Polyethylene Glycol in Medical Devices

Polyethylene glycol (PEG) is known as the best biocompatible synthetic polymer material which is colorless, odorless, with low toxicity, low immunogenicity, good water solubility and biocompatibility. It is an FDA-approved synthetic polymer with precise molecular weight, high purity, and low dispersion. In addition to being used in the long-term effect and enhancement of drugs, hydrogels made of PEG materials have also been comprehensively applied in the field of medical devices, including the adhesion, hemostasis, anti-leakage, and anti-adhesion of wounds in various surgical operations, as well as being used as raw materials for implantable medical devices, replacing existing plant, animal, or human materials.

PEG Hydrogel

Medical device products mainly use multi-arm PEG derivatives. Due to their large relative molecular weight, multi-arm PEG derivatives can form hydrogels with good water-insulating properties and tissue activity. Utilizing this property of polyethylene glycol materials, they can be made into gel-type medical devices for hemostasis and tissue isolation. Such devices can gradually degrade in the human body and be completely excreted from the body.

Fig. 1. PEG hydrogels in medical devices (Journal of Controlled Release. 2021, 330: 575-586).

Hydrogel is a kind of hydrophilic polymer cross-linked network system that fully swells in water but does not dissolve. It has the characteristics of softness, high water content, elasticity, and high biocompatibility. As a new type of soft and wet materials, hydrogels have attracted great attention in recent years in the fields of biosensing, drug delivery, tissue engineering, soft robot, etc. PEG hydrogels have the potential to prevent non-specific protein adsorption, making them one of the excellent biomaterials available for human use. In accordance with the purpose of use, hydrogels can perform different functions, such as leakage prevention, wound sealing/hemostasis, or preventing adhesion of organs. In addition, it can be used as a slow-release system, where a drug-containing hydrogel is transplanted or injected into an organism and then released into the body fluid for controlled release. PEG hydrogels have good physical and chemical properties, low toxicity, and high biocompatibility, which can be gradually degraded in the human body and completely expelled. They are used in various medical scenarios and have a broad prospect.

Polyethylene Glycols from BOC Sciences

BOC Sciences offers a range of PEG and medical device solutions that are designed to enhance the performance, safety, and efficacy of medical devices. We offer a range of surface modification technologies that can improve the biocompatibility and functionality of medical devices. These include plasma treatment, ion implantation, and chemical surface modification. BOC Sciences also offers a variety of multi-arm PEG derivatives for PEG hydrogel preparation and production.

PEG Hydrogels for Medical Devices

In 2018, the global market size for medical and pharmaceutical PEG materials was approximately $3.212 billion, according to a report by ReportsandData. It is projected to grow to $4.935 billion by 2026. The PEGylated drug market is currently in a phase of rapid development, with ongoing research further advancing the field. Currently, the application of PEG hydrogel in the field of medical devices mainly includes the following three categories:

Surgical Sealing and Hemostasis

Surgical sealing and hemostasis are among the primary applications of PEG hydrogel products, utilized in various surgical scenarios, including ophthalmic, cranial, and spinal surgeries. When PEG derivative-based hydrogels are applied to wound sites, they quickly solidify to prevent bleeding and infection, and they naturally degrade as the wound heals. Additionally, these hydrogels can be applied to organ surfaces during surgery to effectively prevent adhesions among internal organs. The excellent biocompatibility of PEG derivatives ensures that this process does not cause adverse reactions in the body; moreover, the derivatives are not absorbed but are instead metabolically excreted.

Fig. 2. CoSeal products (Source: Baxter website).

Taking Baxter's marketed product, CoSeal, as an example, its gel component consists of PEG and polyethylene. When sprayed onto tissue surfaces, it rapidly crosslinks with surface proteins, forming a mechanical bond that quickly seals vascular sutures, thereby reducing the occurrence of air leaks in pulmonary surgeries. Covidien's DuraSeal product is primarily used to seal the dura mater after sutures in neurosurgery. DuraSeal is composed of a four-armed PEG solution and a lysine solution; when these two components are mixed and sprayed onto the wound surface, the solution rapidly crosslinks into a PEG hydrogel on the tissue surface, achieving effective sealing after dura mater suturing and preventing cerebrospinal fluid leakage. This product is broken down by the body within 4 to 8 weeks. As the first dural sealant approved in the U.S. for cranial surgeries, DuraSeal not only demonstrates exceptional tissue adhesion properties but also reduces the incidence of cerebrospinal fluid leaks to only one-fourth that of traditional fibrin glue. Pre-market research showed that no leaks occurred during the evaluation period, with 98.2% of patients reaching the primary treatment endpoint and a postoperative cerebrospinal fluid leak rate of just 4.5%, clearly demonstrating the product's effectiveness. Additionally, Cardinal Health's MYNX vascular closure device series is designed with safety and patient comfort in mind, utilizing PEG polymers as sealing materials that adhere closely to the vessel wall. This allows for gentle closure of the wound without the need for clamping, suturing, or metal implants. The sealing material is fully biodegradable within 30 days after arterial healing.

Tissue Spacing in Radiation Therapy

Tissue separation in radiation therapy is an emerging application of PEG gel products. When treating cancer patients with radiation therapy, injecting PEG gel between tissues can create a barrier, effectively reducing the radiation dose that reaches surrounding healthy tissues while targeting cancer cells. SpaceOAR, produced by Augmenix, a subsidiary of Boston Scientific, was launched in 2015 as the first tissue separation product used in radiation therapy for prostate cancer in the United States. This gel is available as a water-based injection and rapidly forms a solid gel between the prostate and rectum after injection, pushing the organs apart by approximately 1.3 centimeters. The additional space created can lower the radiation dose that may affect the rectum during prostate radiation therapy, thereby reducing the risk of rectal damage. Clinical studies have shown that SpaceOAR can reduce the incidence of rectal mucosal injury in patients receiving high-dose radiation therapy from 90% to 13.6%. In a three-year follow-up, patients who received SpaceOAR before radiation therapy experienced a 73.5% reduction in late radiation toxicities or rectal injuries.

Filler Medical Devices

PEG derivatives are also utilized in the development of filler medical devices. Currently, the cross-linking agent in commercially available hyaluronic acid gels is BDDE (1,4-butanediol diglycidyl ether), which has potential carcinogenic toxicity; thus, manufacturing must limit free BDDE levels to 2 ppm. PEG derivatives, being safe and non-toxic polymers, can replace BDDE as a cross-linking agent, reducing potential toxicity risks. When cross-linked with hyaluronic acid, PEG derivatives form a larger molecular structure that retains superior support and adhesion, effectively preventing post-implant displacement. PEG hydrogels are also used to prepare absorbable, implantable drug delivery systems and to develop hydrogels with self-healing properties for treating eye diseases, antibacterial purposes, and vascular growth. Additionally, PEG hydrogels support skin wound repair in diabetes and applications in 3D cell culture.

Marketed PEGylated Medical Devices

In the international market, several PEG-modified medical device products are available, such as Covidien's DuraSeal (now transferred to Integra LifeSciences), Cardinal Health's Mynx, Boston Scientific's SpaceOAR by Augmenix, and Baxter's CoSeal. The primary PEG hydrogel-based medical devices in the European and American markets are as follows:

At present, PEG hydrogels as medical devices are extensively used worldwide. The number of PEG gel projects under development is increasing, and it is expected that their applications will be further expanded in the future. BOC Sciences can provide regulatory support for medical device companies, including assistance with FDA submissions, compliance with international standards, and product registration. Our one-stop service platform can provide the most comprehensive solution for any medical device development project applied to PEG.

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