T. Dohi1, J. Padmanabhan1, P. Than1, S. Akaishi3, M. Terashima2, N. Matsumoto3, R. Ogawa3, G. C. Gurtner1 1Stanford University,Department Of Surgery,Palo Alto, CA, USA 2Stanford University,Department Of Civil & Environmental Engineering,Palo Alto, CA, USA 3Nippon Medical School,Department Of Plastic, Reconstructive And Aesthetic Surgery,Bunkyo, TOKYO, Japan
Introduction: There is high morbidity, mortality, and cost related to fibroproliferative disorders. Of these, keloids are unique in that they progress beyond the original site of injury and form large, linear scars often of significantly different shape from the initial wound. The unknown pathophysiology, high rate of recurrence, and lack of effective treatment modalities makes keloid disease a challenging clinical problem. Progression beyond the original injury site and extension into normal peripheral skin highlights the zone between the keloid and surrounding skin as a target for investigation.
Methods: We analyzed posture-related changes in local strain in various human anatomic locations correlated with keloid formation (n=10). Additionally, we developed a finite element method (FEM) analytic model to study the effect of von Mises stress and true strain in keloid-containing regions of skin. We also performed targeted-molecular analysis of human keloid-containing skin samples to identify the key biochemical pathways involved in keloid progression (n=5).
Results: Anatomic regions prone to keloid formation are subject to high-levels of multidirectional posture-related strain. Focusing on these areas we created a model using finite element analysis and demonstrated that multidirectional loading leads to high true strain in the peripheral tissue surrounding the keloid. Furthermore, comparative immunohistochemical staining of human keloid tissue, peripheral tissue and control skin revealed that the peripheral tissue exhibits high levels of proliferation and altered mechanotransduction components including HSP27 and NFkB.
Conclusion: In summary, we describe a novel mechanism through which keloid disease may progress beyond the original wound site. Specifically, we show that changes in human posture result in elevated true strain in tissues immediately surrounding keloids in anatomic regions that are prone to keloid formation. We found that key mechanotransduction signaling pathways are altered in these regions, which may underlie the unique spread of keloid disease beyond the original wound site. These findings identify several molecular targets for therapy with potential for rapid clinical translation.