Biomimetic polymeric transcatheter heart valve leaflets with low calcification and good regenerative ability.
Xiaoxiao WangHonghui JiangWenjie ZhangYuanyuan KongDeling KongJing LiuZhihong WangPublished in: Journal of materials chemistry. B (2023)
Transcatheter aortic valve replacement (TAVR) technology is quickly advancing in clinic, however, as it expands to low-risk populations and younger patients (age <65 years), device durability is becoming a major challenge. Tissue-engineered heart valves (TEHVs) are a potential alternative. In this study, a bionic tri-layer tissue-engineered heart valve was constructed using poly (L-lactate- co -ε-caprolactone) (PLCL), gelatin (GEL), hyaluronic acid (HA) and silk fibroin (SF), to simulate the fibrosa, spongiosa and ventricular layer of natural heart valves. To obtain a scaffold with sufficient strength and regenerative capacity, we optimized the ratio of components of each layer. The physical and mechanical properties were tested, and the cytocompatibility, calcification deposition and regeneration potential were tested in a rat model of subcutaneous implantation. Finally, the hydrodynamic function of the new TAVR device was verified. The results demonstrated that the strength of the tri-layer valve could reach up to 10 MPa, significantly higher than that of the PLCL and mono-layer groups. Most importantly, calcification related gene expression was down-regulated in the TEHV groups compared to valvular interstitial cells (VICs) treated with calcification induced medium, and calcification levels of TEHVs in in vivo assay were below 0.5 μg mg -1 . Besides, we found HA in the middle layer was very conducive to rapid cell infiltration and good angiogenesis, which ultimately promoted host tissue regeneration at 8 weeks after implantation. Collectively, we provide a bionic tri-layer electrospun leaflet with appropriate mechanical strength, low calcification and good regenerative capacity, which has great potential as a TEHV leaflet.
Keyphrases
- aortic valve
- transcatheter aortic valve replacement
- tissue engineering
- aortic stenosis
- stem cells
- chronic kidney disease
- aortic valve replacement
- transcatheter aortic valve implantation
- hyaluronic acid
- end stage renal disease
- mitral valve
- heart failure
- gene expression
- cell therapy
- ejection fraction
- wound healing
- mesenchymal stem cells
- atrial fibrillation
- dna methylation
- high throughput
- newly diagnosed
- climate change
- mental health
- endothelial cells
- primary care
- risk assessment
- transcription factor
- left ventricular
- cell cycle arrest
- cell death
- single cell
- preterm birth
- endoplasmic reticulum stress
- sensitive detection
- high glucose
- physical activity
- prognostic factors