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Biomechanics

Biomechanics - Poster Session E

V14 - Linking Local Collagen Density to Mechanical Strength in Thoracic Aortic Aneurysms

Saturday, October 11, 2025
10:00 AM - 11:00 AM PDT
Location: Exhibit Hall F, G & H

    Presenting Author(s)

  • JB

    Janhavi M. Barpande

    Full-time Bioengineering Student
    University of Pittsburgh, United States

    • Primary Investigator(s)

  • JB

    Janhavi M. Barpande

    Full-time Bioengineering Student
    University of Pittsburgh, United States

    • Co-Author(s)

  • Pete H. Gueldner, BS

    Graduate Research Fellow
    University of Pittsburgh, United States

  • KR

    Kumbakonam Rajagopal

    University Distinguished Professor
    Texas A&M, United States

    • Last Author(s)

  • David A. Vorp, PhD

    John A. Swanson Professor of Bioengineering and the Senior Associate Dean of Research and Facilities
    University of Pittsburgh, United States


Introduction: : Aortic aneurysms involve a permanent enlargement of the aortic diameter and a loss of structural integrity of the aortic wall. Thoracic aortic aneurysms (TAAs) are the 13th most common cause of death in the United States due to dissection or rupture [1]. Dissection occurs when wall stress exceeds wall strength. It is important to understand what affects tissue strength to prevent dissection. Previously, our group treated aortic tissue homogenously with either collagenase or a sham solution to understand whether collagen contributes to tissue strength and stiffness relative to bulk material density. We found that proteolytically degrading aortic tissue lowers bulk density and overall strength of the tissue, which may give rise to TAA formation [2].

However, tissue strength can vary locally due to uneven distribution of collagen fibers. Ruddy et al examined regional heterogeneity within the aorta and found that different regions of the aorta contain varying levels of collagen contributing to differences in stiffness and greater susceptibility to aneurysm formation [3]. Areas with less collagen fiber density may be less able to withstand mechanical stress. To test this, we treated predetermined regions of aortic tissue with collagenase or sham solution. This approach allows us to study whether failure is more likely to occur in areas with reduced collagen content. We hypothesize that sections with lower collagen fiber density, induced from collagenase treatment, will fail at lower stresses during mechanical testing. If confirmed, this would suggest that the mechanical strength of aortic tissue depends primarily on local collagen fiber content.

Materials and

Methods: : Eleven thoracic pig aortas were procured from a local abattoir, then measured and cut equally into 25mm x 5mm axial sections. To administer localized treatment, a well plate was designed and 3D printed with openings through which tissue could be looped, isolating the center of the tissue from the rest and made watertight with silicone flaps (Fig. 1A). The raised section was subjected to PBS (negative control, n=5) or collagenase (n =7) treatments inside the well. The well plate was placed on top of a beaker containing PBS so that the rest of the tissue hanging below was submerged (Fig. 1A). The entire system was incubated at 37 Celsius for 24 hours. Both sham-treated and collagenase-treated samples included green food coloring in the well to mark the location of treatment on the tissue.

Each tissue sample underwent uniaxial tensile testing. The surface area of the region subjected to tension along with the green treatment region was measured between the clamps for each sample to calculate the percentage of tissue that was treated. Force-displacement data were collected continuously at 9 mm/min until failure. The location of failure (in or out of treatment location Fig. 1B), the ultimate tensile strength, and the tangent modulus in the sham-treated samples were compared to the collagenase-treated samples. 3 samples that failed at the clamps during uniaxial tensile testing were omitted from the study and not included in the sample sizes mentioned. Samples were compared using a one-tailed t-test after being tested for normality and homoskedasticity.

Results, Conclusions, and Discussions:: Collagenase-treated samples had an average treatment area of 19.49 ± 6.07 mm² (15.78% of the center surface), while sham-treated samples averaged 16.48 ± 5.91 mm² (15.37%) (p = 0.40) (Fig. 1C). Of the collagenase-treated samples, 4 out of 7 failed at the treatment location (Fig. 1B). In contrast, no failures occurred in the green-stained treatment region of any sham-treated samples (Fig. 1B), suggesting that PBS had no observable effect on local tissue strength, in contrast to the collagenase treatment. Given the treatment area represented 15% of the surface, the lack of failures in the sham group is likely due to the small sample size.

The ultimate tensile strength in collagenase-treated samples (129.41±47.33 N/cm2) was significantly lower than that of the sham-treated samples (216.92±72.98 N/cm2, p = 0.04) (Fig. 1D). The tangent modulus also decreased significantly in collagenase-treated samples (199.86±75.78 N/cm2) compared to sham-treated samples (516.12±279.31 N/cm2, p = 0.02). (Fig. 1E). A lower tangent modulus indicates reduced stiffness and increased susceptibility to deformation and tearing.

Other studies have demonstrated that collagen cross-linking enhances fiber organization and increases tissue strength [4]. While altering collagen fiber cross-linking does not directly change macro-scale collagen density, changes in fiber structure affect both local density and mechanical properties. Lee et al reported that increased cross-linking raises stiffness and reduces compliance, which can promote dissection at those sites in aneurysmal tissue [4].

In conclusion, localized collagen degradation reduces both the tissue strength and stiffness. Treated samples failed at lower stresses and more often at the treated site, supporting the idea that regions with reduced collagen content are more vulnerable to failure. Given that collagen density varies naturally along the aorta, these findings support a mechanism by which focal weaknesses contribute to aneurysm rupture.

Future work will involve testing additional porcine thoracic aortas in both the longitudinal and the circumferential orientations. Treatment location will also be varied to determine whether collagen degradation in different regions has differential effects on mechanical behavior.

Acknowledgements and/or References (Optional): : We would like to acknowledge Swanson School of Engineering for funding this project through the Summer Undergraduate Research Internship. This work is supported by the American Heart Association under Grant No. 24PRE1195123 (P.H.G.) and the National Science Foundation under Grant No. 1747452 (P.H.G.)

1. Zafar, Mohammad A., et al. “Natural history of descending thoracic and thoracoabdominal aortic aneurysms.” The Journal of Thoracic and Cardiovascular Surgery 161.2 (2021): 498-511.

2. Pete H. Gueldner, Cyrus J. Darvish, Isabelle K.M. Chickanosky, Emma E. Ahlgren, Ronald Fortunato, Timothy K. Chung, Keshava Rajagopal, Chandler C. Benjamin, Spandan Maiti, Kumbakonam R. Rajagopal, David A. Vorp, Aortic tissue stiffness and tensile strength are correlated with density changes following proteolytic treatment, Journal of Biomechanics, Volume 172, 2024

3. Ruddy, Jean Marie et al. “Regional heterogeneity within the aorta: relevance to aneurysm disease.” The Journal of thoracic and cardiovascular surgery vol. 136,5 (2008): 1123-30. doi:10.1016/j.jtcvs.2008.06.027

4. Lee, Chung Won et al. “Investigating the influence of collagen cross-linking on mechanical properties of thoracic aortic tissue.” Frontiers in bioengineering and biotechnology vol. 12 1305128. 27 Feb. 2024, doi:10.3389/fbioe.2024.1305128