KPTC 206 5620 S. Ellis Avenue
5620 S. Ellis Avenue
Cells within load-bearing soft tissues sense and respond to diverse stimuli, including mechanobiological and immunobiological. Mechanical homeostasis is a ubiquitous process by which certain mechanical quantities are regulated to remain, within a range, near a preferred value, often called a set point. As an example, both flow-induced wall shear stress and pressure-induced intramural stress tend to be mechano-regulated to remain close to region-specific set-points in vascular mechanics. In some cases, inflammation can support mechanical homeostasis while in other cases it can prevent such homeostasis.
In this talk, we will consider two cases wherein it is important to model both the mechanical and the inflammatory signals and responses, illustrated here for blood vessels. In the first case, we will consider the in vivo development of a tissue engineered neovessel from an implanted polymeric implant. In the second case, we will consider the growth and remodeling of a native artery in a mouse model of induced hypertension. Although inflammation arises for very different reasons in these two cases, we shall see how a consistent constrained mixture model of growth and remodeling can be used to predict the evolving geometry, composition, and wall properties in both cases. Importantly, computational predictions in the tissue engineered case helped lead to US Food and Drug Administration (FDA) approval of a clinical trial of a promising technology for treating congenital heart defects in children, thus showing translational potential of immuno-mechanical computational models of tissue response. For more information, please find details presented elsewhere [1-4].
 Szafron J, Khosravi R, Reinhardt J, Best CA, Bersi MR, Yi T, Breuer CK, Humphrey JD (2018) Immuno-driven and mechano-mediated neotissue formation in tissue engineered vascular grafts. Annl Biomed Engr 46: 1938-1950.
 Latorre M, Bersi MR, Humphrey JD (2019) Computational modeling predicts immuno-mechanical mechanisms of maladaptative aortic remodeling in hypertension. Int J Engr Sci 14: 35-46.
 Drews J, Pepper VA, Best CA, Szafron JM, …, Humphrey JD, Shinoka T, Breuer CK (2020) Spontaneous reversal of stenosis in tissue-engineered vascular grafts. Sci Transl Med 12:eaax6919.
 Spronck B, Latorre M, Wang M, Mehta S, Caulk AW, Ren P, Ramachandra AB, Murtada S-I, Rojas A, He C-S, Jiang B, Bersi MR, Tellides G, Humphrey JD (2021) Excessive adventitial stress drives inflammation-mediated fibrosis in hypertensive aortic remodeling in mice. J R Soc Interface 18:20210336.