Pediatric heart valve disease affects children worldwide and necessitates valve replacements that remodel and grow with the patient. Current valve manufacturing technologies struggle to create valves that facilitate native tissue remodeling for permanent replacements. Here, we present focused rotary jet spinning (FRJS) for implantable medical devices, such as heart valves, to address this challenge. Combining RJS and a focused air stream, FRJS prints FibraValves, micro- and nanofibrous heart valves, in minutes. The micro- and nanoscale features provide structural cues to orient cells at the biotic-abiotic interface, while the centimeter-scale valve shape regulates cardiac flow. We built valves using poly(L-lactide-co-Ɛ-caprolactone) fiber scaffolds, which supported rapid cellular infiltration and displayed native valve-like mechanical properties. Evaluating clinical translatability, we assessed acute performance in a large animal model using a transcatheter delivery approach. These tests indicate that FRJS is a viable method for manufacturing heart valves and future medical implants.
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This content will become publicly available on February 1, 2025
Early Feasibility Study of a Hybrid Tissue-Engineered Mitral Valve in an Ovine Model
Tissue engineering aims to overcome the current limitations of heart valves by providing a viable alternative using living tissue. Nevertheless, the valves constructed from either decellularized xenogeneic or purely biologic scaffolds are unable to withstand the hemodynamic loads, particularly in the left ventricle. To address this, we have been developing a hybrid tissue-engineered heart valve (H-TEHV) concept consisting of a nondegradable elastomeric scaffold enclosed in a valve-like living tissue constructed from autologous cells. We developed a 21 mm mitral valve scaffold for implantation in an ovine model. Smooth muscle cells/fibroblasts and endothelial cells were extracted, isolated, and expanded from the animal’s jugular vein. Next, the scaffold underwent a sequential coating with the sorted cells mixed with collagen type I. The resulting H-TEHV was then implanted into the mitral position of the same sheep through open-heart surgery. Echocardiography scans following the procedure revealed an acceptable valve performance, with no signs of regurgitation. The valve orifice area, measured by planimetry, was 2.9 cm2, the ejection fraction reached 67%, and the mean transmitral pressure gradient was measured at 8.39 mmHg. The animal successfully recovered from anesthesia and was transferred to the vivarium. Upon autopsy, the examination confirmed the integrity of the H-TEHV, with no evidence of tissue dehiscence. The preliminary results from the animal implantation suggest the feasibility of the H-TEHV.
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- Award ID(s):
- 2109959
- NSF-PAR ID:
- 10509041
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- Journal of Cardiovascular Development and Disease
- Volume:
- 11
- Issue:
- 2
- ISSN:
- 2308-3425
- Page Range / eLocation ID:
- 69
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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