JP7333553B2 - Method for manufacturing soft tissue adhesive material, method for manufacturing implantable sensor, method for manufacturing soft tissue deformation aid, method for manufacturing soft tissue perforation sealing material, and method for manufacturing soft tissue reinforcing material - Google Patents

Description

The present invention relates to a method for manufacturing an adhesive material for soft tissue, a method for manufacturing an implantable sensor, a method for manufacturing a soft tissue deformation aid, a method for manufacturing a soft tissue perforation sealing material, and a method for manufacturing a soft tissue reinforcing material.

When living tissue is destroyed by external invasion such as injury or surgery, it is necessary to restore its shape. At present, it is common to use sutures made of silk or bioabsorbable polymers for this tissue reconstruction. On the other hand, a biological tissue adhesive may be used as an emergency measure. Currently, fibrin glue, cyanoacrylate-based adhesives, etc. are used as the biological tissue adhesives.

On the other hand, in recent years, the development of chips to be implanted in the body has been actively promoted. Implanted chips are used, for example, to monitor physical, chemical, and biological environmental changes within the body. For this purpose, the implanted chip needs to be retained in a certain place in the body for a long period of time, but the present situation is that there is no adhesive that achieves such chip retention in the body for a long period of time.

Titanium is widely used as an implant material in the fields of dentistry and orthopedics as a metal material with high biocompatibility. Past uses include dental implants, artificial hip joints, bone fixation plates and screws, and meshes for retaining bone grafts. Titanium becomes titanium oxide due to passivation on the surface immediately after processing. It is known that when this titanium oxide surface is implanted in the bone for a long period of time such as 4 weeks, it directly joins with the bone (osseointegration), but it shows instant adhesiveness to the living soft tissue within a few seconds. do not have.

Japanese Patent Application Publication No. 2018-521720

Rupp F, 4 others, "Surface characteristics of dental implants: A review", Dental Materials, 2018, Vol.34, p.40-57 Luigi Canullo, et al., "Soft tissue cell adhesion to titanium abutments after different cleaning procedures: Preliminary results of a randomized clinical trial," Med Oral Pathol Oral Cir Bucal., March 1, 2014, Vol. 19, No. 2. No., e177-e183

By the way, body tissue adhesion using a suture thread is an effective method for the purpose of suturing body tissues. However, success of suturing often depends on an individual's technique, and shortening of the time is desired. In addition, in order to connect a non-soft material such as a sensor made of metal or glass to a living tissue using a suture, it is necessary to add various shapes to the hard material, such as making holes in advance.

The fibrin glue and cyanoacrylate adhesive mentioned above are now widely used in Japan as adhesives for living tissue. However, although fibrin glue has excellent biocompatibility, it has low adhesive strength, and cyanoacrylate adhesive has excellent adhesive strength but has low biocompatibility. In addition, cyanoacrylate adhesives may cause poor curing when there is a lot of moisture, or the tissue may be broken due to external force due to excessive adhesive strength, and when necessary, it may be difficult to remove. There is also the problem of difficulty.

In addition, since the biological tissue adhesive is used as a liquid, there is a problem that it tends to move to a site that does not require adhesion or to adhere to a site that does not require adhesion. Furthermore, there is a problem that the operability is inferior because the operation can be performed only during the time until the liquid is polymerized and solidified, and the operation time is limited.

A lot of research has been done so far on implanting titanium materials in vivo, but most of them look at bonding and bonding with hard tissues, and do not aim at bonding with soft tissues (Non-Patent Literature 1). Currently, most of the papers on bonding with soft tissue indicate that bonding with soft tissue occurs after protein adsorption and subsequent adhesion of cells (see Non-Patent Document 2), and within a few seconds There have been no reports on events such as adhesion of tissues to each other or adhesion to living tissues. In other words, "adhesion of tissues" and "adhesion of cells to substrates" have different meanings even though they use the same word "adhesion". The data described in Non-Patent Document 2 are obtained by evaluating a state in which a dental implant abutment is in contact with soft tissue for one week. Moreover, since cell adhesion generally requires 6 hours or longer, soft tissue adhesion described in Non-Patent Document 2 requires at least 12 hours or longer.

Patent Document 1 discloses that the surface of a body made of titanium or a titanium alloy is etched with a first etchant containing a mineral acid, and then etched with an etchant containing hydrofluoric acid. or to provide a surface of a dental implant abutment intended to be brought into contact with bone tissue or soft tissue, respectively, during use. However, the technique described in Patent Document 1 also aims at bonding the implant and the bone over a long period of time such as four weeks (see paragraph 0142 of Patent Document 1).

SUMMARY OF THE INVENTION The present invention has been made in view of such circumstances, and an object of the present invention is to enable a solid member to be easily adhered to living soft tissue in a short period of time. Together, we propose various useful applications of this adhesion. In addition, the solid member having the ability to adhere to the soft tissue of a living body as described above is called an "adhesive material" to distinguish it from an amorphous adhesive.

One aspect of the present invention for achieving the above objects is acid treatment, alkali treatment, and alkaline acid treatment (in this specification, treatment in which acid treatment is performed after alkali treatment is abbreviated as "alkaline acid treatment ”) by performing any one of the chemical treatments to form an uneven structure of nano to micrometer size on the surface of the titanium material, and by bringing the surface of the titanium material into contact with the biological soft tissue, the titanium material and the above A method for adhering a titanium material and a soft living tissue, characterized by adhering the soft living tissue.

In this method, at least part of the surface of the titanium material is chemically treated to form an uneven structure of nano to micrometer size, more specifically, ten nanometers to several micrometers on that portion. , the surface of the titanium material can be endowed with adhesiveness with soft biological tissue. Here, by using thin film-like or foil-like titanium (hereinafter referred to as titanium thin film), it becomes possible to deform the titanium thin film according to the deformation of soft soft tissues. In order to provide such deformability, it is preferable that the thickness of the titanium thin film is thin, and specifically, a thickness of several hundred nanometers to 100 micrometers is preferable.

In addition, the above chemical treatment is any one of acid treatment, alkali treatment, and alkaline acid treatment.In any case, the surface of the titanium material dissolves, and the dissolved titanium ions react with the solute. Precipitation is thought to form the uneven structure. The titanium material imparted with adhesiveness can be adhered to the soft living tissue by applying a slight force and bringing it into contact with the soft living tissue. In preferred embodiments, this adhesion can be achieved with as little contact as 1-30 seconds.

The titanium material before chemical treatment is not only pure titanium, but also pure titanium containing some impurities and additives to the extent that the adhesiveness to the soft tissue of the body after chemical treatment is not lost. An alloy containing an element other than titanium may be used. Alloys other than titanium, such as titanium-aluminum-vanadium alloy, titanium-aluminum-molybdenum-vanadium alloy, titanium-aluminum-tin-zirconium-molybdenum alloy, nickel-titanium alloy, titanium-niobium alloy, titanium-niobium-tantalum -Molybdenum alloys and titanium-gold-chromium-tantalum alloys.

