How hydrogel inclusions modulate the local mechanical response in early and fully formed post-infarcted myocardium | Academic Article individual record
abstract

Expansion of myocardium after myocardial infarction (MI) has long been identified as the primary mechanism that progresses adverse left ventricular (LV) remodeling towards heart failure and death. Direct injection of hydrogels into the myocardium to mechanically constrain the infarct has demonstrated promise in limiting its remodeling and expansion. Despite early successes, there remain open questions in the determination of optimal hydrogel therapies, key application characteristics for which include injected polymer volume, stiffness, and spatial placement. Addressing these questions is complicated by the substantial variations in infarct type and extent, as well as limited understanding of the underlying mechanisms. Herein, we present an investigation on how hydrogel inclusions affect the effective stiffness and strain fields in myocardium using full three-dimensional (3D) finite element simulations of early and late post-MI time points. We based our analysis on triaxial mechanical and structural measurements from cuboidal specimens of LV post-infarcted myocardium, 0 and 4 weeks post-MI, injected with a dual-crosslinking hyaluronic acid-based hydrogel. Simulations included multiple deformation modes that spanned the anticipated physiological range in order to assess the effects of variations in inclusion size, location, and modulus on tissue-level myocardial mechanics. We observed significant local stiffening in the hydrogel-injected specimens that was highly dependent on the volume and mechanical properties of the injected hydrogel. Simulations revealed that the primary effect of the injections under physiological loading was a reduction in myocardial strain. This result suggests that hydrogel injections reduce infarct expansion by limiting the peak strains over the cardiac cycle. Overall, our study indicated that modulation of the effective tissue stiffness and corresponding strain reduction are governed by the volume and stiffness of the hydrogel, but relatively insensitive to precise placement. These findings provide important insight into mechanisms for ameliorating post-MI remodeling, as well as guidance for the future design of post-MI therapies.

author list (cited authors)
Li, D. S., Avazmohammadi, R., Rodell, C. B., Hsu, E. W., Burdick, J. A., Gorman, J. H., Gorman, R. C., & Sacks, M. S.
publication date
2020
publisher
Elsevier bv Publisher
published in
keywords
  • Hydrogel Injection
  • Myocardial Infarction
  • Finite Element Modeling
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0.5

citation count

0