(G-258) Durability Assessment of Unseeded Porcine Intestinal Submucosa Scaffold as a control prior to seeding with stem cells

Introduction:: Infants with critical heart valve defects face high mortality rates and limited treatment options. Porcine small intestine submucosa (PSIS) valves have been used in the compassionate care of children with critical congenital heart valve disease. Nevertheless, it has limited success due to a hostile immune response, as the PSIS valve leaflets are not fully filled by regenerated tissues in the host. To tackle this issue, our lab is working to improve this problem by seeding PSIS with stem cells, cultured under dynamic oscillatory flow, to promote faster tissue growth, in the host, and thereby avoiding a hostile immune response. Specifically, this process results in an allogenic elastin-rich layer that can accelerate heart valve regeneration by recruiting cells that can then increase complete extracellular matrix formation. The allogenic elastin is retained after removing all the stem cells by decellularization. To mechanically compare these elastin-rich engineered valves to unseeded PSIS, the durability of raw PSIS scaffolds was assessed by evaluating a 3-month enlargement/stretching via SEM imaging with the Elastin Rich layered valves.


Materials and Methods:: The Cormatrix PSIS Bio-scaffolds underwent accelerated wear testing using the HiCycle Durability Tester from the Vivitro Labs Corp. The tests were conducted in 0.9% saline water at a frequency of 275 beats per minute (BPM) to simulate a three-month period. An average of 1.2 beats per second was calculated over a 24-day testing period. The tests were conducted at 37°C with a pressure amplitude ranging from 80 mmHg to 120 mmHg and a 0.5 offset. To evaluate any changes in the fiber orientation, scanning electron microscopy (SEM) was used to assess any defects on the leaflets and covered surfaces.


Results, Conclusions, and Discussions:: During wear testing, SEM analysis showed that the fiber composition was more consistent in areas covered by the valve holder (Figure 1A). However, the leaflets showed some delamination (Figure 1B). In this experiment, comparing the PSIS valves with the optimized, dehydrated, decellularized, and allogeneic Elastin-rich engineered valves are expected to yield wear characteristics similar to those of our control group. Consequently, analogous testing will be conducted over the same time frame to verify consistent functionality and performance. Note that our lab has already conducted raw PSIS valve assessment in the juvenile baboon animal model, which demonstrated that in vivo, the raw PSIS valves functions for a minimum of 3 months. Hence, the primary objective of this in vitro durability assessment is to ensure that the allogeneic Elastin-rich engineered valves are at minimum identical to the raw PSIS valves. This will serve as a robust model for subsequent investigations and applications before returning to juvenile baboon in vivo assessments next, with our allogeneic Elastin-rich engineered valves.


Acknowledgements (Optional): : We hereby acknowledge the Miami Heart Research Institute for funding this project.

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