In addition, if the titanium material and the soft biological tissue are bonded on both sides so as to sandwich the thin film or plate-like titanium material, a plurality of soft biological tissues or a plurality of divided soft biological tissues can be connected to each other via the titanium material. can be glued to Therefore, the method for bonding the titanium material and the soft biological tissue described above can also be used as a method for bonding the soft biological tissue using the titanium material.

Also, in the bonding method, the chemical treatment may include an acid treatment with a hydrochloric acid solution, a nitric acid solution, a sulfuric acid solution, a hydrogen peroxide solution, hydrofluoric acid, hydrobromic acid, or a mixture thereof. In particular, it may include acid treatment by immersing the titanium material in an acid solution, which may be a hydrochloric acid solution, a sulfuric acid solution , or a mixture thereof, or coating or spraying the titanium material with the acid solution.
By these acid treatments, the uneven structure can be effectively formed on the surface of the titanium material. Of course, acids used in the chemical treatment are not limited to these. That is, the depassivation pH of pure titanium is about 1, and if an acid below this pH is used, the uneven structure can be effectively formed by the dissolution and precipitation reaction of the titanium surface.

Furthermore, the acid solution used for the acid treatment contains 50% by weight or more and 97% by weight or less of sulfuric acid, 30% by weight or more and 37% by weight or less of hydrochloric acid, or 20% by weight or more of sulfuric acid and 10% by weight or more of hydrochloric acid. It is preferable that it is a mixture solution containing
By acid treatment using these acid solutions, the uneven structure can be more effectively formed on the surface of the titanium material.

Moreover, the temperature of the solution during the acid treatment is preferably equal to or higher than the melting point of the solution. More preferably, the temperature is 70°C or higher. Also, the upper limit of the temperature is the boiling point of the solution. When the acid treatment is performed at such a high temperature, it is possible to form the uneven structure on the surface of the titanium material in a short period of time of about 10 minutes, and to strengthen the adhesion to the soft tissue of the body. Also, even if the temperature of the solution during the acid treatment is 10° C., a titanium material that can be adhered to the soft tissue of a living body can be obtained if the treatment time is about 12 hours. In addition to immersing the titanium material in the acid solution, the acid treatment can be performed by coating or spraying the acid solution on the titanium material.

Moreover, it is preferable to dry the titanium material after performing the chemical treatment. This drying is preferably performed at 60°C or higher and lower than 600°C.
Immediately after acid treatment in an aqueous solution, the surface of titanium is hydrophilic because water covers it, but it becomes hydrophobic when dried. At this time, drying can be performed at room temperature in atmospheric pressure, but drying can be performed in a short time at 60°C. However, a temperature of 600° C. or higher is not preferable because titanium hydride becomes titanium oxide, and a hydrophobic surface cannot be obtained.

Further, when the acid treatment is performed, the contact angle of water in the air on the surface of the titanium material is preferably 80° or more.
The adhesive strength between the titanium material and the soft tissue of the body changes depending on the treatment time of the acid treatment. It has now been found that titanium materials with angles of approximately 80° or greater have significantly higher adhesion than the untreated state. This is probably because, in the case of acid treatment, the hydrophobic interaction between the hydrophobic surface of the titanium material and the soft tissue of the body contributes to the improvement of the mutual adhesive force. Therefore, it is preferable to carry out the acid treatment on the surface of the titanium material to such an extent that the contact angle of water in the air becomes 80° or more.

Further, when the acid treatment is performed, it is preferable that titanium hydride is deposited on the surface of the titanium material.
The adhesive strength between the titanium material and the soft tissue of the body varies depending on the treatment time of the acid treatment. It was found this time that the adhesive strength was significantly higher than that of the state of . Therefore, the acid treatment should be carried out to the extent that titanium hydride is deposited on the surface of the titanium material.

Moreover, in the bonding method, the chemical treatment may include alkali treatment with a sodium hydroxide solution, a potassium hydroxide solution, a sodium hypochlorite solution, or a mixture thereof.
Even with these alkali treatments, if there are enough OH ⁻ ions, dissolution and deposition reactions proceed, and the uneven structure can be effectively formed on the surface of the titanium material. Of course, the alkali used in the chemical treatment is not limited to these, and any alkali having high water solubility may be used.
In the case of alkali treatment, it is considered that the ionic interaction and the increase in the contact area between the surface of the titanium material and the soft tissue of the body contribute to the improvement of the mutual adhesive force. Therefore, even if the surface of the titanium material is not highly hydrophobic, the adhesion is improved.

Further, in the bonding method, the strength of the chemical treatment may be adjusted to adjust the adhesive force between the titanium material and the soft biological tissue.
This time, it was found that at least the adhesive strength between the titanium material and the soft tissue of the living body was changed by changing the acid treatment time. It is important not only to strengthen the adhesive strength, but also to perform adhesion with an appropriate adhesive strength so that the adhesive can be easily peeled off later. It would be extremely useful if an adhesive with a suitable adhesive strength could be obtained according to the application of the adhesive. It should be noted that the strength can be adjusted not only by the acid treatment time but also by the acid concentration. In addition, it is considered that the strength can be similarly adjusted not only by acid treatment but also by alkali treatment or alkaline acid treatment.

In the adhesion method, the soft biological tissue may be epithelial tissue such as gastrointestinal mucosa and vascular endothelium, muscle, connective tissue including fibrous tissue surrounding organs, blood vessel, or nerve.
If adhesion between the titanium material and epithelial tissue, connective tissue, blood vessels, or nerves can be realized, the above adhesion method can be used for applications such as fixing sensors to living organisms, assisting tissue deformation, sealing perforations in tissue, and reinforcing tissue. easier to do. However, targets for sensor fixation to a living body, tissue deformation assistance, tissue perforation sealing, and tissue reinforcement are not limited to epithelial tissue, connective tissue, blood vessels, and nerves.

The present invention also provides a method for fixing a sensor to a living body using any one of the bonding methods described above, wherein the titanium material has at least a portion of the surface exposed. The sensor is fixed to the living body, and the exposed portion of the surface of the titanium material is brought into contact with the living body soft tissue to bond the titanium material and the living body soft tissue, thereby fixing the sensor to the living body. A method for fixing the sensor to a living body is also provided.

In this method, fixing the sensor and the titanium material in advance can be easily performed by any method such as an adhesive, a fixing device, or fitting. With the sensor fixed to the titanium material, if the surface of the titanium material is brought into contact with the soft biological tissue while applying a slight force, the titanium material is easily adhered to the soft biological tissue in a short period of time, and the sensor is also attached to the titanium material. It is fixed to the living soft tissue through the material. The sensor fixed in this way does not easily shift its position even if the living body moves. Sensors to which this method is applied include, for example, devices that measure the position, movement, physical state, etc. of a living body, or chemical and biological information in the body, and wirelessly transmit the information to an external totalizing device. With the progress of IoT (Internet Of Things) technology, it is believed that the usefulness of efficiently collecting biological information will increase.

