Collagen Matrix Remodeling in Stented Pulmonary Arteries after Transapical Heart Valve Replacement

Abstract

The use of valved stents for minimally invasive replacement of semilunar heart valves is expected to change the extracellular matrix and mechanical function of the native artery and may thus impair long-term functionality of the implant. Here we investigate the impact of the stent on matrix remodeling of the pulmonary artery in a sheep model, focusing on matrix composition and collagen (re)orientation of the host tissue. Ovine native pulmonary arteries were harvested 8 (n = 2), 16 (n = 4) and 24 (n = 2) weeks after transapical implantation of self-expandable stented heart valves. Second harmonic generation (SHG) microscopy was used to assess the collagen (re)orientation of fresh tissue samples. The collagen and elastin content was quantified using biochemical assays. SHG microscopy revealed regional differences in collagen organization in all explants. In the adventitial layer of the arterial wall far distal to the stent (considered as the control tissue), we observed wavy collagen fibers oriented in the circumferential direction. These circumferential fibers were more straightened in the adventitial layer located behind the stent. On the luminal side of the wall behind the stent, collagen fibers were aligned along the stent struts and randomly oriented between the struts. Immediately distal to the stent, however, fibers on both the luminal and the adventitial side of the wall were oriented in the axial direction, demonstrating the stent impact on the collagen structure of surrounding arterial tissues. Collagen orientation patterns did not change with implantation time, and biochemical analyses showed no changes in the trend of collagen and elastin content with implantation time or location of the vascular wall. We hypothesize that the collagen fibers on the adventitial side of the arterial wall and behind the stent straighten in response to the arterial stretch caused by oversizing of the stent. However, the collagen organization on the luminal side suggests that stent-induced remodeling is dominated by contact guidance.

In Vivo Collagen Remodeling in the Vascular Wall of Decellularized Stented Tissue-Engineered Heart Valves

“…The final published version may differ from this proof. 16 16 HYP in 24 weeks explants was higher compared to the native pulmonary artery located behind the stent as shown in a previous study [25].…”

“…Fibers were aligned in the direction of the stent struts next to the struts and aligned randomly inbetween the struts. In a previous study, we showed the same pattern at the luminal side of the stented pulmonary artery, where the tissue was touched by the stent [25]. However, it was shown that collagen fibers remained circumferentially aligned in the outer region of the pulmonary artery, where the tissue was not in direct contact with the stent.…”

Evaluation of an elastic decellularized tendon‐derived scaffold for the vascular tissue engineering application

“…Moreover, they have been used as a template for the cells to synthesize their ECM in a desired direction, preferably identical to their native counterparts. Since topological features provided by the scaffold direct the orientation of both the cells and the synthesized ECM, it is important to use a scaffold with appropriate alignment to produce constructs with initial native‐like anisotropic structure …”

Special Issue: Spotlight on the Future of Cardiovascular Engineering:Frontiers and Challenges in Cardiovascular Biomechanics

“…Similarly, Wang et al used SHG to image collagen fiber uncrimping and rotation during inflation of carotid arteries [24]. SHG has also been used to image extracellular matrix (ECM) changes during G&R, including cardiac fibrosis following pressure overload [25] and collagen fiber remodeling in stented pulmonary arteries [26]. Pursell et al used SHG in this special issue to relate structural changes in collagen fibers to mechanical changes in the pulmonary artery with induced hypertension [6].…”