Functional living trileaflet heart valves grown in vitro

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cardiovascular Engineering

Background:

• Traditional tissue engineering for heart valves faces challenges with structural immaturity and suboptimal mechanical properties.
• Autologous tissue-derived valves offer potential for improved integration and reduced immunogenicity.

Purpose of the Study:

• To develop implantable, mature heart valves using autologous tissue within a biomimetic in vitro environment.
• To assess the in vivo performance and structural integrity of these engineered valves.

Main Methods:

• Fabrication of trileaflet heart valves using bioabsorbable polymers seeded with autologous ovine myofibroblasts and endothelial cells.
• Cultivation in a pulse duplicator system for 14 days under dynamic flow and pressure conditions.
• In vivo implantation into lambs, followed by explantation at various time points for analysis.

Main Results:

• Engineered valves demonstrated successful integration and function in lambs for up to 20 weeks, with no stenosis or thrombus.
• Histology revealed mature, layered cuspal tissue with confluent endothelium and mechanical properties comparable to native tissue.
• Complete polymer degradation by 8 weeks, with increased extracellular matrix and DNA content mirroring native valve tissue.

Conclusions:

• In vitro generation of complete, living heart valves is feasible using a biomimetic flow culture system.
• Autologous tissue-engineered valves exhibited successful function, microstructure, and matrix formation in vivo for up to 5 months.