The present invention also provides a method for assisting deformation of a soft biological tissue using any of the bonding methods described above, comprising: deforming the soft biological tissue into a desired shape; Also provided is a method for assisting deformation of soft biological tissue, wherein the titanium material is adhered to the soft biological tissue.

At the location where the titanium material is adhered to the soft living tissue, deformation of the soft living tissue is restricted by the titanium material. For example, titanium materials have poor stretchability. For this reason, if a blood vessel or intestinal herniation occurs, the torn part can be prevented from expanding and contracting by pushing the herniated part into the canal through the torn part, closing the torn part, and bonding the titanium material from the outside of the torn part. As a result, it is possible to prevent the torn part from opening and the hernia part from protruding. In addition, since the torn part can be maintained in a closed state, an effect of closing the torn part by natural healing can be expected. This corresponds to assisting the deformation of the living soft tissue so as to close the rupture.

In addition, when the titanium material has a certain rigidity, it is possible to deform the shape of the living body soft tissue where the titanium material is adhered so as to match the shape of the titanium material. Even if there remains a portion where the soft tissue is not adhered to the titanium material due to the difference in shape at first, it is adhered to the titanium material as the tissue contacts the titanium material once or several times according to the movement of the tissue, and the soft tissue becomes soft. This is because the side deforms to conform to the shape of the titanium material. Using this property, for example, it is conceivable to correct the shape of the eyeball for the treatment of myopia by adhering a titanium material having a desired post-correction shape to the back of the eyeball.

The present invention also provides a method for closing a perforation in soft biological tissue using any of the above-described bonding methods, wherein the perforation of the soft biological tissue is covered so as to cover the location where the perforation is formed. There is also provided a method for sealing perforations in soft biological tissue, wherein the titanium material is adhered to the soft biological tissue.
Since the titanium material adhered to the soft tissue of the body adheres closely to the soft tissue of the body, for example, when a perforation occurs in a tissue such as a blood vessel or an intestinal tract, the titanium material is applied so as to cover the perforated site from the outside of the site. The perforations can be closed by adhering. This adhesion may be performed from the outside of the tube or from the inside of the tube using an endoscope and a stent or the like.

The present invention also provides a method for reinforcing soft biological tissue using any one of the bonding methods described above, wherein the titanium material is bonded to a portion of the soft biological tissue to be reinforced. A reinforcement method is also provided.
Even before an injury such as perforation occurs in the tissue, by adhering the titanium material to a portion where the tissue is weakened such as a blood vessel, the tissue can be reinforced and the occurrence of injury can be prevented.

Further, the present invention relates to a titanium material having an uneven structure of nanometer to micrometer size formed on the surface thereof by performing one of acid treatment, alkali treatment, and alkaline acid treatment, and is adhered to biological soft tissue. Also provided is a biosoft tissue adhesive.
This adhesive material for soft tissue of a living body relates to a titanium material that has been chemically treated with an acid treatment, an alkali treatment, or an alkaline acid treatment to form an uneven structure of nano to micrometer size on the surface. Based on the discovery of a new property that it has a strong adhesive force to soft tissue, and that it can adhere to soft tissue in a short period of time by bringing it into contact with the soft tissue while applying a slight force. We propose a novel use of adhesives for soft tissue of living body.

The chemical treatment, the drying, the properties of the titanium material, and the soft biological tissue described above for the bonding method between the titanium material and the soft biological tissue apply equally to this adhesive for soft biological tissue.

The present invention also provides an implantable sensor in which the sensor is fixed to the titanium material of the adhesive for soft biological tissue so that at least part of the surface is exposed.
Such an in-vivo implantable sensor can be easily fixed in a living body by the same principle as described above regarding the fixing method of the sensor in the living body.

The present invention also provides a soft tissue deformation assisting material, a soft tissue perforation sealing material, and a soft tissue reinforcing material, each of which includes the above-described adhesive for soft tissue.
These soft biotissue deformation assisting material, soft biotissue perforation sealing material, and soft biotissue reinforcing material are not limited thereto, but are respectively a method for assisting deformation of soft biotissue, a method for sealing perforation in soft biotissue, and a reinforcement of soft biotissue. available for implementation of the method. That is, based on the discovery of novel properties of titanium materials as described above for adhesives for soft biological tissues, we propose new uses for soft biological tissue deformation assistance, soft biological tissue perforation sealing, and soft biological tissue reinforcement.

In addition, the present invention also proposes an implant having the above adhesive for soft biological tissue in a portion to be adhered to the soft biological tissue. The implant is a dental implant, and preferably includes the above-described adhesive for soft biological tissue in the fixture portion and/or the abutment portion. Alternatively, the implant may be a plastic surgical or cardiovascular surgical implant. Plastic surgical implants are, for example, implants for fixing an auricle prosthesis to the skull. Cardiovascular surgical implants are, for example, tissue penetrating implants, ultrasound echo localizers, tubes penetrating the apex, or endoscopic patches and stents. The present invention also proposes an orthodontic anchor screw that includes the above-described adhesive for soft biological tissue at a portion to be adhered to the soft biological tissue.

All of these are intended to be used by being fixed to a living body, but by providing the above-described adhesive for soft biological tissue in the portion to be adhered to the soft biological tissue, they can be easily fixed to the soft biological tissue. In particular, since the abutment portion of a dental implant is a portion that comes into contact with the gingival mucosal epithelium, the provision of the above-mentioned soft tissue adhesive on this portion facilitates adhesion between the implant and the gingival mucosal epithelium, thereby improving the adhesion of the implant. In addition to enhancing stability, it is possible to prevent invasion of bacteria and the like into the fixture section. Since the fixture part is also in contact with the gingival mucosal epithelium on the side closer to the abutment part, it is useful to similarly provide an adhesive for soft tissue.

The configurations described above and the configurations described in the following embodiments and examples can be arbitrarily combined and implemented as long as they do not contradict each other. Moreover, the configuration described above is an example of the present invention, and the present invention is not limited to the configuration described above.

According to the configuration of the present invention as described above, it is possible to easily adhere a solid member to a living body soft tissue in a short time. Also, this adhesion can be used in a variety of useful applications.

