(J-397) Superelastic Biodegradable Growing Percutaneous Heart Valve Frame for Pediatric Patients with Congenital Heart Valve Defects

Introduction::

Roughly one in 125 babies born in the United States have a congenital heart defect, which must be surgically repaired. Currently, heart valve replacement consists of mechanical and bioprosthetic models; however, both necessitate strenuous open-heart surgery, posing a substantial risk factor for infants [1, 2]. Recently, percutaneous heart valve replacement has been introduced with the development of novel biomaterials suggesting an innovative treatment strategy. While percutaneous heart valve replacement is an emerging technology with a few commercially available devices, the devices does not grow with a child. The need for a material to safely expand in the human body after it is successfully administered and ensure a non-toxic response from the surrounding tissue is immediate.

 

To address this issue, the use of two types of novel metallic biomaterials, i.e., superelastic nitinol and biodegradable magnesium (Mg) or iron (Fe), is proposed for developing a low-profile growing percutaneous pediatric heart valve frame. Biodegradation of either Mg or Fe will enable the pediatric device to grow with a child, while superelastic nitinol can play an important role for self-expanding mechanism.

Materials and Methods::

The study utilizes three types of primary materials: 0.055-0.120” diameter of superelastic nitinol wire, thin wall tube with inner diameter of 0.06-inch (Confluent Medical, Fremont, CA), 125mm biodegradable magnesium (Mg) wire (WE43B), 125mm pure iron (Fe) wire (GoodFellowUSA, Pittsburgh, PA).

 

Surface treatment, i.e., thermal treatment and polymer coating, has a significant impact on mechanical performance and biodegradation [3]. Thermal treatment was conducted at temperatures of 350 °C and 450 °C for .5, 1.5, and 4 hours. Additionally, Fe underwent phytic acid-metal conversion [4] and poly(carbonate urethane) urea (PCUU, inherent viscosity: 0.80±0.1) [5] coating with scanning electron microscopy (SEM) in between each coating. The Fe wires were washed in DI water, placed in a PA-Zn(N NO₃)₂ solution for 10 minutes, dried under a vacuum, dip coated, and sprayed with an airbrush. Immediately after surface treatment, four Fe wires were weighed and evaluated in an immersion test with a phosphate buffer solution (PBS) to assess their degradation for four weeks. Each week the samples were cleaned in the order of alcohol, acetone, and DI water. After the immersion test, the samples were cleaned in acetone using an ultrasonic bath and weighed.

A force measurement system (FMS-500 Starrett, Athol, MA), clipped to a Dacron strip looped around a heart valve frame, measured the radial forces to diameter reduction ratio. Computational modeling for the structural behavior study was conducted using Ansys (Ansys, Canonsburg, PA). Cell viability was quantified via Methyltransferase (MTS) assay after three days of contact with rat smooth muscle cells (rSMC).

Results, Conclusions, and Discussions::

Results
Two types of a growing heart valve frame were fabricated via computational modeling. In Figure 1(B), a low-energy laser joining method was applied in the connection regions to transfer mechanical force, e.g., torque, bending, tension and compression, to the other segments of the frame. Figure 1(C) demonstrates a 10% diameter reduction of the 15 mm Nitinol-Iron valve frame. In Figure I(D), the designed valve frames using both nitinol and iron show similar ranges of radial forces for the frames that have 10 mm to 15 mm in the deployed diameter. Figure 1(E), shows the cell viability comparison results of the thermally treated Fe wires at 1.5kW intensity of laser for 1.2 millisecond and a spot diameter of 900mm. Two different forces were applied to evaluate the relationship between the applied force and cell viability of the valve frame, i.e., 0.005N and 0.01N. The thermally treated Fe wires under 0.01N (sample #2-2) showed the highest cell viability in 3 days compared to non-treated or treated samples with lower applied force.

Discussion
Despite the advancements in endovascular devices, there are no heart valves that accommodate the anatomical changes of pediatric patients with congenital heart diseases. This new approach with superelastic nitinol and biodegradable metals demonstrates the potential of this new therapeutic option. In this approach, there are three fundamental studies which are a degradation study, a biocompatibility study, and computational modeling to assess the mechanical performance. After successfully designing a functional prototype, conducting further analysis on polymer coated Fe is crucial to gain a deeper understanding of its hemocompatibility.

Conclusion
A new heart valve frame was designed via finite element analysis (FEA) to evaluate the structural design with the radial force and percentage diameter reduction. Two prototypes with superelastic nitinol and biodegradable Fe or Mg materials have been successfully fabricated using a laser joining process and mechanical clamping process. These devices will enable the device sufficiently elastic for self-expanding percutaneous heart valves, while uniquely designed biodegradable metals will provide degradation strut portions for the growing heart valve frame.

Acknowledgements (Optional): : This research was funded by the Independent Research Award funded by the LiamWard Fund under the Children’s Heart Foundation and The University of Pittsburgh Swanson School of Engineering Summer Undergraduate Research Internship (SURI) program.

References (Optional): :

[1] A. G. Kidane et al., "Current developments and future prospects for heart valve replacement therapy," Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 88, no. 1, pp. 290-303, 2009.

[2] W. Vongpatanasin, L. D. Hillis, and R. A. Lange, "Prosthetic heart valves," New England Journal of Medicine, vol. 335, no. 6, pp. 407-416, 1996.

[3] B. A. Batista, R. B. Soares, V. d. F. C. Lins, R. B. Figueiredo, A. Hohenwarter, and T. Matencio, "Corrosion in Hank's Solution and Mechanical Strength of Ultrafine-Grained Pure Iron," Advanced Engineering Materials, vol. 22, no. 7, p. 2000183, 2020.

[4] R. Yan et al., "A simple and convenient method to fabricate new types of phytic acid–metal conversion coatings with excellent anti-corrosion performance on the iron substrate," RSC advances, vol. 7, no. 65, pp. 41152-41162, 2017.

[5] X. Gu et al., "Biodegradable, elastomeric coatings with controlled anti-proliferative agent release for magnesium-based cardiovascular stents," Colloids and Surfaces B: Biointerfaces, vol. 144, pp. 170-179, 2016.