Novel Hydrogel Material as a Potential Embolic Agent in Embolization Treatments

Abstract

We report a novel graphene-oxide (GO) enhanced polymer hydrogel (GPH) as a promising embolic agent capable of treating cerebrovascular diseases and malignant tumors, using the trans-catheter arterial embolization (TAE) technique. Simply composed of GO and generation five poly(amidoamine) dendrimers (PAMAM-5), our rheology experiments reveal that GPH exhibits satisfactory mechanical strength, which resist the high pressures of blood flow. Subcutaneous experiments on Sprague-Dawley (SD) rats demonstrate the qualified biocompatibility of GPH. Finally, our in vivo experiments on New Zealand rabbits, which mix GPH with the X-ray absorbing contrast agent, Iohexol, reveal complete embolization of the artery. We also note that GPH shortens embolization time and exhibits low toxicity in follow-up experiments. Altogether, our study demonstrates that GPH has many advantages over the currently used embolic agents and has potential applications in clinical practice.

Figure 1. Schematic diagram showing the formation of GPH2.

Figure 2

(a) The comparison of changes of the storage modulus and loss modulus (15 min after the addition of GDL) of GPH2 with other GPH samples. (b) Strain dependent storage modulus, loss modulus, and compressive modulus for GPH2.

Figure 3

(a) HE staining microscopy images of GPH2 four weeks after subcutaneous injection. A small amount of inflammatory response is shown around the graphene oxide. (b) CLSM images of GPH2 four weeks after subcutaneous injection. The inset shows the clear border of the tissues and GPH2. (c) SEM images of GPH2 compounds in vivo after subcutaneous injection for four weeks. (d) SEM image of pure GPH2.

Figure 4

(a–d) Screen capture of DSA embolization. (a) Before embolization, the contrast agent can pass the subclavian artery. (b) GPH was injected smoothly into the target artery. The red arrow points to the micro catheter’s mouth. (c) After embolization, the contrast agent cannot infuse the distal segment of the subclavian artery. It turns back at the embolization site. (d) Two weeks later, the contrast agent still stops at the embolization site (the red arrow indicates the end of the artery stops at the collarbone and no artery can be seen under the collarbone). The contrast agent can pass the right subclavian artery smoothly (white arrow; under the collarbone).

Figure 5

(a) HE staining image of GPH2 after DSA embolization. The artery is completely blocked. (b) CLSM image of GPH2 after embolization. (c) HE staining microscopy image of left paw tissue after embolization. No inflammation and fragments of GPH can be seen. (d) CLSM image of left paw tissue after DSA embolization.

Figure 6

(a,b) HE staining images of liver tissue. (c,d) HE staining images of kidney tissue. (e,f) HE staining images of lung tissue.