Nanoparticle Systems for Pressure Wound Healing

Project Details

Description

Individuals who suffer from paralysis subsequent to spinal cord injury (SCI) also lack sensation below the level of injury. As a result, they are not aware of impending tissue damage that may occur due to prolonged and/or excessive pressure. Normal individuals constantly shift their weight -- even unconsciously -- to relieve discomfort that occurs when sitting or lying in the same position for a prolonged period. In contrast, this does not occur in SCI patients who are confined to a wheel chair because do not feel anything and do not have motor control. As a result, these patients develop deep wounds around bony prominences where body weight is concentrated while they are sitting or lying. There are ~17,000 new cases of SCI reported each year in United States (including 12% of Veterans of the US Armed Forces), and ~30%-40% of these patients develop such wounds (also known as 'pressure sores'). Furthermore, such wounds exhibit a 60%-85% rate of re-occurrence. There is also evidence that blood flow regulation is impaired in these individuals, which likely contributes to the propensity of developing such wounds in SCI patients. There is a need to develop new therapies that promote healing of such wounds and lead to better quality of the healed wound so that it is less likely to re-occur.

Virtually all information related to the incidence of pressure sores comes from human clinical data. Due to the variability that is inherent to the human population, as well as ethical issues, there has been a need to develop a reliable and clinically relevant animal model to better understand the mechanisms that lead to the generation of pressure sores, as well as for testing potential new therapies before human trials. We have recently developed such a model in mice, whereby a pressure sore can be experimentally induced by applying strong magnets onto a skinfold on the back of mice. In this proposal, we plan to use this model to test the effect of locally applied factors that promote the growth of blood vessels. We hypothesize that by increasing blood flow in the wound using such factors, wound healing will be faster and will lead to a better scar, thus reducing the chance for the wound to subsequently reopen.

The main objective of this proposal is to develop new compounds that increase blood vessel formation -- and therefore blood flow -- when applied topically onto pressure sores. The compounds consist of known natural peptides that have known relevant biological activity, which will be coupled with other naturally occurring peptides that have the ability to self-assemble into nanoparticles. The resulting nanoparticles are more stable, have a long-lasting effect, such that they require a single application. We will test these compounds in our animal model to determine whether they do increase blood flow in the wound and whether this results in faster and improved wound healing.

Successful completion of this study will lead to a better understanding of the impact of SCI on blood flow regulation in wounds and the resulting impact on wound healing. This information will be helpful for the management of SCI patients and for the development of new therapies to help chronic or difficult-to-heal-wounds, a major secondary complication of SCI. Although this is mainly a basic science investigation, there is high potential for translation to the clinical realm. The main deciding factor to estimate the time scale to commercialization is the regulatory process, which generally takes several years. In our case, this process may be facilitated because all components of our therapeutic compounds are naturally occurring peptides; therefore, the risk of harm to the patient is minimized. Overall, this project addresses the ongoing 'Getting to Zero' initiative at the Veterans Administration to develop new methods to prevent and treat pressure ulcers.

StatusFinished
Effective start/end date8/1/177/31/20

Funding

  • Congressionally Directed Medical Research Programs: $617,559.00

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