title: Modular Small Diameter Vascular Grafts with Bioactive Functionalities.
abstract: We report the fabrication of a novel type of artificial small diameter blood vessels, termed biomimetic tissue-engineered blood vessels (bTEBV), with a modular composition. They are composed of a hydrogel scaffold consisting of two negatively charged natural polymers, alginate and a modified chitosan, N,O-carboxymethyl chitosan (N,O-CMC). Into this biologically inert scaffold two biofunctionally active biopolymers are embedded, inorganic polyphosphate (polyP) and silica, as well as gelatin which exposes the cell recognition signal, Arg-Gly-Asp (RGD). These materials can be hardened by exposure to Ca(2+) through formation of Ca(2+) bridges between the polyanions, alginate, N,O-CMC, and polyP (alginate-Ca(2+)-N,O-CMC-polyP). The bTEBV are formed by pressing the hydrogel through an extruder into a hardening solution, containing Ca(2+). In this universal scaffold of the bTEBV biomaterial, polycations such as poly(L-Lys), poly(D-Lys) or a His/Gly-tagged RGD peptide (three RGD units) were incorporated, which promote the adhesion of endothelial cells to the vessel surface. The mechanical properties of the biopolymer material (alginate-Ca(2+)-N,O-CMC-polyP-silica) revealed a hardness (elastic modulus) of 475 kPa even after a short incubation period in CaCl2 solution. The material of the artificial vascular grafts (bTEBVs with an outer size 6 mm and 1.8 mm, and an inner diameter 4 mm and 0.8 mm, respectively) turned out to be durable in 4-week pulsatile flow experiments at an alternating pressure between 25 and 100 mbar (18.7 and 75.0 mm Hg). The burst pressure of the larger (smaller) vessels was 850 mbar (145 mbar). Incorporation of polycationic poly(L-Lys), poly(D-Lys), and especially the His/Gly-tagged RGD peptide, markedly increased the adhesion of human, umbilical vein/vascular endothelial cells, EA.HY926 cells, to the surface of the hydrogel. No significant effect of the polyP samples on the clotting of human plasma is measured. We propose that the metabolically degradable polymeric scaffold bTEBV is a promising biomaterial for future prosthetic vascular grafts.
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Meik
authors.initials: M
authors.lastname: Neufurth
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Emad
authors.initials: E
authors.lastname: Tolba
authors.affiliation: Division of Vascular Surgery, Department of Cardiothoracic and Vascular Surgery, University Medical Center of the Johannes Gutenberg University, Langenbeckstraße 1, D-55131 Mainz, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dorweiler
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Heinz C
authors.initials: HC
authors.lastname: Schröder
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Thorben
authors.initials: T
authors.lastname: Link
authors.affiliation: NanotecMARIN GmbH, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Diehl-Seifert
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Werner E G
authors.initials: WE
authors.lastname: Müller
mesh_terms: D020341:Absorbable Implants; D000464:Alginates / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry*; D001777:Blood Coagulation / Q000187:drug effects; D001807:Blood Vessel Prosthesis; D002122:Calcium Chloride / Q000494:pharmacology; D002461:Cell Line, Transformed; D048271:Chitosan / Q000737:chemistry; D055119:Elastic Modulus; D042783:Endothelial Cells / Q000166:cytology*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D008422:Materials Testing; D009842:Oligopeptides / Q000494:pharmacology*; D011122:Polyphosphates / Q000737:chemistry; D012822:Silicon Dioxide; D013718:Tensile Strength; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D058017:Vascular Grafting
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D020100:Hydrogels; D009842:Oligopeptides; D011122:Polyphosphates; C077199:O,N-carboxymethylchitosan; D012822:Silicon Dioxide; C047981:arginyl-glycyl-aspartic acid; D020723:Glucuronic Acid; D048271:Chitosan; D002122:Calcium Chloride