(674g) Using Rheology to Quantify the Effects of Injectable Collagenase Treatments on Strength and Viscoelasticity of Mammalian Tissues
AIChE Annual Meeting
2019
2019 AIChE Annual Meeting
Materials Engineering and Sciences Division
Biomaterials
Thursday, November 14, 2019 - 2:18pm to 2:36pm
Biological tissues are
complex composite materials whose mechanical properties are often difficult to
measure by traditional techniques. Quantification of bulk tissue properties,
such as modulus and viscoelasticity, can be used in disease diagnosis and
design of novel therapies. We demonstrate the ability to measure multiple types
of mammalian tissues, with elastic moduli ranging from 100-10,000 Pa, by dynamic
oscillatory rheology on a commercially-available rheometer. We begin by showing
data collected from reduction mammoplasty human breast tissues isolated from
multiple individuals and demonstrate that rheology can quantify tissue
variability. Repeated freeze-thaw studies show the effect of sample history and
highlight the need for consistent protocols for handling biological samples. We
then move on to show results from two case studies involving tissue digestion
by injected collagenase enzymes and illustrate how rheology can be used to
quantify treatment efficacy. In the first, we used rheology to measure
degradation by liberase of xenograft human breast cancer tumors grown in
athymic nude mice. In the second, we used both rheology and histology to
quantify the degree of in-vivo degradation of human uterine fibroid
tissue by collagenase Clostridium histolyticum. In both studies, we
co-injected Liquogel (LQG), a thermoresponsive polymer that transitions upon
heating from an injectable solution to a gel, to reduce diffusion of
collagenase from the injection site. All tissues showed gel-like rheological
behavior. We calculated average tissue moduli and viscoelasticity (tan δ) for
all tissues. We observed that injections of LQG & collagenase significantly
reduced tissue modulus compared to both buffer controls and free collagenase injections.
Injection of LQG & collagenase also significantly increased viscoelasticity.
Finally, we demonstrate how atomic force microscopy measurements and
histological staining of parallel tissue samples can be used alongside
rheological measurements to gain a more complete understanding of treatment
effects on tissues.
Figure 1. Enzymatic
treatment effects after three days post-injection on the A) elastic modulus and
B) viscoelasticity of xenograft mouse breast cancer tumors, showing the
differences between samples from the tumor center vs. edge. The combined
LQG+Lib treatment caused the largest reduction in modulus at both the center
and the edge, while the viscoelasticity remained unaffected by all treatments.
Figure 2. Time-dependent
treatment effects on the A) elastic modulus and B) viscoelasticity of human
uterine fibroid tissue implanted in mice for in vivo incubation and
extracted after one, two, or seven days. The combined LQG+CCH treatment caused
a significant reduction in modulus and increase in viscoelasticity after seven
days.