Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
Hendrix Burn and Wound Healing Laboratory, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Int J Mol Sci. 2023 Sep 14;24(18):14095. doi: 10.3390/ijms241814095.
Wound therapies involving gene delivery to the skin have significant potential due to the advantage and ease of local treatment. However, choosing the appropriate vector to enable successful gene expression while also ensuring that the treatment's immediate material components are conducive to healing itself is critical. In this study, we utilized a particulate formulation of the polymer chitosan (chitosan particles, CPs) as a non-viral vector for the delivery of a plasmid encoding human CA5-HIF-1α, a degradation resistant form of HIF-1α, to enhance wound healing. We also compared the angiogenic potential of our treatment (HIF/CPs) to that of chitosan particles containing only the plasmid backbone (bb/CPs) and the chitosan particle vector alone (CPs). Our results indicate that chitosan particles exert angiogenic effects that are enhanced with the human CA5-HIF-1α-encoded plasmid. Moreover, HIF/CPs enhanced wound healing in diabetic db/db mice ( < 0.01), and healed tissue was found to contain a significantly increased number of blood vessels compared to bb/CPs ( < 0.01), CPs ( < 0.05) and no-treatment groups ( < 0.01). Thus, this study represents a method of gene delivery to the skin that utilizes an inherently pro-wound-healing polymer as a vector for plasmid DNA that has broad application for the expression of other therapeutic genes.
基于局部治疗的优势和便利性，涉及向皮肤递呈基因的伤口疗法具有巨大的潜力。然而，选择合适的载体以实现成功的基因表达，同时确保治疗即时的材料成分有利于伤口愈合本身，是至关重要的。在这项研究中，我们利用聚合物壳聚糖的颗粒制剂（壳聚糖颗粒，CPs）作为非病毒载体，递呈编码人 CA5-HIF-1α的质粒，CA5-HIF-1α 是一种具有抗降解能力的 HIF-1α 形式，以增强伤口愈合。我们还比较了我们的治疗方法（HIF/CPs）与仅包含质粒骨架的壳聚糖颗粒（bb/CPs）和壳聚糖颗粒载体（CPs）的血管生成潜力。我们的结果表明，壳聚糖颗粒具有血管生成作用，而携带人 CA5-HIF-1α 编码质粒的壳聚糖颗粒则增强了这种作用。此外，HIF/CPs 增强了糖尿病 db/db 小鼠的伤口愈合（<0.01），与 bb/CPs（<0.01）、CPs（<0.05）和无治疗组（<0.01）相比，愈合组织中含有显著增加数量的血管。因此，这项研究代表了一种将基因递送至皮肤的方法，它利用固有促伤口愈合的聚合物作为质粒 DNA 的载体，对于表达其他治疗基因具有广泛的应用。
