Department of Biomedical Engineering, University of Connecticut, Farmington, CT, 06030, USA.
Department of Biomedical Engineering and Neurosurgery, Johns Hopkins University, Baltimore, MD, USA.
Adv Healthc Mater. 2021 Apr;10(8):e2001800. doi: 10.1002/adhm.202001800. Epub 2021 Feb 15.
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.
阻止正常伤口愈合的一个主要障碍是血管生成不足，这会导致缺氧、代谢支持不良以及损伤后的生理反应失调。为了克服这一问题，已经证明输送血管生成因子，如血管内皮生长因子（VEGF），可以适度改善伤口愈合。在这里，探索了特种输送系统在控制伤口床药物分布方面的重要性，从而提高了愈合速度和质量。评估了两种真皮内药物输送系统，即微型针阵列（MNAs）和液体喷射注射器（LJIs），以比较有效输送 VEGF 进入伤口床。两种技术之间，药物的渗透深度和在组织中的分布有显著差异。首先在体外确认了这些系统高效输送药物的能力，然后在体内进行了评估。虽然局部给予 VEGF 的效果有限，但在糖尿病小鼠模型中真皮内给予 VEGF 可加速伤口愈合。为了评估该策略的转化可行性，在猪模型中评估了使用 MNAs 进行 VEGF 输送的益处。结果表明，该方法具有增强的血管生成、减少的伤口收缩和增加的再生。这些发现表明在伤口愈合中，治疗药物和输送策略都很重要。
