Porcine incisional hernia model: Evaluation of biologically derived intact extracellular matrix repairs

Abstract

We compared fascial wounds repaired with non-cross-linked intact porcine-derived acellular dermal matrix versus primary closure in a large-animal hernia model. Incisional hernias were created in Yucatan pigs and repaired after 3 weeks via open technique with suture-only primary closure or intraperitoneally placed porcine-derived acellular dermal matrix. Progressive changes in mechanical and biological properties of porcine-derived acellular dermal matrix and repair sites were assessed. Porcine-derived acellular dermal matrix-repaired hernias of additional animals were evaluated 2 and 4 weeks post incision to assess porcine-derived acellular dermal matrix regenerative potential and biomechanical changes. Hernias repaired with primary closure showed substantially more scarring and bone hyperplasia along the incision line. Mechanical remodeling of porcine-derived acellular dermal matrix was noted over time. Porcine-derived acellular dermal matrix elastic modulus and ultimate tensile stress were similar to fascia at 6 weeks. The biology of porcine-derived acellular dermal matrix-reinforced animals was more similar to native abdominal wall versus that with primary closure. In this study, porcine-derived acellular dermal matrix-reinforced repairs provided more complete wound healing response compared with primary closure.

Keywords: Incisional hernia; Strattice; biologic mesh; biologic tissue matrix; fascial wounds.

Figure 1.

Ultrasound image of herniated abdominal wall at 3 weeks post incision. A Toshiba Viamo ultrasound machine with a 5-MHz catheter probe was used to image hernias prior to hernia repair. Arrow indicates location of incision defect. The left abdominal rectus is present in image and is identified as the dense oblong structure to the left of the defect.

Figure 2.

Representative image of suture-only and non-cross-linked intact porcine-derived acellular dermal matrix (PADM) explants. (a) Scarring along the suture line in the muscle layer and dimpling in the abdominal wall, above and below the suture line (white arrows) in the suture-only repair group. (b) Minimum scarring was noted in the PADM-reinforced animals. Biopsy punches are designated by blue arrows.

Figure 3.

Hematoxylin and eosin staining of grafted non-cross-linked intact porcine-derived acellular dermal matrix over time. Cell infiltration (blue nuclei) and revascularization (bright eosinophilia) are notably increased over time.

Figure 4.

Hematoxylin and eosin staining of fascia tissue. Inflammation in peritoneum and fascia below the abdominal rectus was minimal for both suture-only and non-cross-linked intact porcine-derived acellular dermal matrix (PADM) groups: (a, b, e) Suture-only repair and (c, d, f) PADM reinforced. The deep red staining in (e) and (f) is indicative of calcification.

Figure 5.

Retrospective evaluation of the ultimate tensile strength of herniated versus nonherniated animals demonstrated that non-cross-linked intact porcine-derived acellular dermal matrix (PADM) remodeling of herniated versus nonherniated animals and PADM number were significantly different (ANOVA, both p < 0.0001), as determined by a general linear model with hernia formation, PADM lot, and direction of testing as model factors.  At the 4-week time point, all animals presented with a hernia post incision. The x-axis represents two groups: presence of hernia and time of euthanization following repair.  The y-axis represents the ultimate tensile strength.

Figure 6.

Within the herniated group, Young’s modulus values were statistically different between all three time points (2 and 4 weeks, 2 and 6 weeks, 4 and 6 weeks; p < 0.0001, p < 0.0001, and p < 0.021, respectively). A statistically significant increase in Young’s modulus was noted between weeks 4 and 6. The crossed circles represent the mean value of  Young’s modulus for each group. At 4 weeks, all animals presented with hernias following the 3 weeks of incision. The x-axis represents two groups: presence of hernia and time of euthanization following repair. The y-axis represents Young’s modulus.

Figure 7.

(a) Ultimate tensile stress, (b) ultimate tensile strength, and (c) Young’s modulus of the peritoneum/fascia complex at 6 weeks post hernia repair.  The crossed circles represent the mean value and the box represents 1 standard deviation from the mean. PADM: porcine-derived acellular dermal matrix.

Figure 8.

Ultimate tensile strength of the abdominal rectus muscle at 6 weeks post hernia repair.

Figure 9.

Differentially expressed genes at 2, 4, and 6 weeks in the suture-only versus non-cross-linked intact porcine-derived acellular dermal matrix (PADM) groups (>twofold, p < 0.05, 404 probes) normalized to mean expression across 24 samples compared with untreated control. Red/orange indicates high expression, yellow indicates medium expression, and blue indicates low expression. Gene expression profiles were clustered to group most similar groups together.  The untreated control and 6-week PADM repair present the most similar gene expressions.  A progression in the gene expression toward a normal untreated condition is noted in the PADM-repaired group (M) over 2, 4, and 6 weeks. In comparison, the 6-week suture-only groups (S) were least similar to the untreated control.