Search

Tissue-engineered heart valves are a promising alternative to current valve substitutes. As the main scaffold of tissue-engineered heart valves, the decellularized heart valve (DHV) has problems such as biomechanical property damage and rapid degradation. In this study, we applied a photo-crosslinking reaction induced by riboflavin and ultraviolet light A (UVA) in the DHV for improving its biomechanical properties and stability. The results showed that the biomechanical properties of the DHV significantly improved following riboflavin-UVA (R-UVA) crosslinking. Moreover, the R-UVA-crosslinked DHV (R-UV-DHV) showed better resistance to enzymatic degradation in vitro, with significantly higher thermal denaturation temperature compared to that of the untreated DHV, indicating that the stability of the R-UV-DHV improved. Histological staining and scanning electron microscopy showed that the leaflet ultrastructure was preserved better after R-UVA crosslinking compared to a glutaraldehyde-crosslinked DHV. In addition, we found that the R-UV-DHV exhibited excellent human umbilical vein endothelial cell adhesion and cells could readily grow on its surface. In an in vitro anti-calcification experiment, the R-UV-DHV demonstrated non-calcifying properties in a simulated body fluid. Furthermore, the R-UV-DHV showed characteristics of slow degradation, non-calcification, and reduced pro-inflammatory response through a rat subcutaneous implantation model. As a result, R-UVA can effectively crosslink the DHV and the R-UV-DHV possessed satisfactory biocompatibility. R-UVA crosslinking can be a new approach for improving the performance of the DHV to prepare a better scaffold for tissue-engineered valves.

Decellularized matrix is of great interest as a scaffold for the tissue engineering heart valves due to its naturally three-dimensional structure and bioactive composition. A primary challenge of tissue engineered heart valves based on decellularized matrix is to grow a physiologically appropriate cell population within the leaflet tissue. In this study, a composite scaffold was fabricated by the combination of a porous matrix metalloproteinase (MMP) degradable poly (ethylene glycol) (PEG) hydrogel that were loaded with stromal cell-derived factor-1α (SDF-1α) and a mechanically supportive decellularized porcine aortic valve. Results demonstrated that the modified scaffold enhanced bone marrow mesenchymal stem cells (BMSC) adhesion, viability and proliferation, and promoted BMSC differentiate into valve interstitial-like cells. Furthermore, these modifications lead to enhanced protection of the scaffold from thrombosis. In vivo assessment by rat subdermal model showed the modified scaffold was highly biocompatible with tissue remodeling characterized by promoting mesenchymal stem cells recruitment and facilitating M2 macrophage phenotype polarization. The surface layers of PEG hydrogel not only could provide a niche for cell migration, proliferation and differentiation, but also protect the scaffolds from rapid degeneration, inflammation and calcification. The intermediate layer of decellularized valve could maintain the organization of the scaffold and perform the valve function. The promising results emphasize the potential of our scaffolds to improve recellularization and promote remodeling of implanted decellularized valves. These findings suggest that the SDF-1α loaded MMP degradable PEG hydrogel modification could be an efficient approach to develop functional decellularized heart valve. STATEMENT OF SIGNIFICANCE: A composite scaffold was fabricated by the combination of a porous matrix metalloproteinase (MMP) degradable poly (ethylene glycol) (PEG) hydrogel that were loaded with SDF-1α and a mechanically supportive decellularized porcine aortic valve. The surface layers of PEG hydrogel not only could provide a niche for cell migration, proliferation and differentiation, but also protect the scaffolds from rapid degeneration, inflammation and calcification. The intermediate layer of decellularized valve could maintain the organization of the scaffold and perform the valve function. The promising results emphasize the ability of our scaffolds to improve recellularization and promote remodeling of implanted decellularized valves. This suggests that the extracellular matrix-based valve scaffolds have potential for clinical applications.