Delivering proteins to human skin to alter its identity, via a pH responsive microneedle
File(s)
Author(s)
Abbas, Attiya
Type
Thesis or dissertation
Abstract
Human skin is heterogeneous. As the interface between the outside world and our internal organs it is a vital barrier to external damage. On a single person, skin varies in thickness and stiffness across body sites, thus possessing various susceptibility to injury. From individual to individual, skin varies in colour and biological age further influencing disease risk and regeneration capacity. In this body of work, I discuss the nuances of skin properties impacted by body location, age, and colour. I present the development of a therapeutic device to prevent skin injury.
Firstly, it is known that skin thickness can vary depending on body site notably differing the most between plantar and nonplantar tissue. Nonplantar human skin is more susceptible to skin injury than plantar skin which is present on palm of hands and soles of feet. This is a critical concern for limb amputee patients that exhibit nonplantar stump site tissue. I investigated whether skin properties could be transformed with protein therapy; Wnt5a, by modulating the specific gene expression of nonplantar tissue to become plantar. I designed and engineered a microneedle (MN) device for optimal delivery of the Wnt5a protein and other drug candidates to the epidermal layer of the human skin as a potential therapeutic.
Next, in recent years the definition of ageing has become more convoluted with biological ageing being characterised as a scale of ageing that considerably varies depending on the individual. Several internal and external factors can drive biological ageing of the skin which impacts the properties of this vital organ. I explored the effect of a physiologically relevant environmental stimuli, UVA, on ex vivo human skin to assess changes in biological age and how that in turn influences skin injury. I investigated the preventative capacity of an anti-ageing protein, klotho, on UV impaired healing.
Firstly, it is known that skin thickness can vary depending on body site notably differing the most between plantar and nonplantar tissue. Nonplantar human skin is more susceptible to skin injury than plantar skin which is present on palm of hands and soles of feet. This is a critical concern for limb amputee patients that exhibit nonplantar stump site tissue. I investigated whether skin properties could be transformed with protein therapy; Wnt5a, by modulating the specific gene expression of nonplantar tissue to become plantar. I designed and engineered a microneedle (MN) device for optimal delivery of the Wnt5a protein and other drug candidates to the epidermal layer of the human skin as a potential therapeutic.
Next, in recent years the definition of ageing has become more convoluted with biological ageing being characterised as a scale of ageing that considerably varies depending on the individual. Several internal and external factors can drive biological ageing of the skin which impacts the properties of this vital organ. I explored the effect of a physiologically relevant environmental stimuli, UVA, on ex vivo human skin to assess changes in biological age and how that in turn influences skin injury. I investigated the preventative capacity of an anti-ageing protein, klotho, on UV impaired healing.
Version
Open Access
Date Issued
2024-05-31
Date Awarded
2024-09-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Higgins, Claire
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)