Construction of Antithrombotic Tissue-Engineered Blood Vessel via Reduced Graphene Oxide Based Dual-Enzyme Biomimetic Cascade

Abstract

Thrombosis is one of the biggest obstacles in the clinical application of small-diameter tissue-engineered blood vessels (TEBVs). The implantation of an unmodified TEBV will lead to platelet aggregation and further activation of the coagulation cascade, in which the high concentration of adenosine diphosphate (ADP) that is released by platelets plays an important role. Inspired by the phenomenon that endothelial cells continuously generate endogenous antiplatelet substances via enzymatic reactions, we designed a reduced graphene oxide (RGO) based dual-enzyme biomimetic cascade to successively convert ADP into adenosine monophosphate (AMP) and AMP into adenosine. We used RGO as a support and bound apyrase and 5′-nucleotidase (5′-NT) on the surface of RGO through covalent bonds, and then, we modified the surface of the collagen-coated decellularized vascular matrix with the RGO-enzyme complexes, in which RGO functions as a platform with a large open surface area and minimal diffusion barriers for substrates/products to integrate two catalytic systems for cascading reactions. The experimental results demonstrate that the two enzymes can synergistically catalyze procoagulant ADP into anticoagulant AMP and adenosine successively under physiological conditions, thus reducing the concentration of ADP. AMP and adenosine can weaken or even reverse the platelet aggregation induced by ADP, thereby inhibiting thrombosis. Adenosine can also accelerate the endothelialization of TEBVs by regulating cellular energy metabolism and optimizing the microenvironment, thus ensuring the antithrombotic function and patency of TEBVs even after the RGO-enzyme complex loses its activity.

Bioinspired Soft Robots Based on the Moisture‐Responsive Graphene Oxide

“…These reveal the great potential for use in bacteria killing, [83][84][85][86] drug delivery, [87][88][89] biosensing, [90][91][92] and tissue engineering. [93][94][95] Therefore, the smart GO grippers that have antibacterial properties can be employed as a mechanical manipulator for minimally invasive surgery or organ-on-achip systems. For drug delivery applications, the GO can achieve strong interaction with anti-cancer drugs and shows sensitive response to pH value, thermal and photothermal signals, enabling large amount drug loading, controllable releasing, target delivery, and biodegradation.…”

Graphene Oxide: Opportunities and Challenges in Biomedicine

“…The incorporation of GOBMs could treat various cardiac disorders, including cardiac regeneration after myocardial infarction (MI) [ 31 , 48 ], conduction disorders, and restoration [ 31 , 46 , 48 ] Particularly in the case of MI, GOBMs can overcome the high oxidative stress in the infarcted tissue due to antioxidant activity ( Figure 3 B) [ 27 ]. A combination of other biomaterials, mostly GO and rGO, could be used for developing blood vessels [ 49 ] and heart valves [ 50 ] to overcome the malfunctions and seems to be an attractive alternative to mechanical and biological prostheses due to high durability, high biocompatibility, and being hemodynamic. Through electrospinning, random and aligned nanofibrous matrices can be fabricated to enable the investigation of isotropic conductivity [ 48 , 51 ].…”

Two-dimensional nanomaterials: fascinating materials in biomedical field

“…In addition, rGO has also been successfully tested in tissue engineering. Huo et al [84] designed rGO-enzyme-coated tissue-engineered blood vessels (TEBVs) to inhibit platelet aggregation, in which rGO functioned as a carrier to support two enzymatic catalysts, apyrase and 5-nucleotidase (5-NT) for cascading reactions (Fig. 4).…”