Stabilized Collagen and Elastin-Based Scaffolds for Mitral Valve Tissue Engineering

Abstract

There is a significant clinical need for new approaches to treatment of mitral valve disease. The aim of this study was to develop a tissue-engineered mitral valve scaffold possessing appropriate composition and structure to ensure ideal characteristics of mitral valves, such as large orifice, rapid opening and closure, maintenance of mitral annulus-papillary muscle continuity, in vivo biocompatibility and extended durability. An extracellular matrix-based scaffold was generated, based on the native porcine mitral valve as starting material and a technique for porcine cell removal without causing damage to the matrix components. To stabilize these structures and slow down their degradation, acellular scaffolds were treated with penta-galloyl glucose (PGG), a well-characterized polyphenol with high affinity for collagen and elastin. Biaxial mechanical testing presented similar characteristics for the PGG-treated scaffolds compared to fresh tissues. The extracellular matrix components, crucial for maintaining the valve shape and function, were well preserved in leaflets, and in chordae, as shown by their resistance to collagenase and elastin. When extracted with strong detergents, the PGG-treated scaffolds released a reduced amount of soluble matrix peptides, compared to untreated scaffolds; this correlated with diminished activation of fibroblasts seeded on scaffolds treated with PGG. Cell-seeded scaffolds conditioned for 5 weeks in a valve bioreactor showed good cell viability. Finally, rat subdermal implantation studies showed that PGG-treated mitral valve scaffolds were biocompatible, nonimmunogenic, noninflammatory, and noncalcifying. In conclusion, a biocompatible mitral valve scaffold was developed, which preserved the biochemical composition and structural integrity of the valve, essential for its highly dynamic mechanical demands, and its biologic durability.

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics

“…The application of PGG to native tissue (other than scaffolds) has been limited to the pericardium 168 and heart valves 167 for development of bioprosthetics only. PGG treated tissues exhibited excellent biaxial mechanical behavior, 39,154,170 tear resistance, 47,168,171 and diametrical compliance. However, it is important to note that most of this cross-linking makes the resulting tissue stiffer compared to the native one (e.g., TRI formation of PGG 167 ).…”

“…70,88 The aforementioned advantages of PGG have paved the path for its use in tissue engineering studies of valves, development of vascular grafts, and numerous other potential therapeutic applications. 32,33,35,39,47,88,119,120,129,154,156,167,168,170,171 In this review, we critically evaluate recent work relevant to drug-delivery and translation-related applications of PGG.…”

“…One of the envisioned roles of PGG in arterial stability would be the ability to deposit and/or preserve elastin lamellae, 32,33,35,39,70,119,120,124,129,156,177 which is essential for the prolonged functioning of blood vessels and maintaining their biomechanical integrity. Sinha et al .…”

“…This stabilized form of structural proteins has a direct effect on the mechanical behavior of PGG treated tissues. 33,35,39,47,108,129,154,167,168,170,172,177 As most studies have utilized a pathological condition (e.g., AAA) or tissue-engineering based approach, PGG treatment has been focused on degenerated ECM tissues 70,88,119,120,156 and decellularized tissue constructs, 32,33,35,47,129,154,170,171 respectively. The application of PGG to native tissue (other than scaffolds) has been limited to the pericardium 168 and heart valves 167 for development of bioprosthetics only.…”

Human Adipose-Derived Hydrogel Characterization Based on In Vitro ASC Biocompatibility and Differentiation

“…Gelatin Zymography. MMP-2 and MMP-9 activities were analyzed by gelatin zymography using a modification of the methods described previously [29,43,44]. ASC-seeded hydrogels (n = 3) were cultured in stromal, adipogenic, and osteogenic media for 14 or 28 days.…”