1 is an electron micrograph of a titanium thin film of Example 1. FIG. 4 is an X-ray diffraction pattern of the titanium thin film of the first example. 4 is an FT-IR spectrum of water on the surface of the titanium thin film of Example 1. FIG. 4 is a graph showing the adhesion strength of the titanium thin film of Example 1 to mouse dermis. 4 is an electron micrograph of a titanium thin film of a second example. 4 is an X-ray diffraction pattern of the titanium thin film of the second example. It is a graph which shows the water contact angle of the titanium thin film of 2nd Example. 4 is an FT-IR spectrum of water on the surface of the titanium thin film of Example 2. FIG. 10 is a graph showing the adhesive strength of the titanium thin film of Example 2 to mouse dermis. FIG. 10 is an electron micrograph showing the state of adhesion to the mouse dermis of Example 2. FIG. 4 is a graph showing the adhesive strength of the titanium thin film of Example 2 to rabbit sclera. Fig. 10 is a photograph showing a bonding experiment between the titanium thin film of Example 2 and a porcine aorta. FIG. 10 is a photograph showing the condition after 3 days from adhering the titanium thin film of Example 2 to the subcutaneous dermis side of a mouse. FIG. It is an X-ray-diffraction pattern of the titanium thin film of 3rd Example. It is an electron micrograph of the titanium thin film of the fourth example. 16 is an electron micrograph with a higher magnification for some of the conditions in FIG. 15; FIG. 11 is an electron micrograph of another titanium thin film of the fourth example; FIG. It is an X-ray-diffraction pattern of the titanium thin film of 4th Example. It is a graph which shows the water contact angle of the titanium thin film of 4th Example. FIG. 10 is a graph showing the adhesive strength of the titanium thin film of Example 4 to mouse dermis. FIG. 10 is an electron micrograph of a titanium alloy thin film of a fifth example. It is an X-ray-diffraction pattern of the titanium alloy thin film of 5th Example. 10 is a graph showing the water contact angle of the titanium alloy thin film of Example 5. FIG. 10 is a graph showing the adhesive strength of the titanium alloy thin film of Example 5 to mouse dermis. 1 is a diagram showing the configuration of an embodiment of an in-vivo implantable sensor; FIG. FIG. 26 is a photograph showing how the sensor of FIG. 25 is implanted in the body of a mouse. FIG. 27 is a photograph showing the state of the implantation site in FIG. 26; FIG. FIG. 27 is a photograph showing a state in which the implanted site in FIG. 26 is incised to expose the sensor and a state in which a force is applied to the sensor. FIG. 10 is a diagram for explaining the use of the adhesive for assisting the deformation of a living body soft tissue; FIG. 10 is a diagram for explaining the use of the adhesive material for sealing a perforation in a biological soft tissue; FIG. 3 shows a configuration of a dental implant with adhesive.

EMBODIMENT OF THE INVENTION Hereinafter, the form and Example for implementing this invention are demonstrated.
The present invention relates to a chemical surface modification method for imparting soft tissue adhesiveness to a titanium material, a method for bonding a titanium material imparted with soft tissue adhesiveness to a soft tissue, and a titanium material imparted with soft tissue adhesiveness. Soft biological tissue adhesives composed of materials, their application in several applications, and the like.

Chemical modification of the material surface is used as a method for imparting adhesiveness to biological tissue to titanium materials. The chemical modification method involves introducing functional groups, ions, molecules, etc. to the material surface to increase affinity with adherends, hydrophilic/hydrophobic interactions, ionic bonds, covalent bonds, Van der Waals forces, etc. Connect. Titanium surface modification in the present invention utilizes a chemical modification method to control adhesion.

[First embodiment: FIGS. 1 to 4]
First, a first embodiment of the present invention will be described.
In this example, a thin film (thickness 15 μm×width 5 mm×length 15 mm) of pure titanium (JIS (Japanese Industrial Standard) Class 1 TR270C) was prepared as a titanium material. Samples were prepared by 2) heat treatment, 3) alkali treatment, 4) alkali heat treatment, 5) alkali acid treatment, and 6) alkali acid heat treatment. Of these, 1) and 2) are controls in which neither acid treatment nor alkali treatment is performed.

Each treatment was performed as follows.
1) Untreated:
After degreasing with acetone, it was washed with pure water and dried at 60° C. for 1 hour.
2) Heat treatment:
The sample of 1) was heated at 600° C. for 1 hour in an air atmosphere. This heating also causes drying.
3) Alkali treatment:
The sample of 1) was immersed in a 2.5 mol/L sodium hydroxide solution at 60°C for 24 hours, then washed with pure water and dried at 60°C for 1 hour.
4) Alkali heat treatment:
The sample of 3) was heated at 600° C. for 1 hour in an air atmosphere. This heating also causes drying.
5) Alkaline acid treatment:
The sample of 3) was immersed in a 50 mmol/L hydrochloric acid solution at 37° C. for 48 hours, then washed with pure water and dried at 60° C. for 1 hour.
6) Alkaline acid heat treatment:
The sample of 5) was heated at 600° C. for 1 hour in an air atmosphere. This heating also causes drying.

The surface of the titanium thin film subjected to each of the above treatments was observed by SEM (scanning electron microscope). The SEM was observed using a JSM-6701F microscope (JEOL Ltd., Tokyo, Japan) after osmium coating using Neoc-Pro (Meiwafosis Co. Ltd., Tokyo, Japan). At this time, the observation was made with an acceleration voltage of 5 kV and a working distance of 8 mm.

FIG. 1 shows an electron micrograph of each sample. A scale corresponding to 200 nm (nanometers) is shown in the figure. As can be seen from these photographs, in the samples 3) to 6) subjected to the alkali treatment, a nanofiber-like structure was confirmed as an uneven structure of nano to micrometer size on the surface. In the samples 1) and 2), such nano to micrometer-sized concave-convex structures could not be confirmed.

In addition, the surface crystal structure of the titanium thin film subjected to each of the above treatments was analyzed by measuring the X-ray diffraction (XRD) pattern. XRD patterns were measured using RINT2500HF (Rigaku Corp., Tokyo, Japan). At this time, CuKα rays generated under the conditions of a tube voltage of 40 kV and a tube current of 200 mA were used as an X-ray source, and the scanning speed was 2°/min, and the measurement was performed at room temperature.

FIG. 2 shows the measurement results of each sample.
In samples 1) to 6) that were not heat-treated, that is, samples 1) untreated, 3) alkali-treated, and 5) alkali-acid-treated, only titanium, which is the thin film base material, was detected as a crystal phase. . Among the heat-treated samples, a titanium oxide phase was detected in the samples subjected to 2) heat treatment and 6) heat treatment with alkaline acid. 4) In the alkali heat-treated sample, a sodium titanate phase was detected in addition to the titanium oxide phase.

Further, the water wettability on the surface of the titanium thin film subjected to each of the above treatments was evaluated by determining the contact angle of ultrapure water (3 μL) dropped onto the sample from a height of 10 mm using the θ/2 method.
Table 1 shows the mean and standard deviation of the results (N=5) measured on five samples of titanium thin film for each treatment.

As can be seen from Table 1, water droplets were formed for 1) untreated) and 2) heat treated, indicating some degree of hydrophobicity. With respect to 3) alkaline treatment to 6) alkaline acid heat treatment, water droplets spread on the sample surface, and the water droplet contact angle was 1° or less, which is the detection limit, and these samples exhibited high hydrophilicity.

FT-IR (Fourier Transform Infrared Spectroscopy) spectral analysis of water on each sample surface was also performed. FT-IR spectra were measured using IRAffinity-1S (Shimadzu Corp., Kyoto, Japan). At this time, the resolution was set to 4 cm ⁻¹ and the number of times of accumulation was set to 16, and the measurement was performed at room temperature.

