[POSTECH, Ewha Womans University, and Catholic Medical University joint research team develops a light-crosslinkable bioadhesive hydrogel based on mussel adhesive protein for nerve regeneration.]

[Sutureless neurorrhaphy amplifies nerve regeneration effect.]

A technology that can connect severed nerves without surgical sutures has been developed. This technology employs a mussel adhesive protein and has recently drawn attention since it not only reduces the time burden of the medical staff but also prevents secondary damage to patients that might occur using the suture method.

A research team led by Professor Hyung Joon Cha and Dr. Hogyun Cheong (Department of Chemical Engineering) from POSTECH has developed an innovative hydrogel medical adhesive based on mussel adhesive protein in collaboration with Professor Kye Il Joo (Division of Chemical Engineering and Materials Science, Ewha Womans University), Professor Young-Joon Jun and Professor Jong Won Rhie (Department of Plastic Surgery and Reconstructive Surgery at Seoul St. Mary’s Hospital of the Catholic University of Korea), and Professor Jong In Lee (Department of Rehabilitation Medicine at Seoul St. Mary’s Hospital of the Catholic University of Korea).

The findings from this study, which has opened new possibilities for sutureless neurotherapy using bio-inspired adhesive materials, has recently been published in Chemical Engineering Journal, the most prestigious international academic journal in chemical engineering.

The regeneration of nerve tissue is difficult, and the only treatment in case of accidental severing or neurotmesis has been elaborate neurorrhaphy^*1 using sutures. However, this method requires highly skilled medical staff and takes a lengthy procedure. Furthermore, it can hinder nerve regeneration due to the secondary damage inflicted by penetrations during suturing.

The joint research team attempted to overcome this challenge by creating a photo-crosslinkable bioadhesive hydrogel using mussel adhesive protein with the functional peptide Substance-P (SP), a tachykinin-family neurotransmitter. This adhesive hydrogel, which exists in a liquid state at first, instantly transforms into a hydrogel state and gains adhesive properties when exposed to blue light.

Sutureless neurorrhaphy using this bioadhesive hydrogel with functional peptide Substance-P not only prevents secondary nerve damage but also polarizes macrophages^*2 into the M2 subtype thereby decreasing the additional inflammatory responses of the affected area. Accordingly, nerve regeneration is also effectively promoted.

As a result of the study, a nerve tissue regeneration effect similar or superior to that of the conventional suture anastomosis was verified in the direct neurorrhaphy of severed nerves model as well as gap neurorrhaphy of a 1.2-cm nerve loss model. Particularly, even in the case of 1.2-cm nerve loss model, the prognosis of sutureless neurorraphy, in terms of both motor and sensory functions of regenerated nerve, were superior to that of suture anastomosis.

Professor Hyung Joon Cha of POSTECH remarked, “We have opened the possibility of dramatically reducing the operating time for medical staff and enhancing the prognosis for patient using a harmless medical adhesive for nerve regeneration based on a mussel adhesive protein, an innovative source material.” He added, “We will spur the development of various innovative medical adhesives that can be applied for surgeries of affected areas other than nerves.”

The study was conducted with the support from the Ministry of Oceans and Fisheries’ Marine Biotechnology Program and the Korea Health Technology R&D Project funded by the Ministry of Health and Welfare of Korea.

Meanwhile, the technology transfer of the mussel adhesive protein material to Nature Gluetech Co., Ltd. has been completed. Among these, “FIxLight,” a light cross-linked medical adhesive for soft tissue, such as epidermis and etc., is undergoing clinical trials after the approval of investigational new drug application (IND).

DOI: https://doi.org/10.1016/j.cej.2022.136641

1. Neurorrhaphy
A surgical procedure that connects severed or damaged nerves, and so far, the only treatment method for severed nerves is suturing.

2. Macrophage
A cell distributed throughout the body and responsible for immune function that can be polarized into many subtypes, among which, polarization from the immune-inducing M1 subtype to the immune-suppressing M2 subtype facilitates nerve regeneration.