In situ endothelialization of intravascular stents coated with an anti-CD34 antibody functionalized heparin-collagen multilayer.
The in-stent restenosis (ISR) and the late stent thrombosis (LAST) represent the most common failures of stent implantation and are both mediated at the injured endothelium. The natural endothelium healing mechanism provides an approach to achieve in situ endothelialization of the implant by stimulating the neighboring endothelial cells (ECs) migration or capturing the circulating endothelial cells (CEC) directly from the blood circulation. An anti-CD34 antibody functionalized multilayer of heparin/collagen is developed here via layer-by-layer assemble. The ellipsometry and QCM-D results demonstrate that the multilayer coatings with slight glutaraldehyde cross-linking are stable in static incubation and flushing conditions, respectively. The in vitro hemocompatibility tests and cell culture results indicate that both heparin/collagen multilayers with or without the anti-CD34 antibody functionalization not only preserve good hemocompatibility, but also promote cell attachment and growth notably. While the heparin/collagen multilayer coatings show no selectivity in promotion of ECs and smooth muscle cells (SMCs), the anti-CD34 antibody functionalized heparin/collagen multilayers can specifically promote the attachment and growth of the vascular ECs. The metabolic activity assessment and the NO secretion measurements further indicate that the adherent ECs on the anti-CD34 antibody functionalized heparin/collagen multilayer surface have better viability and possess the specific function of the natural vascular ECs. In vivo experiments indicate that the anti-CD34 antibody can enrich and accelerate the attachment of the vascular cells onto the stent and rapid endothelialization is realized. While no significant difference of neointimal hyperplasia is observed between the bare metal stents and heparin/collagen multilayer modified stents, the neointimal hyperplasia on the anti-CD34 antibody functionalized multilayer modified stents is significantly inhibited. The success of the anti-CD34 antibody functionalized heparin/collagen multilayer coating in rapid endothelialization and anti-restenosis might indicate that the immobilization of ECs specific ligand onto a cytocompatible matrix can be a good approach for in situ endothelialization and a possible solution to ISR.
Lin
Quankui
Q
Department of Polymer Science and Engineering, Key Laboratory of Macromolecule Synthesis and Functionalization of the Ministry of Education, Zhejiang University, Hangzhou, China.
Ding
Xin
X
Qiu
Fuyu
F
Song
Xiaoxiao
X
Fu
Guosheng
G
Ji
Jian
J
D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D018952:Antigens, CD34 / Q000276:immunology; D001807:Blood Vessel Prosthesis; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004727:Endothelium / Q000378:metabolism*; D005263:Femoral Artery / Q000187:drug effects / Q000473:pathology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D055767:Immobilized Proteins / Q000494:pharmacology; D008422:Materials Testing; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D011817:Rabbits; D015607:Stents
D000906:Antibodies; D018952:Antigens, CD34; D020099:Coated Materials, Biocompatible; D055767:Immobilized Proteins; D006493:Heparin; D003094:Collagen