TY - JOUR
T1 - Miniaturized Needle Array-Mediated Drug Delivery Accelerates Wound Healing
AU - Samandari, Mohamadmahdi
AU - Aghabaglou, Fariba
AU - Nuutila, Kristo
AU - Derakhshandeh, Hossein
AU - Zhang, Yuteng
AU - Endo, Yori
AU - Harris, Seth
AU - Barnum, Lindsay
AU - Kreikemeier-Bower, Craig
AU - Arab-Tehrany, Elmira
AU - Peppas, Nicholas A.
AU - Sinha, Indranil
AU - Tamayol, Ali
N1 - Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/4/21
Y1 - 2021/4/21
N2 - 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.
AB - 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.
KW - VEGF
KW - intradermal drug delivery
KW - miniaturized needle arrays
KW - wound contraction
KW - wound healing
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U2 - 10.1002/adhm.202001800
DO - 10.1002/adhm.202001800
M3 - Article
C2 - 33586339
AN - SCOPUS:85100863408
SN - 2192-2640
VL - 10
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 8
M1 - 2001800
ER -