Development of an Innovative Surgical Suture Material That Prevents the Formation of Arterial Thrombosis

INTRODUCTION

The number of reconstructive operations on various vascular basins is increasing every year in Russia and the world, and in particular, there is a significant increase in arterial reconstructions on the lower extremities [1, 2]. The most common complication of these operations is vascular prosthesis thrombosis – up to 45% [3]. Suture materials in vascular surgery have special requirements. One of the most important requirements is the absence of thread penetration into the lumen of the vessel and its contact with flowing blood [4, 5], however, it is almost impossible to avoid this. In this case, a violation of the integrity of the patient's artery endothelium site in the suture area and the presence of a thread protruding into the lumen of the vessel turn the anastomosis zone into a focus of thrombosis, which is a serious problem in vascular surgery [6-8]. Currently, the suture materials market is represented by various modifications, for example, filaments with antibacterial or anti-inflammatory effects [9-14]. At the same time, there is no suture material with thromboresistant properties in the arsenal of vascular surgeons.

Arterial and venous thrombosis are serious postoperative complications [15, 16]. Approximately 4% of surgical operations are accompanied by the development of venous or arterial thrombosis [17, 18]. There are some factors associated with these complications: atherosclerosis of the coronary arteries in elderly patients, male gender, and a history of venous thromboembolism [19-21]. At the same time, there is a small amount of data indicating the relationship between postoperative thrombosis and infection.

Systemic infections accompanied by inflammation and hypercoagulation may increase the subsequent risk of thrombosis [22, 23]. Moreover, prolonged inflammation is associated with an increased risk of myocardial infarction and stroke, as well as deep vein thrombosis and pulmonary embolism [24-27]. It is assumed that hypercoagulation indirectly develops through platelet activation, increased production of fibrin and tissue factors [28-30].

The purpose of this scientific work is to evaluate the possibility of modifying the surface of a polypropylene thread with heparin using chemical inoculation in order to increase the thromboresistant properties of the suture material.

MATERIALS AND METHODS

In this work, a 3/0 thick polypropylene thread was used. polyhydroxybutyrate/oxivalerate (PHBV) copolymer with a molecular weight of 280 kDa and a solution (0.5%) of unfractionated heparin were used to coat the surface of the thread. For the strong grafting of heparin to the polymer, an additional sublayer of polymethacrylyl chloride was used, chemically grafted to the polymer filament and having active groups in its composition that can react and form strong covalent bonds with heparin. Methacrylyl chloride (methacrylic acid chlorangidride) was used to create it. Purified benzoyl peroxide (BP) or dinitrile azo-bis-isobutyric acid (DAA) was introduced into the modifying solution of PHBV as the initiator of vaccination, in an amount of 2% of the weight of PHBV. Methacrylyl chloride was grafted to PHBV from the gas phase when heated. Inoculation of heparin on the modified surface was carried out from its solution in a bicarbonate buffer at a reduced temperature. After inoculation, the filaments were washed with distilled water and dried in a vacuum over P₂O₅ at room temperature for 2 days.

The inoculation of heparin to the substrate was studied by diffuse scattering spectroscopy using an IR Fourier spectrometer Bruker Vertex 80v (Germany). To increase the area of the test surface of the samples, the modified thread was tightly wound onto a two-layer plate made of thick aluminum foil with dimensions of 0.5x2.0 cm so that a completely closed thread section with dimensions of 0.5x0.5 cm was formed.

The quality of the applied coating was evaluated using scanning electron microscopy (SEM) on a Hitachi-S3400N microscope (Japan).

RESULTS AND DISCUSSION

The scientific literature has long described the technologies of radiation-chemical inoculation of heparin to the surface of various polymers in order to increase their hemocompatibility [31-34]. To do this, the polymer substrate was modified by grafted copolymerization with methacrylyl chloride, which subsequently reacted with heparin to form strong covalent ester bonds. However, the radiation method used for this with the help of gamma radiation is technically difficult, unsafe, and unsuitable for large-scale production. The most promising method is the chemical initiation of grafted copolymerization of methacrylyl chloride [35].

Inoculation of the active sublayer, which has active chlorohydride groups in its composition, was carried out by radical inoculation in the presence of initiators (BP or DAA). When heated, these compounds decompose into active radical particles (Figure 1), which react with the polymer matrix (PHBV), dehydrating it to form macroradicals (Figure 2). Subsequently, the macroradicals react with methacrylyl chloride to form a grafted copolymer.

The polymer substrate modified by grafted copolymerization with methacrylyl chloride subsequently reacted with heparin to form strong covalent ester bonds (Figure 3).

The inoculation of heparin to the substrate was studied using the diffuse infrared spectroscopy method, which is widely used to study the surface of various objects [36, 37]. This method allows us to obtain reliable information about changes in the composition of the sample surface without adversely affecting it. As can be seen from the above spectrum (Figure 4), a number of differences are observed between the suture material modified with heparin and the original polypropylene thread coated with PHBV, namely:

• an increase in absorption in the region of 3400–3000 cm^-1, which is associated with the appearance of a large number of hydroxyl groups of grafted heparin;
• in addition to the general peak at 1740-1720 cm^–1 (the characteristic peak of the carboxylic ester group of PHBV), new peaks appear at 1696 cm^-1 - absorption of acid carboxylic groups – COOH of heparin and polymethacrylic acid bound by a hydrogen bond, and a peak at 1637 cm^-1 – absorption of the carboxylate group – COO^- heparin and polymethacrylic acid.

These differences confirm the inoculation of heparin to the polymer surface. At the same time, both initiators – dinitrile azobisisobutyric acid and benzoyl peroxide – are approximately equivalent in their properties in the inoculation copolymerization reaction.