FIG. 3 shows the measurement results of each of the samples 1) to 6).
From these comparisons, it was confirmed that the state of the water on the titanium surface layer changed with the treatment conditions. Here, absorption at 3000 cm ^-1 or less is for water with a developed hydrogen bond network, absorption at 3300 to 3000 cm ^-1 is for intermediate water, absorption at 3500 to 3300 cm ^-1 is for free water, and absorption above 3500 cm ^-1 is for bound water. presumably derived from Among them, water with a developed hydrogen bond network and intermediate water act to suppress the interaction between biological components and materials, so it is important to reduce the amount of these for adhesion to soft tissue. . In the case of 1) untreated and 2) heat-treated, absorption derived from water in which a hydrogen bond network was developed and intermediate water was observed, and 1) absorption on the lowest wave number side was observed in untreated. 3) Alkaline treatment reduced the amount of water in which a hydrogen bond network was developed and the amount of intermediate water. 4) Alkaline heat treatment or 6) Alkaline heat treatment slightly increased the amount of intermediate water. 5) The sharpest free water peak was observed in the alkaline acid treatment.

Next, the adhesive strength between the titanium thin film subjected to each of the above treatments and the soft tissue of the living body was measured. Here, mouse dermal tissue was used as the adherend of the biological soft tissue. The adhesive strength was measured by superimposing a titanium thin film and an adherend in an area of 5 mm × 2 mm, pressing a 100 g weight on the superposed portion for 10 seconds, and then using a universal tester (Ez-test; Shimadzu Corp. ., Kyoto, Japan) was calculated from the maximum force when a shearing force was applied at a tensile speed of 150 mm/min. The mouse dermal tissue used was dermal tissue collected from the back of Slc:ICR mice (6 weeks old; female; body weight 25-27 g). In this case, the titanium thin film and the adherend are bonded by contact for 10 seconds, but the bonding itself can be performed for a shorter period of time, such as 1 to 3 seconds.

Adhesion strength was measured for 5 samples of titanium thin film for each treatment (N=5), and statistical analysis was performed by one-way analysis of variance, followed by multiple comparison test by Tukey method (significance level less than 5%). , 1) to 6), it was analyzed whether or not there was a significant difference in adhesion strength to the soft tissue of the body.

FIG. 4 shows the average value and standard deviation of the adhesive strength obtained for each of the samples 1) to 6). The bar corresponding to each item of 1) to 6) indicates the average value, and the line centered on the upper end indicates the standard deviation. Letters above the bars indicate statistically significant differences in bond strength between samples labeled with different letters. In addition, Table 2 shows the numerical data of the average value and standard deviation of the adhesive strength obtained for each sample.

As can be seen from FIG. 4 and Table 2, the adhesive strength of each sample is ranked in descending order: 5) alkaline acid treatment>6) alkaline acid heat treatment>3) alkali treatment>2) heat treatment=4) alkali heat treatment> 1) untreated.
From these results, it was found that the alkali treatment significantly improved the adhesive strength compared to the untreated case, and that the adhesive strength was able to be used as an adhesive for soft tissue of a living body. It can be seen that the strength increases and that the heat treatment reduces the bond strength obtained by the alkaline or alkaline acid treatment.

In the first embodiment, although the adhesive strength obtained by alkali treatment alone is not so high, it is sufficient in that it adheres to soft tissue and does not move easily. For example, when a 1 g sensor is adhered to an area of 1 mm ² , the adhesive strength that does not move under its own weight is about 10 kPa, and the adhesive strength obtained only by alkali treatment is sufficient. A relatively weak bond strength may also be preferred over a strong bond strength if relatively easy removal after bonding is important.

A comparison of the adhesive strength data in FIG. 4 and Table 2 with the measurement results in FIG. ) In the alkaline acid treatment, it can be considered that the adhesion strength is further improved by increasing the amount of free water. In addition, in 4) alkaline heat treatment or 6) alkaline acid heat treatment, compared to 3) alkaline treatment and 5) alkaline acid treatment, respectively, it is believed that the amount of intermediate water increased, resulting in a decrease in adhesive strength. .

[Second embodiment: FIGS. 5 to 13]
Next, a second embodiment of the invention will be described.
In this embodiment, as the titanium material, the same pure titanium thin film as in the first embodiment is prepared, and this pure titanium thin film is immersed in 45 wt % H ₂ SO ₄ /15 wt % HCl maintained at 70°C. (% by weight is expressed as "wt%" in the following examples). At this time, the treatment time was changed in increments of 5 minutes from 5 minutes to 40 minutes. After the acid treatment, it was washed with pure water and dried at 60° C. for 1 hour.

As a result, the shape of the titanium thin film was maintained from 5 minutes to 20 minutes, but the shape of the titanium thin film was not maintained when the treatment was performed for 25 minutes or more, and it almost completely dissolved after 30 minutes or more. . Therefore, (a) untreated, (b) treated for 5 minutes, (c) treated for 10 minutes, (d) treated for 15 minutes, and (e) treated for 20 minutes, compared to the case of the first embodiment. By the same measurement method, surface observation by SEM, surface crystal structure analysis by XRD pattern measurement, surface wettability measurement, water FT-IR spectrum analysis on the surface, and adhesion strength to living soft tissue were measured. Ta. (a) is a control.

FIG. 5 shows an electron micrograph of each sample obtained by surface observation by SEM. A scale corresponding to 10 μm (micrometers) is shown in the figure.
As can be seen from these photographs, the longer the treatment time, the larger the area where surface dissolution and precipitates are observed. An uneven structure with a size was formed. Base metal grains were observed under the precipitates. When the treatment time was longer, 15 minutes, an increase in precipitates was confirmed, and when the treatment time was 20 minutes, the gaps between the precipitates widened due to re-dissolution of the precipitates or dissolution of the base material, resulting in increased irregularities.

FIG. 6 shows the XRD pattern of each sample.
As can be seen from these patterns, the precipitation of the titanium hydride phase was clearly confirmed when the treatment time was 10 minutes or longer. Moreover, as the treatment time became longer, the peak intensity of the Ti phase, which was the base material, decreased.

FIG. 7 shows the measurement results of surface wettability. The bar corresponding to each treatment time of (a) to (e) indicates the average value of five samples at each treatment time, and the line centered on the upper end thereof indicates the standard deviation. Letters above the bars indicate statistically significant differences in wettability between samples labeled with different letters. The presence or absence of significant difference was analyzed by one-way analysis of variance followed by multiple comparison test (significance level less than 5%) by Tukey's method.

Table 3 shows numerical data of the measurement results of FIG.

As can be seen from these results, the water contact angle significantly increased when the treatment time was 10 minutes or more, indicating high hydrophobicity of 90° or more.

