Mitigation of diabetes-related complications in implanted collagen and elastin scaffolds using matrix-binding polyphenol

Abstract

There is a major need for scaffold-based tissue engineered vascular grafts and heart valves with long-term patency and durability to be used in diabetic cardiovascular patients. We hypothesized that diabetes, by virtue of glycoxidation reactions, can directly crosslink implanted scaffolds, drastically altering their properties. In order to investigate the fate of tissue engineered scaffolds in diabetic conditions, we prepared valvular collagen scaffolds and arterial elastin scaffolds by decellularization and implanted them subdermally in diabetic rats. Both types of scaffolds exhibited significant levels of advanced glycation end products (AGEs), chemical crosslinking and stiffening - alterations which are not favorable for cardiovascular tissue engineering. Pre-implantation treatment of collagen and elastin scaffolds with penta-galloyl glucose (PGG), an antioxidant and matrix-binding polyphenol, chemically stabilized the scaffolds, reduced their enzymatic degradation, and protected them from diabetes-related complications by reduction of scaffold-bound AGE levels. PGG-treated scaffolds resisted diabetes-induced crosslinking and stiffening, were protected from calcification, and exhibited controlled remodeling in vivo, thereby supporting future use of diabetes-resistant scaffolds for cardiovascular tissue engineering in patients with diabetes.

J-shaped stress-strain diagram of collagen fibers: Frame tension of triangulated surfaces with fixed boundaries

“…3. From the snapshots, we confirm that the variable σ is locally ordered when H/H 0 = 1 for κ = 1 while it is globally J-shaped stress and strain diagram [1][2][3][4]. The canonical model is defined as…”

“…The mechanical properties of macroscopic membranes, such as human skin, have been extensively studied experimentally for a long time [1][2][3]. One interesting mechanical property is the stress-strain diagram.…”

Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System

“…32,33 Square-shaped samples of cca. 8 · 8 mm were dissected from the aortic valve cusps, sinuses, and aorta tissues of each group.…”

“…Immunohistochemistry (IHC) was performed for type IV collagen as described previously 32 in the Leica Bond Max automated IHC system (Leica Microsystems, Inc.) using a rabbit anti-human type IV collagen antibody (Abcam ab6586, cross reacts with pig antigen) at 1:250 dilution (4 mg/mL). Slides were incubated with primary antibody for 15 min.…”

Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

“…Valve-derived scaffolds are preferred because of easy accessibility, outstanding hemodynamic properties and the preservation of biological "niches" after decellularization (10)(11)(12). We also treat acellular scaffolds with penta-galloyl glucose (PGG) for tissue stabilization, to prevent premature scaffold degradation and to reduce calcification (13)(14)(15). We chose ADSCs because they are easy to obtain in large numbers and because of their plasticity and ability to differentiate into valve cells (7,16).…”