Multilayer vascular grafts based on collagen-mimetic proteins

Area of Science:

• Biomaterials Science
• Vascular Tissue Engineering
• Regenerative Medicine

Background:

• Developing off-the-shelf small-caliber vascular grafts faces challenges with endothelialization, thrombosis, intimal hyperplasia, and mechanical integrity.
• Existing synthetic grafts often lack bioactivity, leading to poor integration and adverse healing responses.
• Achieving rapid endothelial cell coverage while preventing blood clotting is crucial for graft success.

Purpose of the Study:

• To evaluate a novel multilayered vascular graft design combining a bioactive poly(ethylene glycol) (PEG)-Scl2 hydrogel with an electrospun polyurethane mesh.
• To assess the biomechanical properties, stability, bioactivity, hemocompatibility, and endothelial cell response of the composite graft.
• To determine the potential of this design as an improved off-the-shelf vascular graft alternative.

Main Methods:

• Conjugation of a collagen-mimetic protein (Scl2) to a PEG hydrogel to create a bioactive, thromboresistant surface.
• Reinforcement of the PEG-Scl2 hydrogel with an electrospun polyurethane mesh to achieve desired mechanical properties.
• Evaluation of composite burst pressure, compliance, suture retention, stability after drying/sterilization, endothelial cell adhesion/spreading, platelet interactions, and endothelial cell migration speed.

Main Results:

• The composite graft achieved biomechanical properties comparable to saphenous vein autografts and demonstrated stability after drying, sterilization, and pulsatile flow conditioning.
• Scl2 bioactivity was retained post-processing, supporting endothelial cell adhesion and spreading.
• The PEG-Scl2 hydrogel exhibited minimal platelet adhesion and activation, indicating thromboresistance.
• Endothelial cell migration speed on PEG-Scl2 hydrogels was higher than on PEG-collagen analogs and tunable by protein concentration.

Conclusions:

• The multilayered PEG-Scl2/polyurethane composite graft demonstrates promising bioactivity, hemocompatibility, and mechanical integrity for vascular tissue engineering.
• This design addresses key limitations of current synthetic grafts and warrants further investigation as a potential off-the-shelf solution.
• The ability to tune endothelial cell migration via protein concentration offers a method for optimizing graft healing.