Leaflet Tissue Generation from Microfibrous Heart Valve Leaflet Scaffolds with Native Characteristics

Abstract

Mechanical and bioprosthetic valves that are currently applied for replacing diseased heart valves are not fully efficient. Heart valve tissue engineering may solve the issues faced by the prosthetic valves in heart valve replacement. The leaflets of native heart valves have a trilayered structure with layer-specific orientations; thus, it is imperative to develop functional leaflet tissue constructs with a native trilayered, oriented structure. Its key solution is to develop leaflet scaffolds with a native morphology and structure. In this study, microfibrous leaflet scaffolds with a native trilayered and oriented structure were developed in an electrospinning system. The scaffolds were implanted for 3 months in rats subcutaneously to study the scaffold efficiencies in generating functional tissue-engineered leaflet constructs. These in vivo tissue-engineered leaflet constructs had a trilayered, oriented structure similar to native leaflets. The tensile properties of constructs indicated that they were able to endure the hydrodynamic load of the native heart valve. Collagen, glycosaminoglycans, and elastinthe predominant extracellular matrix components of native leafletswere found sufficiently in the leaflet tissue constructs. The residing cells in the leaflet tissue constructs showed vimentin and α-smooth muscle actin expression, i.e., the constructs were in a growing state. Thus, the trilayered, oriented fibrous leaflet scaffolds produced in this study could be useful to develop heart valve scaffolds for successful heart valve replacements.

Elastomeric Trilayer Substrates with Native-like Mechanical Properties for Heart Valve Leaflet Tissue Engineering

“…Cell and ECM morphology and orientation are impacted by the orientation of the fibers in electrospun substrates . Also, substrates with native-like anisotropy and mechanical properties could enhance cell proliferation and ECM production. , Thus, the PCL and PCL/PLCL cell-cultured constructs were stained with H&E, Masson’s trichrome, or Alcian blue to confirm the presence and orientation of cells, collagen fibrils, and GAG, respectively.…”

“…In both constructs, most collagen fibrils were in the circumferential layer, and few were in the middle or radial layers, similar to the ECM composition of native leaflets. 62 Further, the higher mechanical properties of the circumferential layers of the constructs could have increased collagen fibril growth in that layer. 66 Alcian blue-stained PCL constructs showed significant GAG production in the circumferential layer (Figure 7i−j).…”

“…In healthy native tissue, VICs have a quiescent fibroblast phenotype characterized by moderate levels of vimentin (VIM) and low levels of α-smooth muscle actin (α-SMA). 62 Upon exposure to non-native stresses (e.g., high non-native mechanical properties, tissue damage, etc. ), the fibroblasts become activated, transdifferentiate into myofibroblasts, and express high levels of VIM and α-SMA.…”

“…This observation indicated that more PVICs were in a growth state in the PCL/PLCL constructs, possibly because of the native-like properties of the substrates. 14,62 Among the three layers, the circumferential and radial layers showed the highest vimentin expression. This result could be due to the aligned fibers in these layers causing the PVICs to have an aligned morphology and produce more vimentin to maintain their elongated shape.…”

Cardiovascular Tissue Engineering and Regeneration: A Plead for Further Knowledge Convergence

“…An additional aspect that comes with differentiation is the reinvention of technologies across the areas. As examples, one could refer to the design of layered scaffolds for vessels that were reinvented for heart valves, 9,10 or the design of strut-based, biofunctionalization stents, reinvented for vascular scaffolds to accelerate, for example, in vivo endothelialization. 11,12 Acknowledged reinvention is ideal if the application is successful, but disastrous if failures in one area are ignorantly copied to another.…”