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When medical devices (such as pacemakers) or materials are implanted in the body, they usually trigger the body's foreign body reaction, causing proteins to adsorb on the surface of the device and recruit immune cells such as macrophages and neutrophils to gather on the surface of the material.

The aggregation of fibrotic cells to achieve collagen deposition easily forms fibrosis, causing the device to be excessively surrounded by fibrotic tissue to form a physical barrier, thereby causing the material to lose the ability to exchange information with tissues or release signal factors.

Although methods based on chemically modifying the device surface or loading anti-inflammatory drugs can reduce the formation of fibrosis to a certain extent, they cannot completely suppress this phenomenon in the long term.

Recently, Professor Xuanhe Zhao and Dr. Jingjing Wu of the Massachusetts Institute of Technology discovered for the first time a non-fibrotic adhesive material that can bond medical implants to surrounding tissues to prevent fibrosis after implantation. This is like putting an "invisible cloak" on the device, blocking attacks from the immune system and thereby extending the service life of such devices.

Figure 丨 Adhesive coating prevents the formation of fibrous capsules at the implant-tissue interface (Source: Nature)

This study inhibits fibrosis formation by using hydrogel adhesives, which is expected to provide solutions for the clinical application of more medical devices implanted in the body for long-term work. For example, it can protect medical devices such as long-term drug delivery, cell delivery, and sensor delivery in the body to provide long-term treatment or diagnosis functions.

Professor David Mooney of Harvard University, a member of the American Academy of Sciences, commented on the study: "Strong adhesion between medical devices and tissues can avoid the formation of fibrotic tissue. This is an important discovery with many potential applications in the field of medical devices."

Recently, a related paper titled “Adhesive anti-fibrotic interfaces on diverse organs” was published in Nature[1].

Dr. Jingjing Wu of MIT is the first author, and Professor Xuanhe Zhao and Dr. Hyunwoo Yuk are co-corresponding authors.

Figure 丨 Related papers (Source: Nature)

Previously, in studies on the use of adhesive materials to repair soft tissue organ defects in special environments, researchers found that adhesive materials can quickly repair defective tissues and promote wound healing [2-3].

In this study, non-fibrotic adhesives were introduced to reduce the adsorption of nonspecific proteins (such as albumin and fibrinogen) in the body, thereby reducing the infiltration of a large number of inflammatory cells.

After studying immune proteins and genomics, the researchers found that only a small number of inflammatory regulatory factors increased within 3 days, but all inflammatory factors decreased significantly after 7 days.

Wu Jingjing explained: "This is mainly due to the fact that a small number of neutrophils gathered near non-fibrotic adhesion agents. Within 1-3 days, the expression of the nos2 gene increased significantly, activating the neutrophil-mediated inflammatory response and causing a large amount of secretion of inflammatory factors G-CSF and IL-12p70."

Photo: Wu Jingjing (Source: Wu Jingjing)

Due to the body's own regulation, inflammatory factors can quickly subside within 7 days, thus interrupting the subsequent fibrosis process. Non-fibrotic adhesives are used as coatings. When medical devices are implanted in the body, they no longer produce fibrosis, providing a guarantee for long-term existence and operation in the body.

In the initial stage of the research, the research team implanted adhesives into tissue organs during the experiment. Although it was observed that adhesives could inhibit the formation of fibrosis, there was no in-depth understanding of the immune mechanism behind this abnormal phenomenon at that time.

Figure 丨 Quantitative polymerase chain reaction and Luminex analysis of adhesive implant interface (Source: Nature)

To explore the immunological mechanism behind this phenomenon, the team and its collaborators used a series of biological characterization methods, including immunofluorescence, quantitative polymerase chain reaction, transcriptome sequencing technology, etc., to analyze the immunological mechanism behind this phenomenon.

The researchers also compared multiple control groups and found a phenomenon: if the group material and tissue adhere closely, the memory of inflammatory cells will be reduced. If the same material does not have the property of adhesion, inflammatory cells can still penetrate between the material and tissue, leading to an inflammatory response and the formation of fibrosis.

Wu Jingjing said: "We found that immune cells such as neutrophils first began to infiltrate the implanted area, but the immune attack was soon curbed, blocking the process of fibrotic tissue formation. No fibrosis occurred within three months of implantation, and the long-term transmission of electrical signals was still maintained."

Non-fibrotic adhesives are polymers composed of macromolecules such as chitosan or polyvinyl alcohol. They have the advantages of wide sources, low prices and high softness, and are very compatible with the mechanical properties of human tissues.

This research solves the problem of fibrosis caused by foreign body reactions caused by implanted materials in the body, which has plagued mankind for a long time, making it possible for medical devices or materials to work in the body for a long time.

At present, the team has verified its ability to inhibit fibrosis through experiments in animal models of mice, rats, humanized mice and pigs, such as the abdominal wall, stomach, colon, heart and lungs, so non-fibrous adhesives show broad application prospects.

Based on this discovery, the research team subsequently developed a temporary pacemaker[4]. Wu Jingjing has verified that the adhesive applied to the pacemaker can continue to work in the body when implanted in animals (rats).

In addition, it can electrically stimulate the heart and provide stable electrophysiological signal monitoring and regulation, which is expected to be used to treat clinical problems such as arrhythmia/myocardial infarction.

Figure 丨 Continuous cardiac monitoring and pacing in rat models (Source: Science Translational Medicine)

Nature commented on the study[5], stating that the main highlight of the study was the ability of the adhesive coating to reduce the formation of scar tissue around soft polymer implants – an effect the authors demonstrated in a number of animal models in which the biomaterials were implanted in or on various organs.

The formation of scar tissue around implanted biomaterials is a common problem that can affect their function, and the researchers have demonstrated promising progress in addressing this important issue.

Wu Jingjing said: "We hope to achieve technology transformation as soon as possible and promote its clinical human trials. But this requires strict technical and ethical approval, which is expected to be completed in the next two to three years."

References:

1.Wu, J., Deng, J., Theocharidis, G. et al. Adhesive anti-fibrotic interfaces on diverse organs. Nature (2024). https://doi.org/10.1038/s41586-024-07426-9

2.Wu, J. et al. An off-the-shelf bioadhesive patch for sutureless repair of gastrointestinal defects. Science Translational Medicine 14, abh2857(2022). https://doi.org/10.1126/scitranslmed.abh2857

3.Yuk, H., Wu, J., Sarrafian, T.L. et al. Rapid and coagulation-independent haemostatic sealing by a paste inspired by barnacle glue. Nature Biomedical Medicine 5, 1131–1142 (2021). https://doi.org/10.1038/s41551-021-00769-y

4.Deng,Y., Wu,J. et al. A bioadhesive pacing lead for atraumatic cardiac monitoring and stimulation in rodent and porcine models. Science Translational Medicine 16，eado9003(2024). https://doi.org/10.1126/scitranslmed.ado9003

5.https://www.nature.com/articles/d41586-024-02348-y

Operation/Layout: He Chenlong

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