Bioprinted Tri-leaflet Scaffold for Aortic Heart Valve Function and Repair
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De Jesus, Kenneth J.
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Abstract
Heart valve disease (HVD) is a prevalent and increasing clinical burden, with limited treatment options typically restricted to valvular repair or prosthetic replacement surgery. Existing alternatives, such as biological and mechanical valve replacements, have been recognized as inadequate for proper function in pediatric patients. The inability of these valves to grow or biologically respond to their environment presents ongoing challenges, often necessitating multiple valve-refitting surgeries and lifelong anticoagulation dependency. To this end, tissue- engineered heart valves (TEHVs) have emerged as an attractive therapeutic solution, offering patient-specific models that can self-repair and remodel. Advances in 3D bioprinting enable the recreation of native heterogeneity and anatomical fidelity, facilitating customizable designs. The proposed study focuses on constructing a TEHV using 3D bioprinting to recreate the three-layer leaflet structure of an aortic valve composed of poly-e-caprolactone (PCL) and a cell-laden gelatin- methacrylate (GelMA) and polyethylene glycol diacrylate (PEGDA) hydrogel scaffold, incorporating valvular interstitial- like (VIC-like) cells to promote regeneration and remodeling. The study is composed of two specific aims: (1) developing and assessing the feasibility of a 3D bioprinted, multilayered scaffold that emulates native valve structures and (2) evaluating the remodeling capabilities of the scaffold and extracellular matrix (ECM) production under dynamic bioreactor conditions to optimize valve performance. This project aims to describe the cellular and mechanical interactions between biomaterials and cells to overcome risks in pediatric populations, integrating autologous stem cells, biomaterials, and 3D bioprinted scaffolds to generate a valve leaflet capable of biological integration and mechanical function for optimal restoration.
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2024-12-02
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Dissertation (PhD)