (HEAA) modified Dex (Dex-HEAA), and poly(ethylene glycol) methyl acrylate (526) modified β-CD (526-β-CD), respectively. Secondly, anti-inflammatory substance Res was embedded into the lipophilic central cavity of 526-β-CD to achieve a complex of 526-β-CD-Res. Then hydrogels with different HAMA, Dex-HEAA, and 526-β-CD-Res ratios were generated via UV irradiation. Lastly, plasmid DNA encoded with vascular endothelial growth factor (pDNA-VEGF) conjugating with polyethylenimine was loaded into the hydrogel scaffold. Combining the benefits of all components of the scaffold, the hydrogel embedded with Res and VEGF (Gel-Res/pDNA-VEGF) accelerated the splinted excisional burn wound healing, particularly by inhibiting inflammation response and promoting microvascular formation while being biocompatible. The Res and VEGF gene loaded hydrogel system can be considered as a promising wound dressing for the treatment of various types of wounds. STATEMENT OF SIGNIFICANCE: Combining the benefits of all components of the scaffold, the hydrogel embedded with Res and VEGF (Gel-Res/pDNA-VEGF) accelerated the splinted excisional burn wound healing, particularly by inhibiting inflammation response and promoting microvascular formation while being biocompatible. The Res and VEGF gene loaded hydrogel system can be considered as a promising wound dressing for the treatment of various types of wounds.
过度炎症和血管生成减少是烧伤创面愈合和皮肤再生的两个主要障碍。在这里，我们报告了一种由化学修饰的透明质酸（HA）、葡聚糖（Dex）和β-环糊精（β-CD）组成的复杂水凝胶的制备和应用，该水凝胶整合了白藜芦醇（Res）和血管内皮生长因子（VEGF）质粒，作为抗炎和促血管生成成分用于烧伤创面。首先，进行了共价修饰，分别得到甲基丙烯酰基酐修饰的透明质酸（HAMA）、N-羟乙基丙烯酰胺（HEAA）修饰的葡聚糖（Dex-HEAA）和聚乙二醇甲基丙烯酸酯（526）修饰的β-CD（526-β-CD）。其次，将抗炎物质 Res 嵌入到疏水性中央腔内的 526-β-CD 中，以实现 526-β-CD-Res 复合物。然后，通过紫外光照射生成具有不同 HAMA、Dex-HEAA 和 526-β-CD-Res 比例的水凝胶。最后，将编码血管内皮生长因子（pDNA-VEGF）的质粒 DNA 与聚乙烯亚胺偶联后载入水凝胶支架中。结合支架各组成部分的优势，负载 Res 和 VEGF 的水凝胶（Gel-Res/pDNA-VEGF）加速了夹板切除烧伤创面的愈合，特别是通过抑制炎症反应和促进微血管形成，同时具有生物相容性。负载 Res 和 VEGF 基因的水凝胶系统可被视为治疗各种类型创面的有前途的创面敷料。
