Mucin Covalently Bonded to Microfibers Improves the Patency of Vascular Grafts

Abstract

Due to high incidence of vascular bypass procedures, an unmet need for suitable vessel replacements exists, especially for small-diameter (<6 mm) vascular grafts. Here, we developed a novel, bilayered, synthetic vascular graft of 1-mm diameter that consisted of a microfibrous luminal layer and a nanofibrous outer layer, which was tailored to possess the same mechanical property as native arteries. We then chemically modified the scaffold with mucin, a glycoprotein lubricant on the surface of epithelial tissues, by either passive adsorption or covalent bonding using the di-amino-poly(ethylene glycol) linker to microfibers. Under static and physiological flow conditions, conjugated mucin was more stable than adsorbed mucin on the surfaces. Mucin could slightly inhibit blood clotting, and mucin coating suppressed platelet adhesion on microfibrous scaffolds. In the rat common carotid artery anastomosis model, grafts with conjugated mucin, but not adsorbed mucin, exhibited excellent patency and higher cell infiltration into the graft walls. Mucin, which can be easily obtained from autologous sources, offers a novel method for improving the hemocompatibility and surface lubrication of vascular grafts and many other implants.

Nanoparticles Complexed with Gene Vectors to Promote Proliferation of Human Vascular Endothelial Cells

“…For this purpose, hydrophilic surfaces are created by linking, e.g., polyethers or zwitter ionic moieties on the surface of the vascular graft. Examples for improving the hydrophilicity of artifi cial blood vessels include surface functionalization with poly(ethylene glycol) methacrylate (PEGMA), [ 7,8 ] poly(ethylene glycol), [ 9 ] 2-methacryloyloxyethyl phosphorylcholine, [10][11][12][13] or heparin. [ 14,15 ] Such surface modifi cations enhance the hemocompatibility, but at the same time hinder endothelial cells (ECs) to attach and cover the graft.…”

Electrospun Fibrous Architectures for Drug Delivery, Tissue Engineering and Cancer Therapy

“…Taskin et al[31c] collected the electrospun PCL fibers in dopamine solution bath to form 3D coiled PCL fiber scaffolds with in situ polymerized pDA coatings. In addition to pDA, a di‐amino‐poly (ethylene glycol) linker (di‐amino‐PEG), was also employed to act as an intermediate cross‐linker to covalently bond mucin onto the fibrous scaffolds . This conjugated mucin was more stable than simply absorbed mucin under static and flow conditions.…”

Fabrication Techniques for Vascular and Vascularized Tissue Engineering

“…For example, unmatched degradation rate with smooth muscle regeneration resulted in hyperplasia and calcification in PCL ESVGs 52a,b,61. and PLLA ESVGs without surface modification induced thrombotic occlusion53b,62…”