Article by Shanti E. Mehta
Graphic design by Jennifer Barolet
According to the World Health Organization, over 180,000 people die from burns each year1. Advancements in medicine have led to a greater standard of care for burn patients, however, wound healing and burn coverage is an essential factor in determining survival2. This summer I have had the privilege to work under Dr. Marc G. Jeschke in his lab, at Sunnybrook Research Institute.
Autologous skin grafts (i.e. the individual’s own tissue) are the current standard of care for severe burn injuries, however, there is often an insufficient amount of viable donor skin3 to cover the wound. Allographs are also used but pose the risk of graft rejection and infection4. The limitations posed by autografts and allografts have led to the development of dermal substitutes through bioprinting. My project focused on bioprinting human stem-cell laden extracellular matrix hydrogel for skin bioengineering. Throughout the summer I have worked on developing bio-ink and performing in vitro characterization as well as developing a bioprinting platform. The end goal of this research is to be able to obtain mesenchymal stem cells from burn patients, and bio-print personalized skin to be used in grafts, thus eliminating the drawbacks associated with both autographs and allographs.
The results I have obtained thus far focus primarily on characterization studies, specifically the morphological, histological, and biological characteristics of the bio-ink. It has been demonstrated that porcine tissue can successfully be decellularized while reserving a minimum of 40% of collagen content when compared to native tissue, which is essential in the development of bio-ink. We were able to show that fibroblasts can proliferate over time using the decellularized extracellular matrix as a scaffold, while also maintaining cell viability. This is important because fibroblasts produce collagen and extracellular matrix components, and are important for building and repairing skin’s structural framework. In the bioprinting platform development, we proved that pH-adjusted hydrogel can be extruded from a bioprinter.
Working on this project provided me with numerous learning opportunities, from zoom lab meeting presentations to hands-on work and learning lab techniques. I have learned that failure is part of success – not every experiment will go as planned, but these challenges only further developed my skills by providing an opportunity to understand, question, and learn from what went wrong the first time, so I can determine areas to be improved upon. I have learned so much about burn care and treatment, including future directions in research, such as using computational fluid dynamics to determine important rheological properties before the bioprinting process to maintain optimal cell viability and quality of the printed construct5. I am thankful for the guidance and support I have received this summer at the lab, specifically from Yufei Chen, and I am confident the skills I have acquired and lessons I have learned will serve me in the years to come.
My project is far from over, and next steps include continuing rheological characterization studies and performing simulation studies to examine the stressors experienced by the bio-ink during the printing process. With my findings thus far, in the future, I hope that burn-derived mesenchymal stem cells and keratinocytes can be incorporated to form biolayer skin substitutes for burn patients.
- World Health Organization, Burns. 2018 Mar 6; Available from: https://www.who.int/news-room/fact-sheets/detail/burns
- Jeschke, M.G., van Baar, M.E., Choudhry, M.A. et al. Burn injury. Nat Rev Dis Primers, 2020 Feb; available from: https://doi.org/10.1038/s41572-020-0145-5
- Sheikholeslam M, Wright MEE, Jeschke MG, Amini-Nik S. Biomaterials for Skin Substitutes. Advanced Healthcare Materials, available from 2018 Mar; Available from: 10.1002/adhm.201700897
- Amini-Nik S, Dolp R, Eylert G, Datu AK, Parousis A, Blakeley C, Jeschke MG. Stem cells derived from burned skin – The future of burn care. The Lancet, 2018 Nov; Available from: 10.1016/j.ebiom.2018.10.014
- Magalhães, Isabela & Oliveira, Patrícia & Dernowsek, Janaína & Las Casas, Estevam & las Casas, Marina. (2019). Investigation of the effect of nozzle design on rheological bioprinting properties using computational fluid dynamics. Matéria (Rio de Janeiro). 2019 Jan; Available from 10.1590/s1517-707620190003.0714.