Modular Small Diameter Vascular Grafts with Bioactive Functionalities

• Published in: PloS one 2015-07, Vol.10 (7), p.e0133632
• Main Authors: Neufurth, Meik, Wang, Xiaohong, Tolba, Emad, Dorweiler, Bernhard, Schröder, Heinz C, Link, Thorben, Diehl-Seifert, Bärbel, Müller, Werner E G
• Format: Article
• Language: English
• Subjects: Absorbable Implants; Adhesion; Alginates - chemistry; Alginic acid; Biocompatible Materials - chemistry; Biological products; Biomaterials; Biomedical materials; Biomimetics; Biopolymers; Blood; Blood Coagulation - drug effects; Blood plasma; Blood Vessel Prosthesis; Blood vessels; Calcium alginate; Calcium chloride; Calcium Chloride - pharmacology; Cell adhesion & migration; Cell Line, Transformed; Cell recognition; Chitosan; Chitosan - chemistry; Clotting; Collagen; Elastic Modulus; Endothelial cells; Endothelial Cells - cytology; Fabrication; Gelatin; Gene expression; Glucuronic Acid - chemistry; Grafting; Grafts; Hardening; Hemodialysis; Hexuronic Acids - chemistry; Human Umbilical Vein Endothelial Cells - cytology; Humans; Hydrogels; Hydrogels - chemistry; Kinases; Materials Testing; Mechanical properties; Mercury; Modular engineering; Modulus of elasticity; Natural polymers; Oligopeptides - pharmacology; Organ transplantation; Peptides; Physiology; Polyanions; Polycations; Polyethylene terephthalate; Polymers; Polyphosphates - chemistry; Pressure; Prostheses; Prostheses and implants; Silica; Silica gel; Silicon Dioxide; Stem cells; Tensile Strength; Thrombosis; Tissue Engineering; Tissue Scaffolds; Transplants & implants; Umbilical vein; Vascular Grafting; Vascular surgery
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0133632

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.