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Abstract：
A major impediment preventing normal wound healing is insufficient vascularization, which causes hypoxia, poor metabolic support, and dysregulated physiological responses to injury. To combat this, the delivery of angiogenic factors, such as vascular endothelial growth factor (VEGF), has been shown to provide modest improvement in wound healing. Here, the importance of specialty delivery systems is explored in controlling wound bed drug distribution and consequently improving healing rate and quality. Two intradermal drug delivery systems, miniaturized needle arrays (MNAs) and liquid jet injectors (LJIs), are evaluated to compare effective VEGF delivery into the wound bed. The administered drug\'s penetration depth and distribution in tissue are significantly different between the two technologies. These systems\' capability for efficient drug delivery is first confirmed in vitro and then assessed in vivo. While topical administration of VEGF shows limited effectiveness, intradermal delivery of VEGF in a diabetic murine model accelerates wound healing. To evaluate the translational feasibility of the strategy, the benefits of VEGF delivery using MNAs are assessed in a porcine model. The results demonstrate enhanced angiogenesis, reduced wound contraction, and increased regeneration. These findings show the importance of both therapeutics and delivery strategy in wound healing.
摘要：
阻止正常伤口愈合的主要障碍是血管形成不足，导致缺氧，不良的代谢支持，和对损伤的生理反应失调。为了解决这个问题，血管生成因子的传递，如血管内皮生长因子（VEGF），已被证明在伤口愈合方面提供适度的改善。这里,探讨了特殊给药系统在控制伤口床药物分布，从而提高愈合率和质量方面的重要性。两种皮内给药系统,小型化针头阵列（MNA）和液体喷射注射器（LJIs），评估以比较有效的VEGF递送到伤口床中。两种技术之间给药的渗透深度和在组织中的分布明显不同。首先在体外确认这些系统有效药物递送的能力,然后在体内评估。虽然局部施用VEGF显示出有限的有效性，糖尿病小鼠模型中VEGF的皮内递送加速伤口愈合。为了评估战略的转化可行性，在猪模型中评估使用MNA递送VEGF的益处。结果表明血管生成增强，减少伤口收缩，增加再生。这些发现显示了治疗和递送策略在伤口愈合中的重要性。
