Gefen A, van Nierop B, Bader DL, Oomens CW, et al.
Journal of biomechanics. Date of publication 2008 Jan 1;volume 41(9):2003-12.
1. J Biomech. 2008;41(9):2003-12. doi: 10.1016/j.jbiomech.2008.03.039. Epub 2008 May
23.
Strain-time cell-death threshold for skeletal muscle in a tissue-engineered model
system for deep tissue injury.
Gefen A(1), van Nierop B, Bader DL, Oomens CW.
Author information:
(1)Department of Biomedical Engineering, Eindhoven University of Technology,
Eindhoven, Netherlands. gefen@eng.tau.ac.il
Deep tissue injury (DTI) is a severe pressure ulcer that results from sustained
deformation of muscle tissue overlying bony prominences. In order to understand
the etiology of DTI, it is essential to determine the tolerance of muscle cells
to large mechanical strains. In this study, a new experimental method of
determining the time-dependent critical compressive strains for necrotic cell
death (E(zz)(c)(t)) in a planar tissue-engineered construct under static loading
was developed. A half-spherical indentor is used to induce a non-uniform,
concentric distribution of strains in the construct, and E(zz)(c)(t) is
calculated from the radius of the damage region in the construct versus time. The
method was employed to obtain E(zz)(c)(t) for bio-artificial muscles (BAMs)
cultured from C2C12 murine cells, as a model system for DTI. Specifically,
propidium iodine was used to fluorescently stain the development of necrosis in
BAMs subjected to strains up to 80%. Two groups of BAMs were tested at an
extracellular pH of 7.4 (n=10) and pH 6.5 (n=5). The lowest strain levels causing
cell death in the BAMs were determined every 15min, during 285-min-long trials,
from confocal microscopy fluorescent images of the size of the damage regions.
The experimental E(zz)(c)(t) data fitted a decreasing single-step sigmoid of the
Boltzmann type. Analysis of the parameters of this sigmoid function indicated a
95% likelihood that cells could tolerate engineering strains below 65% for 1h,
whereas the cells could endure strains below 40% over a 285min trial period. The
decrease in endurance of the cells to compressive strains occurred between 1-3h
post-loading. The method developed in this paper is generic and suitable for
studying E(zz)(c)(t) in virtually any planar tissue-engineered construct. The
specific E(zz)(c)(t) curve obtained herein is necessary for extrapolating
biological damage from muscle-strain data in biomechanical studies of pressure
ulcers and DTI.
DOI: 10.1016/j.jbiomech.2008.03.039
PMID: 18501912 [Indexed for MEDLINE]
