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Temporally controlled delivery of vascular therapeutics from a regenerative template for diabetic wound healing

Periodic Reporting for period 1 - VascColl (Temporally controlled delivery of vascular therapeutics from a regenerative template for diabetic wound healing)

Período documentado: 2015-05-01 hasta 2017-04-30

Diabetic patients can suffer from diabetic foot ulcer (DFU) wounds, which are complex wounds that may not heal. Devastatingly, even with treatment, this can ultimately result in amputation of the affected limb. One reason that these wounds are challenging to heal is that they do not step through the normal wound healing sequence. If a solution to effectively heal these wounds could be developed, it would dramatically increase the quality of life for patients affected by diabetic foot ulcers.
During this Marie Curie fellowship, the goal was to design a tissue engineering solution to treat diabetic foot ulcers, which would help guide the body in healing itself. The device used consists of a porous collagen biomaterial for cells to attach to and grow new tissue. In addition, small particles of gel containing proteins that can direct wound healing, can be incorporated into the collagen; when ultrasound is applied, the proteins are released. By releasing the proteins at specific time-points, the goal is to instruct the cells to progress normally through the wound healing stages. The overall objectives were to develop the device and to test the idea that delivering proteins at precise time-points can be used to co-ordinate and improve wound healing.
The overall scientific goals were achieved in the project – the device was developed and its ability to house and grow cells was demonstrated. Furthermore, the ability to release a model nanoparticle (i.e. non-therapeutic) from the scaffold, on-demand, was shown. In addition, an extensive study in vitro (i.e. outside the body) was performed using the collagen scaffolds and human cells to test whether the timing of protein delivery could affect the ability to grow and mature blood vessels.
During the course of the project, additional opportunities arose as a result of the fabrication techniques developed. In addition to the on-demand delivery scaffold described above, a magnetically responsive scaffold (that deforms in response to a magnet) was developed. This can be used to apply forces to cells within these scaffolds, potentially helping control their growth rate and behaviours.
The work completed as a Marie Skłowdowska Curie fellow has, to date, resulted in 4 journal articles, 9 conference talks, 13 poster presentations at conferences and 5 invited talks to date; 2 additional journal articles are currently under peer review.

(Note: Some results and details are omitted due to confidentiality).
The work in VascColl has resulted in a novel device that can deliver nanoparticles at precise timepoints within a biomaterial that already has proven regenerative potential. After the end of the project, work in my lab will continue on this device, which we hope will demonstrate the ability to deliver therapeutically-active nanoparticles. Ultimately, the aim is that the device will be able to direct the healing of diabetic foot ulcers (DFUs). 15 – 25% of the world’s diabetic population (over 400 million) is expected to get a foot ulcer at some point in their lifetime. These wounds dramatically affect patient quality of life; healing these ulcers would not only greatly improve patient well-being, but would also reduce the substantial economic burden associated with treating these ulcers.
VascColl Figure