FIG. 8 shows the FT-IR spectrum of water on the sample surface.
A large amount of water with a developed hydrogen bond network and intermediate water was observed in the treatment time of 5 minutes as compared with the untreated case. When the treatment time was 10 minutes or more, the peak derived from intermediate water decreased, but when the treatment time was 10 minutes, a large peak of water with a developed hydrogen bond network was observed at 2900 cm ⁻¹ . When the treatment time was 15 minutes or longer, the absorption of water in which a hydrogen bond network had developed decreased, and almost only bound water was observed.

FIG. 9 shows the average value and standard deviation of the adhesive strength determined for each sample. The notation is the same as in FIG. In addition, Table 4 shows the numerical data of the average value and standard deviation of the adhesive strength obtained for each sample.

As can be seen from FIG. 9 and Table 4, no significant difference in adhesive strength was observed in the samples treated for 5 minutes compared to the untreated samples, but the samples treated for 10 minutes or more showed significant differences. A difference was observed, with longer treatment times indicating higher bond strengths. In addition, the samples treated for 10 minutes or more have adhesive strength that can be used as an adhesive for soft tissue of a living body.
Comparing this data with the SEM photograph of FIG. 5, the XRD pattern of FIG. 6, and the contact angle data of _FIG. ; x = 1.5 to 2) Phase precipitation occurs (Fig. 6), and the acid treatment is performed to the extent that the water contact angle in the air shows a hydrophobicity of about 90 ° or more (in this example, 10 minutes or more). Therefore, it can be seen that the adhesive strength between the titanium material and the soft tissue of the body can be greatly enhanced compared to the untreated case.

Further, by comparing the data of (c) to (e), it can be seen that if the strength of the acid treatment is increased by extending the treatment time, the adhesive strength can be increased in accordance with the treatment strength. Therefore, by adjusting the intensity of the acid treatment, it is possible to adjust the adhesive strength and easily produce a titanium material having a desired adhesive strength.

Next, FIG. 10 shows an electron micrograph of the bonding portion between the titanium thin film and mouse dermis of (e) of the second embodiment. A scale corresponding to 1 μm is shown in the figure. The photographing conditions are the same as in FIGS. 1 and 5 except for the magnification. The left side of the figure shows the titanium thin film, and the right side shows the mouse dermis. From this photograph, it can be seen that the collagen fibers that constitute the dermal tissue are bonded to the titanium surface.

FIG. 11 shows the measurement results of the adhesion strength between the titanium thin film of (d) of the second embodiment and the sclera of the rabbit eyeball. The measurement method was the same as in FIGS. 4 and 9, except that the adherend used was the eyeball of a JW/CSK rabbit (♂; body weight 2.6-3.0 kg). The notation of the figures is also the same as in FIGS. 4 and 9. FIG.
In FIG. 11, the "treated" sample is the titanium thin film (d) of the second embodiment, and the "untreated" sample is the titanium thin film (a). The "sterilized product after treatment" is a sample of the titanium thin film of (d) subjected to autoclave sterilization at 121° C. for 20 minutes. Table 5 shows numerical data of the measurement results shown in FIG.

As can be seen from FIG. 11 and Table 5, even when the object to be adhered is the sclera of the eyeball of a rabbit, the acid treatment for 15 minutes can provide significantly higher adhesion strength than the untreated titanium thin film. Moreover, there is no significant difference in adhesive strength between the presence and absence of autoclave sterilization, and it can be seen that the adhesive strength can be maintained even after autoclave sterilization.

Next, FIG. 12 shows the state of the adhesion experiment between the titanium thin film of the second embodiment (e) and the porcine aorta. A porcine aorta is a living soft tissue that has been taken out of the body and washed.
FIG. 12A shows a titanium thin film 110 in contact with and adhered to a porcine aorta 120 . The titanium thin film 110 can be adhered to the porcine aorta 120 with such a pressing force that the titanium thin film 110 is pinched with tweezers and brought into contact with the porcine aorta 120 . After that, by further pressing the titanium thin film 110 against the porcine aorta 120 with an instrument, fingers, or the like, the bonding strength can be further increased.

(B) shows a state in which the porcine aorta 120 to which the titanium thin film 110 is adhered is bent. Once adhered, the titanium thin film 110 deforms in accordance with the deformation of the tissue even if the tissue to which it is adhered is greatly deformed, and does not separate from the tissue.
(C) shows a state in which the titanium thin film 110 is picked up with tweezers and forcibly pulled off from the porcine aorta 120 by applying a strong force. In the sample of (e), since the adhesive force between the titanium thin film 110 and the porcine aorta 120 is strong, if the titanium thin film 110 and the porcine aorta 120 are forcibly peeled off, the tissue matrix is peeled off together with the titanium thin film 110 .

Next, FIG. 13 shows the condition after 3 days from adhering the titanium thin film of (e) of the second embodiment to the subcutaneous side of the dermis of the mouse. In this example, the treated titanium thin film was cut into small pieces, and the skin was sutured while the titanium thin film was in contact with the dermal side of the incised mouse subcutaneous skin. The adhesion position of the titanium thin film is exposed by pressing the surface. As indicated by symbol A in FIG. 13, even after three days, the titanium thin film did not fall off and remained under the skin on the dermis side, and its position remained the same as when it was first adhered. From this, it can be concluded that the titanium thin film of (e) can firmly adhere to the living soft tissue so that it does not move in vivo even when shear stress is applied between the dermis and fascia for 3 days due to free movement of the mouse. I understand.

[Third embodiment: Fig. 14]
Next, a third embodiment of the invention will be described.
In this embodiment, as the titanium material, _the same pure _titanium thin film as in the first embodiment is prepared. It was washed with pure water and dried at 60° C. for 1 hour. The acid treatment was performed by immersing the titanium thin film in an acid solution at room temperature for 24 hours. Further, the acid solutions used were four types of H ₂ SO ₄ of 10 wt %, 20 wt %, 40 wt % and 70 wt %, and two types of HCl of 15 wt % and 30 wt %.

FIG. 14 shows XRD patterns of titanium thin films after acid treatment under these conditions. The measurement conditions and measurement method are the same as in the first embodiment.
As can be seen from FIG. 14, when using either sulfuric acid or hydrochloric acid, more titanium hydride was deposited as the concentration increased. In sulfuric acid, titanium hydride was observed at concentrations of 20 wt % or higher, and in hydrochloric acid, titanium hydride was observed at concentrations of 15 wt % or higher. At least the samples in which precipitation of titanium hydride is observed have stronger adhesion to soft tissue than untreated samples, and are considered to be usable as adhesives for soft tissue.

[Fourth embodiment: FIGS. 15 to 20]
A fourth embodiment of the present invention will now be described.
In this embodiment, as the titanium material, _the same pure _titanium thin film as in the first embodiment is prepared. It was washed with pure water and dried at 60° C. for 1 hour. The acid treatment was performed by immersing the titanium thin film in an acid solution at room temperature for 12 hours. The acid solutions used were 7 types of 45 wt%, 50 wt%, 60 wt%, 70 wt%, 80 wt%, 90 wt% _, and 97 wt% of _H2SO4 , and 10 wt%, 15 wt%, 20 wt%, and 30 wt% of HCl. , 37 wt %.

