Technical Field
[0001]
The present invention relates to a gel material
suitable for treatment of a tendon or ligament, and a
method for treating a tendon or ligament using the gel
material.
Background Art
[0002]
In general, no effective treatment for tendon and
ligament injuries has been established to date. On the
other hand, surgical treatment, such as suture for tendon
rupture and ligament reconstruction for ligament rupture,
is the treatment of choice, while conservative treatment is
chosen for partial injuries.
[0003]
However, in both treatments, the healing process of
tendon ligament is mixed with healing by scar tissue
composed of extra-tendon cells (fibroblasts and
inflammatory cells), which inhibits healing of the tendon
or ligament itself (for example, Non Patent Literature 1).
Therefore, the strength of the cured tendon ligament
decreases to the same level as that of the scar tissue, and
2
thus the tendon cannot exert its original function. This
leads to re-rupture after surgery and hinders return to
sports, reducing the quality of life (QOL) of many
patients.
Citation List
Non Patent Literature
[0004]
Non Patent Literature 1: Best et.al, The FASEB Journal,
vol. 33, July 2019
Summary of Invention
Technical Problem
[0005]
Therefore, an object of the present invention is to
provide a method for suppressing the entry of scar tissue
in the treatment of a tendon or ligament, promoting healing
by intratendinous cells, and efficiently restoring the
original function of the tendon.
Solution to Problem
[0006]
As a result of intensive studies to solve the above
problems, the present inventors have found that coating the
area around an injured or ruptured tendon or ligament with
3
a hydrogel, which has a three-dimensional network structure
formed by intermolecular crosslinking of hydrophilic
polymers, suppresses the entry of scar tissue composed
mainly of type III collagen, and efficiently achieves
endogenous healing by intratendinous cells, thereby
completing the present invention.
[0007]
That is, in one aspect, the present invention
relates to a gel material suitable for the treatment of an
injured or ruptured tendon or ligament, and more
specifically provides the followings.
<1> A gel material including a polymer gel for
suppressing expression of type III collagen in a treatment
of an injured or ruptured tendon or ligament, in which the
polymer gel is a hydrogel having a structure in which a
hydrophilic polymer is crosslinked to form a threedimensional network structure, and has a polymer content of
from 2 to 5% by weight and an elastic modulus of from 100
to 10000 Pa.

CLAIMS
1. A gel material comprising a polymer gel for
suppressing expression of type III collagen in a treatment
of an injured or ruptured tendon or ligament,
wherein the polymer gel is a hydrogel having a
three-dimensional network structure formed by crosslinking
of hydrophilic polymers, and
wherein the polymer gel has a polymer content of
from 1 to 5% by weight and an elastic modulus of from 100
to 10000 Pa.
2. The gel material according to claim 1, wherein the
hydrophilic polymer has a polyether or polyvinyl backbone.
3. The gel material according to claim 1 or 2, wherein
the hydrophilic polymer is bi-, tri- or tetra-branched
polyethylene glycol.
4. The gel material according to any one of claims 1 to
3, wherein the hydrophilic polymer comprises a first
polymer unit having one or more nucleophilic functional
groups on a side chain or at an end and a second polymer
unit having one or more electrophilic functional groups on
a side chain or at an end.
5. The gel material according to claim 4, wherein the
nucleophilic functional group is selected from the group
consisting of a thiol group and an amino group, and the
electrophilic functional group is selected from the group
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consisting of a maleimidyl group, an N-hydroxy-succinimidyl
(NHS) group, a sulfosuccinimidyl group, a phthalimidyl
group, an imidazoyl group, an acryloyl group, a nitrophenyl
group, an isothiocyanate group, an aldehyde group, an
iodoacetamide group, a vinyl sulfone group, and -CO2PhNO2.
6. The gel material according to any one of claims 1 to
5, which is used for coating a tendon or ligament after
suture of the tendon or ligament.
7. The gel material according to claim 6, which is able
to suppress expression of type III collagen and maintain
expression of type I collagen by coating the tendon or
ligament.
8. A kit for preparing the gel material according to
any one of claims 1 to 7, which comprises two or more
solutions each containing a hydrophilic polymer.
9. A method for treating an injured or ruptured tendon
or ligament, comprising coating an area around the tendon
or ligament after suture with the gel material according to
any one of claims 1 to 7.
10. A method for suppressing expression of type III
collagen in a tendon or ligament, comprising coating an
area around the tendon or ligament after suture with the
gel material according to any one of claims 1 to 7.
11. A method for treating an injured or ruptured tendon
or ligament, comprising steps of:
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preparing a polymer solution A containing a first
hydrophilic polymer having one or more nucleophilic
functional groups on a side chain or at an end, and a
polymer solution B containing a second hydrophilic polymer
having one or more electrophilic functional groups on a
side chain or at an end;
applying the polymer solutions A and B to an area
around the tendon or ligament after suture to form a
polymer gel having a three-dimensional network structure
formed by crosslinking of hydrophilic polymers, thereby
coating the area around the tendon or ligament; and
suppressing expression of type III collagen in the
tendon or ligament by the coating.
12. The treatment method according to claim 11, wherein
the polymer gel has a polymer content of from 1 to 5% by
weight and an elastic modulus of from 100 to 10000 Pa.
13. The treatment method according to claim 11 or 12,
wherein the first and second hydrophilic polymers have a
polyether or polyvinyl backbone.
14. The treatment method according to any one of claims
11 to 13, wherein the first and second hydrophilic polymers
are bi-, tri- or tetra-branched polyethylene glycols.
15. The treatment method according to any one of claims
11 to 14, wherein the nucleophilic functional group is
selected from the group consisting of a thiol group and an
34
amino group, and the electrophilic functional group is
selected from the group consisting of a maleimidyl group,
an N-hydroxy-succinimidyl (NHS) group, a sulfosuccinimidyl
group, a phthalimidyl group, an imidazoyl group, an
acryloyl group, a nitrophenyl group, an isothiocyanate
group, an aldehyde group, an iodoacetamide group, a vinyl
sulfone group, and -CO2PhNO2.
16. A method for screening an agent effective for
treatment of an injured or ruptured tendon or ligament,
comprising a step of searching for and identifying a
compound having activity to proliferate type I collagen in
a tendon or ligament coated with the gel material according
to any one of claims 1 to 7.