Dynamic stiffness enables stage-specific properties mediating functional endothelialization on vascular implants

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cardiovascular Engineering

Background:

• Achieving functional endothelialization in cardiovascular implants is crucial for neointima healing.
• Current strategies struggle with dynamic material-tissue interactions.
• Developing adaptive biomaterials is essential for improving vascular implant outcomes.

Purpose of the Study:

• To develop a biomimetic coating with dynamic stiffness for enhanced vascular implant healing.
• To investigate the coating's ability to mimic the extracellular matrix (ECM) and respond to microenvironmental cues.
• To evaluate the coating's efficacy in promoting endothelialization and suppressing neointimal hyperplasia in vivo.

Main Methods:

• Layer-by-layer assembly of collagen and hyaluronic acid derivatives to create a dynamic stiffness coating.
• Postcrosslinking to stabilize the coating structure.
• In vitro assessment of coating properties, including stiffness modulation in response to stimuli (glutathione, reactive oxygen species) and cell interactions.
• In vivo evaluation of coated stents in a relevant animal model to assess neointimal hyperplasia and healing at 12 months.

Main Results:

• The biomimetic coating exhibited tunable stiffness that decreased in response to microenvironmental stimuli.
• The coating demonstrated stage-specific biological responses, including suppression of thrombosis, promotion of endothelial monolayer formation, induction of smooth muscle cell contractile phenotype, and anti-inflammatory macrophage polarization.
• In vivo studies showed that coated stents significantly suppressed neointimal hyperplasia.
• Vascular implants achieved neointimal healing with morphology and function similar to native endothelium after 12 months.

Conclusions:

• Dynamic stiffness is a critical factor in guiding material-tissue responses for improved vascular implant healing.
• The developed biomimetic coating offers a promising strategy to enhance endothelialization and achieve functional neointima healing in cardiovascular implants.
• This approach provides a novel method for designing adaptive biomaterials to better integrate with host tissues.