15 to 17 show electron micrographs obtained by observing the surface of the titanium thin film after the acid treatment under each condition by SEM. FIG. 16 shows electron micrographs at a higher magnification than the photograph of FIG. 15 for the conditions of 70 wt % and 90 wt %. The measurement conditions and measurement method are the same as in the first embodiment.
As can be seen from FIGS. 15 and 16, when sulfuric acid was used, surface dissolution and deposits were confirmed at a concentration of 50 wt % or higher. Further, as can be seen from FIG. 17, when hydrochloric acid was used, surface dissolution and deposits were confirmed at concentrations of 20 wt % or more.

FIG. 18 shows XRD patterns of titanium thin films after acid treatment under these conditions. The measurement conditions and measurement method are the same as in the first embodiment.
As can be seen from FIG. 18(a), when sulfuric acid was used, titanium hydride was observed at a concentration of 50 wt % or more. Moreover, as can be seen from (b), when hydrochloric acid was used, titanium hydride was observed at a concentration of 20 wt % or higher.

FIG. 19 shows the wettability of the surface of the titanium thin film after the acid treatment under each condition, in terms of the water contact angle in the air. Table 6 shows the numerical data. The measurement conditions and measurement method are the same as in the first embodiment.

As can be seen from FIG. 19 and Table 6, when using either sulfuric acid or hydrochloric acid, the contact angle increased as the concentration increased. The contact angle was 80° or more with sulfuric acid at a concentration of 50 wt% or more, and with hydrochloric acid at a concentration of 20 wt% or more and less than 97 wt%.

FIG. 20 shows the adhesive strength between the titanium thin film and mouse dermal tissue after acid treatment under each condition. Table 7 shows the numerical data. The measurement conditions and measurement method are the same as in the first embodiment.

As can be seen from FIG. 20 and Table 7, sulfuric acid at a concentration of 50 wt % or more and 97 wt % or less and hydrochloric acid at a concentration of 20 wt % or more and 36 wt % or less have an adhesive strength of 10 kPa or more. Adhesion strength was obtained.

[Fifth embodiment: FIGS. 21 to 24]
A fifth embodiment of the present invention will now be described.
In this example, a thin film of titanium-6 aluminum-4 vanadium was prepared as the titanium material, and this titanium alloy thin film was acid-treated by immersing it in 45 wt % H ₂ SO ₄ /15 wt % HCl maintained at 70°C. did At this time, the treatment time was 20 minutes.

FIG. 21 is an electron micrograph obtained by observing the surface of a titanium alloy thin film after acid treatment under these conditions and a titanium alloy thin film subjected to the same treatment as "untreated" in the first embodiment, respectively, by SEM. indicates The measurement conditions and measurement method are the same as in the first embodiment.
As can be seen from FIG. 21, even when a titanium alloy was used, surface dissolution and precipitates were confirmed by acid treatment.

FIG. 22 shows the XRD patterns of the same “acid-treated” and “untreated” titanium alloy thin films. The measurement conditions and measurement method are the same as in the first embodiment.
As can be seen from FIG. 22, titanium hydride was observed by acid treatment even when a titanium alloy was used.

FIG. 23 shows the wettability of the surface of the same “acid-treated” and “untreated” titanium alloy thin films by the water contact angle in air. Table 8 shows the numerical data. The measurement conditions and measurement method are the same as in the first embodiment.

As can be seen from FIG. 23, even when a titanium alloy was used, the contact angle was increased by the acid treatment, and the contact angle became 80° or more after the acid treatment.

FIG. 24 shows the adhesion strength between the same "acid-treated" and "untreated" titanium alloy thin films and mouse dermal tissue. Table 9 shows the numerical data. The measurement conditions and measurement method are the same as in the first embodiment.

As can be seen from FIG. 24 and Table 9, even when a titanium alloy was used, the adhesive strength was increased by acid treatment, and the adhesive strength reached 10 kPa or more.

[Embodiment of in-vivo implantable sensor: FIGS. 25 to 28]
Next, an embodiment of an in-vivo implantable sensor will be described.
As shown in FIG. 25, by fixing the sensor unit 220 on the titanium material 210 which has been chemically treated to strengthen the adhesion to the soft tissue of the living body, as described in the first to fifth embodiments, the in vivo An implantable sensor 200 can be constructed. This fixation may be performed using chemical means such as adhesives, or may be performed using mechanical means such as fitting. In any case, since this step can be performed outside the living body, it can be easily performed.

As shown in FIG. 26, the sensor 200 is attached to the titanium material 210 by bringing the adhesive surface 212 on the opposite side of the sensor unit 220 into contact with the biological soft tissue to be fixed (subcutaneous tissue of a mouse in the example of FIG. 26). Adhesion with the biological soft tissue occurs and can be fixed to the biological soft tissue. Further, even when the soft biological tissue is located on the sensor unit 220 side, the adhesive surface 211 exposed without being covered by the sensor unit 120 is brought into contact with the soft biological tissue, thereby causing adhesion between the titanium material 210 and the soft biological tissue. , can be fixed to biological soft tissue. Of course, both the adhesive surfaces 211 and 212 may be adhered to the living soft tissue.

According to such a configuration, the sensor unit 220 can be reliably implanted and fixed in the living body with a simple operation.
As an example, the titanium thin film of (e) of the second embodiment is used as the titanium material 210, and the skin is sutured while the sensor 200 is brought into contact with and adhered to the incised mouse subcutaneous muscle side as shown in FIG. mice were maintained for 10 days. FIG. 27 shows the appearance of the implanted position from day 1 to day 10. Ten days after the implantation, the implantation position was incised to check the condition of the sensor 200. As shown in FIG. firmly fixed to the subcutaneous tissue. In addition, even when the skin was incised to expose the sensor 200 and pulled with tweezers to apply a strong force, it was confirmed that it adhered to the muscle and that strong adhesion was maintained even after 10 days (Fig. 28 ( b) see).

[Embodiment of soft tissue deformation assisting material: Fig. 29]
Next, an embodiment of the body soft tissue deformation aid will be described.
In this embodiment, as shown in FIG. 29, a hernia 311 formed in an intestinal tract 310, which is a biological soft tissue, is chemically treated as described in the first to fifth embodiments to strengthen the adhesion to the biological soft tissue. This problem is solved by the titanium material 320.
The hernia 311 protruding outside from the torn part of the intestinal tract 310 is pushed into the intestinal tract 310, the torn part is closed, and a titanium material 320 having sufficient adhesive strength is adhered from the outside of the torn part, so that the torn part is closed. It is possible to prevent the hernia from protruding due to the opening of the torn part. In addition, since the torn part can be maintained in a closed state, an effect of closing the torn part by natural healing can be expected.
This corresponds to assisting the deformation of the living soft tissue so as to close the rupture. That is, the titanium material 320 functions as a soft tissue deformation aid.

