This past friday was the final day of my Summer Undergraduate Research Fellowship with the Laboratory for Regenerative Wound Healing at Cincinnati Children’s Hospital Medical Center. I gave a poster presentation along with over 150 other students at 9:00am, which detailed my summers work and what I was able to accomplish. I am proud to say that I was awarded honorable mention, but the true award to me was being able to share my project with so many other people. In only a couple hours, I had over a dozen students, parents, research faculty, and doctors visit my poster. Now, I would like to share with you what I have done and find so interesting.
Looking at the big picture, we know that each year in the developed world about 100 million patients acquire scars, and the global value is undoubtedly higher. Scarring can be an emotional burden and lead to significant financial costs, which can be the result of aesthetic, physical, or psychological consequences. Currently, there is no effective scar therapy. With that in mind, our lab uses the fetal response to injury as a roadmap to achieve regenerative wound healing. What does that mean? If you were to make an incision or the fetus suffered an injury, it would heal without a scar. However, we obviously can’t do that, so what is the difference between the fetus and adults? Our lab has shown a significant role for IL-10 in the fetal regenerative response. Additionally, we have shown that viral over-expression of IL-10 in adult wounds results in scarless wound healing. However, there are some translational issues with this. Hence, our lab developed a sustained delivery hydrogel (HH10) that overcomes the translatable issues of gene therapy. The last thing that I want to mention is that currently, there is no quantifiable method to assess scars on a histologic scale. Wound healing relies heavily on histology, which is basically staining cells and looking at them under a microscope.
If we develop a novel method to histologically assess dermal scarring, we can validate the properties of HH10 in cutaneous wounds AIM 1: Develop a new computational method of scar analysis compared to the regenerative benchmark of skin AIM 2: Validation of the extended release hydrogel using an innovative scar assessment tool
METHODS: AIM 1
My first priority for the summer was to develop a new method for analyzing scars histologically. To do this, I ordered mice and (following all ethical guidelines and standard protocol) made 4mm wounds on the backs of the mice. After 28 days, I collected the wounds, and looked at the differences between skin and scars (n=20/group). With these images, I was able to establish 5 parameters or statistical differences between skin and scar. These were height of the epidermis, orientation of keratinocytes (the main cell line in the epidermis), scar area, the number of dermal appendages (functional aspect of the skin, includes hair follicles, sweat glands), and the vascular density (presence of vessels).
METHODS: AIM 2
After I discovered these parameters, I wanted to test the labs hydrogel using this scar assessment scale. I followed the same basic protocol, but this time, after I made the wounds, I inserted the various treatment groups. Gel Control has all of the components in HH10, except IL-10. After 28 days, I collected the wounds and analyzed them using these parameters.
I was able to quantifiably define a scar based on 5 parameters, as the skin and scar are statistically different. When you look histologically, you will find that HH10 restores scar parameters to levels observed in normal unwounded skin. Also, HH10 is statistically similar to gene transfer by viral over-expression. HH10 showed improved collagen arrangement, number of dermal appendages, and epidermal structure compared to Gel Control and scar.
This scar assessment tool is a novel method, which has the potential to be used as the future benchmark in determining the efficacy of preclinical anti-scarring therapeutics to achieve regenerative repair. HH10 is a safe, non-viral mediated delivery system that restores epidermal and dermal scar parameters to the levels observed in normal unwounded skin. Lastly, the potential therapeutic benefits of HH10 extend beyond cosmetic benefit, but may apply to a broad range of diseases characterized by excessive fibroplasia, including post-surgical wounds, intra-abdominal adhesions, pathologic scars and organ fibrosis.
It has been a fantastic summer full of learning and growth. I just want to take a moment to acknowledge the Center for Engaged Learning and Teaching, because without the CELT Summer Internship Award, I wouldn’t have had the successful summer I wrote about in this post.