PEG Hydrogels in Medical Devices

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PEG Hydrogels in Medical Devices

Polyethylene glycol (PEG) is nontoxic, non-immunogenic, non-antigenic,
highly soluble in water and FDA approved. Besides being widely used for
long-lasting and potentiation of drugs, hydrogels made of PEG materials are
also widely used in the field of medical devices, including adhesion,
hemostasis, anti-leakage and anti-adhesion of wounds in various surgical
procedures, and as raw materials for implantable medical devices, replacing
existing materials of plant, animal or human origin.

Hydrogels are hydrophilic, three dimensional cross-linked polymer
systems that can swell in water and hold a large amount of water while
maintaining the structure. As a novel material, hydrogels have attracted much
attention in recent years for applications in biosensing, drug delivery, tissue
engineering, soft robotics, etc.

With the potential to integrate biophysical and biochemical cues to prevent
non-specific protein adsorption, PEG hydrogels are one of the excellent
biomaterials that can be used in the human body. With good
physicochemical properties, low toxicity and high biocompatibility, PEG
hydrogels can be gradually degraded in the human body and completely
excreted out of the body, which can be widely used in various biomedical
applications. PEG hydrogels are used extensively in the controlled release of
therapeutics, in medical devices, and regenerative medicine, and in various
other applications, including wound sealing and healing, 3D printing of
biosimilar materials, or as cartilage replacement.

Currently, there are several PEG-modified medical device products on the
market, such as Covidien's DuraSeal, Cardinal Health's Mynx, Augmenix's
SpaceOAR and Baxter's CoSeal. The major PEG hydrogel-based medical
device products available in Europe and the United States are listed below.

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Table1. Approved medical devices based on PEG hydrogels

Tissue Adhesives for Hemostasis and Wound Healing

Tissue adhesives for hemostasis and wound healing is one of the main
applications of PEG hydrogel products. The hydrogel, which is mainly
composed of PEG derivatives, can be sprayed onto the wound surface and
cured rapidly to prevent wound bleeding and infection, and degrade by itself
after the wound heals. At the same time, PEG-based hydrogel can effectively
prevent the adhesion of internal organs during surgery when sprayed onto the
surface of organs. Due to the good biocompatibility of PEG derivatives, this
process does not cause abnormal reactions in the human body. The PEG
derivatives are not absorbed by the body and can be metabolized out of the
body.

COSEAL is composed of two biocompatible PEG derivatives that combine with
dilute hydrogen chloride solution to rapidly form a covalently bonded hydrogel
and adhere to both tissue and synthetic graft materials, which can provide a
rapid seal at vascular suture lines, as well as reduce air leaks occurring after
lung resection.

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Figure 1. COSEAL Surgical Sealant, source: Baxter official website

DuraSeal® is a self-polymerizing agent which rapidly forms a firm, watertight
hydrogel layer within several seconds of application over the dural surface.
DuraSeal consists of a 4-arm PEG solution and a trilysine amine solution. After
spraying on the trauma surface, the two components can be rapidly
cross-linked into PEG hydrogel on the surface of human tissue to achieve the
effect of sealing the dura mater after suturing and preventing the leakage of
cerebrospinal fluid, after which it is decomposed by the human body within 4~8
weeks.

Figure 2. DuraSeal® Dural Sealant System, source: Integralife official website

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As the first dural sealant approved for craniofacial surgery in the United States,
DuraSeal not only has excellent tissue adhesion properties, but also has a
post-operative cerebrospinal fluid leak rate that is only 1/4 of that of traditional
fibrin glue. Pre-market studies showed no leaks during the evaluation period,
98.2% of patients met the primary treatment endpoint, and the incidence of
post-operative cerebrospinal fluid leakage was only 4.5%, demonstrating the
effectiveness of the product.

Cardinal Health's MYNX CONTROL™ Vascular Closure Device, designed with
safety and patient comfort in mind, uses PEG polymer as the sealing material
against the vessel wall to gently close the wound without clamping, suturing or
the use of a metal implant, and the sealing material completely degrades after
the artery heals within 30 days.

Protective Barrier in Radiation Therapy

When treating cancer patients with radiation therapy, PEG hydrogel can be
injected to create space between tissues, thus protecting the healthy tissue
from the high dose radiation needed to treat the cancer cells.
SpaceOAR Hydrogel is a semi-solid, natural substance that radiation
oncologists use to decrease toxicity to the nearby rectum from radiation beams
targeting the prostate. By acting as a spacer, the SpaceOAR hydrogel
temporarily moves the rectum a half inch (1.3 cm) away from the prostate, thus
helping to reduce the radiation dose delivered to the rectum and may eliminate
or decrease damage. Clinical studies have shown that SpaceOAR reduces
rectal mucosal injury from 90% to 13.6% in patients receiving high-dose
radiation therapy. At a three-year follow-up, patients who received SpaceOAR
prior to radiotherapy experienced 73.5% less late radiation toxicity or rectal
injury.

Figure 3. SpaceOAR Hydrogel, Source: SpaceOAR official website

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Dermal Fillers for Esthetic Applications

Hyaluronic acid (HA) based hydrogels for esthetic applications found
widespread use. HA hydrogel crosslinked with PEG has been recently
introduced. The existing commercially available HA hydrogels are all applied
with the crosslinker BDDE (1,4-butanediol diglycidyl ether), which requires the
free BDDE content to be controlled at 2 ppm in the production process due to
its potential carcinogenic toxicity. In contrast, the use of PEG derivatives as
crosslinkers instead of BDDE can reduce the potential toxicity risk of the
product, due to the nontoxicity of PEG derivatives. Meanwhile, PEG
derivatives cross-linked with HA can form a macromolecule with a more
three-dimensional spatial structure, which can maintain excellent support for a
long time and show stronger adhesion, effectively preventing displacement
after implantation.

In addition, PEG hydrogels can be used to prepare absorbable implantable
drug delivery systems and have also been used to develop self-healing ligand
hydrogel injections for the treatment of eye diseases, antibacterial and
angiogenesis, skin wound healing due to diabetes and 3D cell culture.
Huateng Pharma's multi-arm PEG derivatives can be cross-linked
into hydrogels, with high purity and low polydispersity.Huateng Pharma offers
milligram to kilogram scale manufacture of multi-arm PEG derivatives in both
GMP and non-GMP grades for your needs, such
as 4-ArmPEG-SS, 4-ArmPEG-SG, 8-ArmPEG-SS and 8-ArmPEG-SG, etc.

References:
[1] Hutanu, D., et al., Recent Applications of Polyethylene Glycols (PEGs) and PEG
Derivatives. Mod Chem appl, 2014, 2(132).
[2] Enrica Caló, Vitaliy V. Khutoryanskiy, Biomedical applications of hydrogels: A review of
patents and commercial products, European Polymer Journal, Volume 65, 2015, Pages
252-267, ISSN 0014-3057, https://doi.org/10.1016/j.eurpolymj.2014.11.024.