Biomechanical Restoration Potential of Pentagalloyl Glucose after Arterial Extracellular Matrix Degeneration

Abstract

The objective of this study was to quantify pentagalloyl glucose (PGG) mediated biomechanical restoration of degenerated extracellular matrix (ECM). Planar biaxial tensile testing was performed for native (N), enzyme-treated (collagenase and elastase) (E), and PGG (P) treated porcine abdominal aorta specimens (n = 6 per group). An Ogden material model was fitted to the stress-strain data and finite element computational analyses of simulated native aorta and aneurysmal abdominal aorta were performed. The maximum tensile stress of the N group was higher than that in both E and P groups for both circumferential (43.78 ± 14.18 kPa vs. 10.03 ± 2.68 kPa vs. 13.85 ± 3.02 kPa; p = 0.0226) and longitudinal directions (33.89 ± 8.98 kPa vs. 9.04 ± 2.68 kPa vs. 14.69 ± 5.88 kPa; p = 0.0441). Tensile moduli in the circumferential direction was found to be in descending order as N > P > E (195.6 ± 58.72 kPa > 81.8 ± 22.76 kPa > 46.51 ± 15.04 kPa; p = 0.0314), whereas no significant differences were found in the longitudinal direction (p = 0.1607). PGG binds to the hydrophobic core of arterial tissues and the crosslinking of ECM fibers is one of the possible explanations for the recovery of biomechanical properties observed in this study. PGG is a beneficial polyphenol that can be potentially translated to clinical practice for preventing rupture of the aneurysmal arterial wall.

Keywords: aneurysm; aorta; biomechanics; enzyme; pentagalloyl glucose.

Figure 1

Exemplary schematic for specimen procurement. Each specimen consisted of a cylindrical ring approximately 7 mm long, which were subject to planar biaxial tensile testing. N = 6 specimens per group were tested using a CellScale BioTester^® while submerging the specimen in saline solution at 37 °C.

Figure 2

Biomechanical parameters evaluated from the stress–strain curves generated from biaxial mechanical testing of porcine abdominal aorta specimens. (A) Schematic for calculation of area under the curve (AUC) and maximum tensile stress (${\sigma }_{max}$). (B) Procedure for calculation of anisotropy index ($AI$) at each reference stress level, as reported in [39,40]. The reference stresses for each specimen were calculated by estimating 33rd, 66th, and 95th percentiles of ${\sigma }_{max}$ in each stress–strain curve.

Figure 3

Geometric models and their dimensions for the (A) native abdominal aorta (NAA) and (B) aneurysmal abdominal aorta (AAA).

Figure 4

Biomechanical parameters for the native (N), elastase-digested (E), and PGG-treated (P) porcine abdominal aorta specimens, which are represented as mean ± SEM. Maximum stress (kPa) is displayed in both circumferential (${\sigma }_{max,C}$) (A) and longitudinal orientations (${\sigma }_{max,L}$) (B). (C,D) tensile moduli (TM) (kPa) and (E,F) area under the curve (AUC) (kPa) for both circumferential and longitudinal directions, respectively. *denotes significance across the groups (p < 0.05).

Figure 5

An assessment of the recovery of biomechanical properties by normalizing the enzymatic- and PGG-based biomechanical parameters to their native equivalents. We observe an increasing trend in ${\sigma }_{max}$ (A,B) and TM (C,D) for both circumferential and longitudinal orientations, respectively. AUC for both orientations exhibited similar but limited increase in strain energy (E,F), thereby indicating a conservation of elastic energy.

Figure 6

Ogden model fitting with the corresponding experimental stress–strain curves for an exemplary specimen of the native (N), enzyme (E), and PGG treatment (P) groups.

Figure 7

Wall stress spatial distribution for three exemplary FEA models (anterior view): (A) Native, (B) enzyme and (C) PGG treated. The Ogden hyperelastic constitutive material was utilized for the FEA simulations and a 100 mmHg intraluminal pressure was applied to the models. The upper limit of the stress legend was lowered to emphasize the differences across the three groups at the midsection.