Modular Small Diameter Vascular Grafts with Bioactive Functionalities

PLoS One. 2015 Jul 23;10(7):e0133632. doi: 10.1371/journal.pone.0133632. eCollection 2015.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants*
  • Alginates / chemistry
  • Biocompatible Materials / chemistry*
  • Blood Coagulation / drug effects
  • Blood Vessel Prosthesis*
  • Calcium Chloride / pharmacology
  • Cell Line, Transformed
  • Chitosan / chemistry
  • Elastic Modulus
  • Endothelial Cells / cytology*
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Human Umbilical Vein Endothelial Cells / cytology
  • Humans
  • Hydrogels / chemistry
  • Materials Testing
  • Oligopeptides / pharmacology*
  • Polyphosphates / chemistry
  • Silicon Dioxide
  • Tensile Strength
  • Tissue Engineering
  • Tissue Scaffolds
  • Vascular Grafting

Substances

  • Alginates
  • Biocompatible Materials
  • Hexuronic Acids
  • Hydrogels
  • Oligopeptides
  • Polyphosphates
  • O,N-carboxymethylchitosan
  • Silicon Dioxide
  • arginyl-glycyl-aspartic acid
  • Glucuronic Acid
  • Chitosan
  • Calcium Chloride

Grants and funding

NanotecMARIN GmbH provided support in the form of salaries for the author BDS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. WEGM is a holder of a European Research Council (ERC) Advanced Investigator Grant (“BIOSILICA”: No. 268476) and the ERC-PoC Grant (“MorphoVES-PoC”: No. 662486). This work was supported by grants from the Deutsche Forschungsgemeinschaft (Schr 277/10-3), the European Commission (“Bio-Scaffolds”: No. 604036 and “BlueGenics”: No. 311848), and the International Human Frontier Science Program.