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 Ca2+ through formation of Ca2+ bridges between the polyanions, alginate, N,O-CMC, and polyP (alginate-Ca2+-N,O-CMC-polyP). The bTEBV are formed by pressing the hydrogel through an extruder into a hardening solution, containing Ca2+. 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-Ca2+-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.

Amorphous polyphosphate, a smart bioinspired nano-/bio-material for bone and cartilage regeneration: towards a new paradigm in tissue engineering

“…64 A growth of studies occurred after the introduction of the technology to fabricate Ca-polyP microparticles. 71 Subsequently, those particles had been included in scaffolds, microspheres or pastes for the application in skin, 234 teeth, 235 artificial blood vessels 236 and for wound healing. 237 In addition, due to the beneficial hardening characteristics as an implant material, a further momentum was reached, with respect to implant fabrications also in a personalized way, as well as a potential help in osteoporosis.…”

Bioprinting for vascular and vascularized tissue biofabrication

“…These failures are usually due to initimal hyperplasia, thrombosis or infections of the graft. Absence of healthy endothelial cell layer, diameter mismatch, synthetic material surface properties and compliance mismatch with the native tissue are contributory factors to all these mechanisms [36,37]. Bioprinting with suitable endothelial cell source into the diameters required is thus an attractive approach to engineer small diameter blood vessels and has been pursued.…”

3D Bioprinting Strategies for the Regeneration of Functional Tubular Tissues and Organs

“…Blood vessels are divided into arteries, veins, and capillaries according to their structural characteristic and biological functions. In general, the artery and vein walls consist of three layers: tunica intima (squamous endothelium), tunica media (smooth muscle cells), and tunica adventitia (fibrous collagen) [132,133].…”