[Embodiment of sealing material for perforation of biological soft tissue: Fig. 30]
Next, embodiments of the biological soft tissue perforation sealing material will be described.
In this embodiment, as shown in FIG. 30, a perforation 312 formed in an intestinal tract 310, which is a biological soft tissue, is chemically treated as described in the first to fifth embodiments to strengthen the adhesion to the biological soft tissue. This problem is solved by the titanium material 330.
By adhering a titanium material 330 having sufficient adhesive strength from the outside of the intestinal canal 310 so as to cover the perforation 312, the perforation 312 can be sealed and the intestinal canal 310 can be repaired. In addition, since the torn portion of the perforation 312 can be maintained in a closed state, an effect of closing the perforation 312 by natural healing can be expected.

This corresponds to sealing the perforation of the living soft tissue. That is, the titanium material 330 functions as a biosoft tissue perforation sealant. Such a perforation sealing effect can be utilized to seal a perforation accidentally made in the intestinal tract during endoscopic surgery, for example. Even if the titanium material 330 is adhered from the inside of the intestinal tract 310, a similar effect can be exhibited.
In addition, if the titanium material 330 is adhered to the portion where the tissue is weakened before the perforation 312 occurs, the titanium material 330 serves as a biosoft tissue reinforcing material that reinforces the intestinal tract 310 and prevents damage to the intestinal tract 310. Function.

[Embodiment of dental implant: Fig. 31]
Next, embodiments of dental implants will be described.
In this embodiment, as shown in FIG. 31, a first dental implant 400 for embedding in an alveolar bone 510 to fix an artificial tooth 410 has a first As described in the third to third embodiments, a titanium material (adhesive material for soft tissue of a living body) whose adhesion to the soft living tissue is strengthened by chemical treatment is provided. The abutment portion 420 and/or the fixture portion 430 themselves may be formed of such titanium materials.

In this way, the abutment part 420 adheres to the gingival mucosal epithelium 520 when it comes into contact with the gingival mucosal epithelium 520, which is a biological soft tissue. Intrusion of bacteria etc. can be prevented. Since the fixture part 430 is also in contact with the gingival mucosal epithelium 520 on the side closer to the abutment part 420, it is useful to similarly provide an adhesive for soft tissue.

Although a dental implant is used as an example here, other implants such as those for plastic surgery or cardiovascular surgery can also be provided with a similar adhesive material for soft tissue in the part that contacts and adheres to the soft tissue. , providing a ready and strong bond between the implant and soft biological tissue, increasing the stability of the implant and preventing the formation of gaps between the implant and the tissue in which it is implanted.
The same is true for orthodontic anchor screws.

DESCRIPTION OF SYMBOLS 110... Titanium thin film, 120... Porcine aorta, 200... Sensor, 210... Titanium material, 211, 212... Contact surface, 220... Sensor unit, 310... Intestinal tract, 311... Hernia, 312... Perforation, 320, 330... Titanium material, 400... Dental implant, 410... Artificial tooth, 420... Abutment part, 430... Fixture part, 510... Alveolar bone, 520... Gingival mucosal epithelium

Claims (13)

A method for producing a soft biological tissue adhesive for producing a soft biological tissue adhesive for bonding to a soft biological tissue from a titanium material by bringing the titanium material into contact with the soft biological tissue for 1 to 30 seconds, the method comprising:
By subjecting the titanium material to any chemical treatment of acid treatment, alkali treatment, and acid treatment after alkali treatment, an uneven structure of nano to micrometer size is formed on the surface of the titanium material. A method for producing an adhesive for soft biological tissue , comprising a step of forming . 2. The organism of claim 1 , wherein said chemical treatment comprises acid treatment with hydrochloric acid solution, nitric acid solution, sulfuric acid solution, hydrogen peroxide solution, hydrofluoric acid, hydrobromic acid or mixtures thereof. A method for producing a soft tissue adhesive. The chemical treatment comprises an acid treatment by dipping the titanium material in an acid solution that is a hydrochloric acid solution, a sulfuric acid solution, or a mixture thereof, or coating or spraying the titanium material with the acid solution. 3. The method for producing the adhesive for soft biological tissue according to claim 1 or 2 . 4. The method for producing a soft tissue adhesive according to claim 2, further comprising a step of drying the titanium material at 60[deg.] C. or more and less than 600[deg.] C. after the chemical treatment. The chemical treatment is the acid treatment,
5. The adhesive for soft biological tissue according to any one of claims 2 to 4, wherein the surface of the chemically treated titanium material has a water contact angle in air of 80° or more. manufacturing method . The chemical treatment is the acid treatment,
6. The method for producing an adhesive for soft biological tissue according to claim 2, wherein titanium hydride is precipitated on the surface of said chemically treated titanium material. 4. The organism according to any one of claims 1 to 3, characterized in that said chemical treatment comprises an alkaline treatment with sodium hydroxide solution, potassium hydroxide solution, sodium hypochlorite solution or mixtures thereof. A method for producing a soft tissue adhesive. 8. The soft biological tissue according to any one of claims 1 to 7 , wherein the soft biological tissue is gastrointestinal mucosa, epithelial tissue, muscle, connective tissue, blood vessel , nerve , dermal tissue, or sclera. method of manufacturing an adhesive for 9. The method for producing an adhesive for soft biological tissue according to any one of claims 1 to 8, wherein the titanium material is in the form of a thin film.. A rough structure of nano to micrometer size is formed on the surface of the titanium material by subjecting the titanium material to any chemical treatment of acid treatment, alkali treatment, and acid treatment after alkali treatment. preparing a soft biological tissue adhesive from the titanium material by a method comprising the step of :
A method for manufacturing a bio-implantable sensor, wherein the sensor is fixed on the bio-soft tissue adhesive so that at least a part of the surface is exposed. A rough structure of nano to micrometer size is formed on the surface of the titanium material by subjecting the titanium material to any chemical treatment of acid treatment, alkali treatment, and acid treatment after alkali treatment. forming a soft tissue adhesive from the titanium material to be bonded to soft tissue by a method comprising :
A method for manufacturing a soft biological tissue deformation assisting material, wherein the soft biological tissue adhesive is provided at a portion to be adhered to the soft biological tissue. A rough structure of nano to micrometer size is formed on the surface of the titanium material by subjecting the titanium material to any chemical treatment of acid treatment, alkali treatment, and acid treatment after alkali treatment. forming a soft tissue adhesive from the titanium material to be bonded to soft tissue by a method comprising :
A method for producing a soft biological tissue perforation sealing material, wherein the soft biological tissue adhesive is provided in a portion to be adhered to the soft biological tissue. Manufacture of a soft biological tissue reinforcing material for reinforcing the soft biological tissue by adhering the soft biological tissue adhesive to a portion to be adhered to the soft biological tissue and adhering to the soft biological tissue by contacting the soft biological tissue for 1 to 30 seconds. a method,
A method for manufacturing a soft tissue reinforcing material, comprising a step of manufacturing the soft tissue adhesive according to any one of claims 1 to 9 .

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