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Bioactive 3D-Printed valve scaffold promoting valvular regeneration via immunomodulation and endothelialization
Kun Yang1, Xianzhen Dong2, Linlin Guo3
1National Engineering Research Center for Nanomedicine, Research Center for Intelligent Fiber Devices and Equipment, State Key Laboratory of New Textile Materials and Advanced Processing, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
Engineered heart valve scaffolds with a layered, bioactive design reduce blood clot formation and inflammation. This approach promotes healing and endothelialization, improving tissue-engineered valve performance.
Area of Science:
- Biomaterials Engineering
- Regenerative Medicine
- Cardiovascular Research
Background:
- Tissue-engineered heart valves face challenges like thrombosis, inflammation, and poor endothelialization at the blood-material interface, limiting their in vivo performance.
- Existing scaffolds often lack integrated biological cues to actively manage the immune response and promote healing.
Purpose of the Study:
- To engineer a bioinstructive, multilayered heart valve scaffold addressing key interfacial barriers.
- To integrate structural and biological functions for improved hemocompatibility and regenerative potential.
Main Methods:
- Fabrication of a 3D-printed framework with silk fibroin wrapping and a hydrogel biointerface.
- Incorporation of Arg-Gly-Asp/GelMA adhesive cues and hydrogen sulfide (H2S)-releasing microgels.
- In vitro assessment of endothelial cell behavior and macrophage phenotype, alongside in vivo evaluation of scaffold performance.
Main Results:
- The scaffold demonstrated valve-relevant mechanical properties and promoted endothelial cell migration, proliferation, and angiogenesis.
- Sustained H2S release shifted macrophages to a pro-resolving M2-like phenotype, reducing inflammation.
- In vivo studies showed mitigation of thromboinflammatory reactions, preliminary anti-calcification effects, and successful endothelialization.
Conclusions:
- A layered, bioactive engineering strategy transforms passive scaffolds into regenerative, hemocompatible, and immunoregulatory heart valve constructs.
- This approach offers a promising design principle for developing advanced regenerative valve scaffolds.
- The engineered scaffold successfully addresses critical blood-material interface challenges for improved in vivo performance.
