Conditioning irradiated tissue for increasing vascularity
Inventors
WAN, Derrick C. • GURTNER, Geoffrey C. • Longaker, Michael T.
Assignees
Leland Stanford Junior University
Publication Number
US-12303475-B2
Publication Date
2025-05-20
Expiration Date
2038-09-12
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Abstract
Methods of increasing perfusion and vascularity in irradiated tissue and of increasing retention of fat cells in a fat graft in irradiated tissue by applying an effective amount of DFO to the irradiated tissue at a treatment site. The DFO may be administered transdermally.
Core Innovation
The invention provides a method for increasing vascularity and perfusion in irradiated tissue, which addresses the complications arising from radiation-induced hypovascularity, fibrosis, and atrophy that hinder successful reconstructive procedures such as fat grafting. This method involves applying an effective amount of deferoxamine (DFO), either through injection under the dermis or via transdermal application, prior to fat grafting at the treatment site to improve the tissue environment.
By preconditioning irradiated tissue with DFO, the method increases local blood perfusion and vascularity, resulting in improved retention and viability of fat grafts in tissues previously damaged by radiation. DFO administration is shown, through both injection and transdermal delivery, to stabilize hypoxia-inducible factor-1 alpha (HIF-1α), promoting the expression of angiogenic factors and enhancing the recruitment of endothelial progenitor cells, thereby reversing radiation-induced hypovascularity.
The invention also encompasses methods for increasing collagen deposition and reducing stiffness in irradiated tissue, as well as improving recipient site quality prior to fat grafting. Importantly, the use of DFO, including in nanoparticle or controlled-release formulations, enables flexibility in administration and may offer a less invasive and more patient-tolerable alternative to serial injections. The improved tissue environment achieved by DFO treatment is directly associated with better outcomes in soft tissue reconstruction following radiation injury.
Claims Coverage
The patent contains one independent claim covering one inventive feature.
Transdermal application of deferoxamine (DFO) to increase blood perfusion in irradiated tissue
A method of increasing blood perfusion in irradiated tissue by: - Applying an effective amount of deferoxamine (DFO) transdermally to the irradiated tissue at a treatment site. - Resulting in an increase in blood perfusion of the irradiated tissue at the treatment site. Dependent claims further specify applying DFO using a transdermal delivery device to the tissue surface, optionally with DFO encapsulated in reverse micelles, and applying DFO in multiple discrete doses.
The claim coverage centers on using transdermal delivery of DFO to improve blood perfusion in irradiated tissue, with further details provided by dependent claims regarding delivery devices, encapsulation, and dosing.
Stated Advantages
The method increases vascularity and perfusion in irradiated tissue, thereby improving the tissue environment for subsequent fat grafting.
Preconditioning with DFO improves retention and viability of fat grafts in irradiated tissue.
Transdermal delivery of DFO offers a less invasive and potentially better-tolerated approach compared to serial injections.
DFO treatment may reduce tissue stiffness after radiation therapy.
Documented Applications
Increasing perfusion and vascularity in irradiated tissue to enhance the retention of fat grafts for soft tissue reconstruction.
Improving outcomes in soft tissue reconstructive procedures after radiation therapy.
Reducing stiffness in irradiated tissue as measured by stress/strain curves (Young's Modulus).
Increasing collagen deposition in skin within irradiated tissue.
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