Constructing Immunomodulator Biosynthesis Factory in Grafting-From DNA Hydrogel for Heart Valve Regeneration

Area of Science:

• Biomaterials Engineering
• Regenerative Medicine
• Immunomodulation

Background:

• Current artificial heart valves face limitations like thrombosis and calcification.
• Regenerative capabilities in heart valve prostheses are highly desirable for long-term function.
• Immune modulation is critical for successful tissue regeneration and recellularization.

Purpose of the Study:

• To develop a regenerative heart valve prosthesis with enhanced immune modulation capabilities.
• To create a 'biosynthesis factory' on decellularized heart valves (DHVs) for sustained immunomodulator production.
• To improve biocompatibility and reduce adverse reactions like calcification and adhesion.

Main Methods:

• Constructed a DNA hydrogel using rolling circle amplification (RCA) on DHVs.
• Incorporated anti-coagulation aptamers and heme oxygenase 1 (HO-1) into the DNA hydrogel.
• Crosslinked the DNA layer with zwitterionic polymers for protection and enhanced properties.

Main Results:

• The system continuously converted blood heme into immunomodulatory biliverdin.
• Achieved sustained anti-inflammatory effects and reactive oxygen species (ROS) scavenging.
• Demonstrated full endothelial cell coverage and significant extracellular matrix remodeling within one month.
• The zwitterionic polymer coating provided anti-calcification and anti-adhesion properties.

Conclusions:

• The engineered DHVs effectively create a regenerative immune microenvironment.
• This novel approach shows significant potential for developing next-generation heart valve prostheses.
• The integrated biosynthesis factory addresses key challenges in current artificial valve technology.