JP2020151271A - Method for adhesion of titanium material with soft tissue in vivo, method for fixation of sensor to living body, deformation auxiliary method for soft tissue in vivo, bore hole closing method for soft tissue, reinforcing method for soft tissue, adhesive for soft tissue, living body embedding type sensor, deformation auxiliary material for soft tissue, bore hole closing material for soft tissue and reinforcing material for soft tissue - Google Patents

Abstract

To enable easy adhesion of a solid member with a soft tissue in vivo in a short time.SOLUTION: A method for adhesion of a titanium material with a soft tissue in vivo includes contacting the soft tissue with the surface of the titanium material which forms an uneven structure having the sizes from nano to micrometer by carrying out either chemical treatment among the acid, alkali and alkali-acid treatments. Preferably, the chemical treatment includes the acid treatment by a solution of hydrochloric acid, nitric acid, sulfuric acid or hydrogen peroxide, or hydrofluoric acid, hydrobromic acid or a mixture thereof. Alternatively, the chemical treatment includes preferably an alkali treatment by the solution of sodium hydroxide, potassium hydroxide, sodium hypochlorite, or a mixture thereof.SELECTED DRAWING: Figure 5

Description

The present invention relates to a method of adhering a titanium material to a biosoft tissue, a method of fixing a sensor to a living body, a method of assisting deformation of the biosoft tissue, a method of perforating and sealing the biosoft tissue, a method of reinforcing the biosoft tissue, an adhesive material for the biosoft tissue, and an in vivo. The present invention relates to an implantable sensor, a biosoft tissue deformation assisting material, a biosoft tissue perforation and sealing material, and a biosoft tissue reinforcing material.

Living tissue needs to be restored to its morphology when it is destroyed by external invasion such as trauma or surgery. At present, it is common to use sutures made of silk or a bioabsorbable polymer for this tissue restoration. On the other hand, a biological tissue adhesive may be used as an emergency measure. As the biological tissue adhesive, fibrin glue, cyanoacrylate adhesive and the like are currently used.

On the other hand, in recent years, the development of chips to be embedded in the body has been actively promoted. The implanted chip is used, for example, to monitor changes in the physical, chemical, and biological environment in the body. For this purpose, the implanted chip needs to be held 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 the holding of such a chip in the body for a long period of time.

In addition, titanium is widely used as an implant material in the fields of dentistry and orthopedics as a metal material having high biocompatibility. Conventional methods of use include dental implants, artificial hip joints, bone fixation plates and screws, and bone filling material retention meshes. Immediately after processing, the surface of titanium is passivated to become titanium oxide. It is known that this titanium oxide surface directly bonds (osseointegration) to the bone when it is implanted in the bone for a long period of time such as 4 weeks, but it shows instant adhesion to the soft tissue within a few seconds. Absent.

Special Table 2018-521720

Rupp F, 4 others, "Surface characteristics of dental implants: A review", Dental Materials, 2018, Vol. 34, p.40-57 Luigi Canullo, 5 others, "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, Volume 19, Volume 2. Issue, e177-e183

By the way, the adhesion of living tissues using sutures is an effective method for the purpose of suturing living tissues with each other. However, the success of suturing often depends on the skill of the individual, and time reduction is also desired. Further, in order to connect a non-soft material such as a sensor made of metal or glass and a living tissue by using a suture, it is necessary to give various forms to a hard material such as making a hole in advance.

The fibrin glue and cyanoacrylate adhesives mentioned above are currently widely used in Japan as biological tissue adhesives. However, fibrin glue has advantages and disadvantages that it has excellent biocompatibility but low adhesive strength, and cyanoacrylate adhesive has excellent adhesive strength but low biocompatibility. In addition, cyanoacrylate-based adhesives cause poor curing when there is a lot of water, the structure is broken due to external force applied because the adhesive strength is too high, and when it is removed as necessary. There is also the problem that it is difficult.

Further, since the above-mentioned biological tissue adhesive is used as a liquid, there is a problem that it is easy to move to a part that does not require adhesion or to adhere to a part that does not require adhesion. Further, there is a problem that the operability is inferior because the operation time is limited because the operation can be performed only for the time until the liquid is polymerized and solidified.

Much research has been done on the implantation of titanium materials in vivo, but most of them are for bonding or bonding with hard tissues, not for bonding with soft tissues (non-patent documents). 1). Most of the papers on soft tissue adhesion show that the adhesion with soft tissue occurs after protein adsorption and subsequent cell adhesion (see Non-Patent Document 2), and the living body within a few seconds. There are no reports of events such as adhesion between tissues or adhesion to living tissues. In other words, "tissue adhesion" and "cell adhesion to the substrate" have different meanings just by using the same word "adhesion". The data described in Non-Patent Document 2 is an evaluation of a state in which a dental implant abutment is in contact with soft tissue for one week. Further, since cell adhesion generally requires 6 hours or more, soft tissue adhesion described in Non-Patent Document 2 requires at least 12 hours or more.

Patent Document 1 describes a tissue distribution obtained by etching the surface of a body made of titanium or a titanium alloy with a first etching solution containing mineral acid and then etching with an etching solution containing hydrofluoric acid. Alternatively, it is described that the dental implant abutment is provided on a surface intended to be contacted with bone tissue or soft tissue during use, respectively. 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 4 weeks (see paragraph 0142 of Patent Document 1).

The present invention has been made in view of such circumstances, and an object of the present invention is to enable easy adhesion of a solid member to a biological soft tissue in a short time. Together, we propose various useful uses for this adhesive. The solid member having the ability to adhere to the bio-soft tissue as described above is referred to as an "adhesive" in order to distinguish it from an amorphous adhesive.

One aspect of the present invention for achieving the above object is to form a nano-to-micrometer-sized concavo-convex structure on the surface by performing any chemical treatment of acid treatment, alkali treatment, and alkali acid treatment. This is a method for adhering a titanium material to a biosoft tissue, which comprises contacting the surface of the titanium material with the biosoft tissue to bond the titanium material to the biosoft tissue.

In this method, at least a part of the surface of the titanium material is chemically treated to form a nano-to-micrometer-sized, more specifically, ten-nanometer to several-micrometer-sized concavo-convex structure on that part. , The surface of the titanium material can be imparted with adhesiveness to biological soft tissues. Here, by using a thin film or foil-shaped titanium (hereinafter, titanium thin film), the titanium thin film can be deformed according to the deformation of the flexible soft tissue. In order to provide such deformability, the thickness of the titanium thin film is preferably thin, specifically, the thickness is preferably several hundred nanometers to 100 micrometers.

Further, the above chemical treatment is any of acid treatment, alkaline treatment, and alkaline acid treatment, in which case the surface of the titanium material is dissolved and the dissolved titanium ions react with the solute. It is considered that the uneven structure is formed by the precipitation. The titanium material imparted with adhesiveness can be adhered to the biosoft tissue by bringing it into contact with the biosoft tissue while applying a slight force. In a preferred embodiment, this adhesion can be achieved with a short contact time of about 1 to 30 seconds.

The titanium material before the chemical treatment is not only pure titanium, but also pure titanium containing some impurities and additives to the extent that the adhesiveness to the biological soft tissue after the chemical treatment is not lost. It may be an alloy containing an element other than titanium. Alloys containing other than titanium include, for example, titanium-aluminum-vanadium alloy, titanium-aluminum-molybdenum-vanadium alloy, titanium-aluminum-tin-molybdenum-molybdenum alloy, nickel-titanium alloy, titanium-niob alloy, titanium-niob-tantal. -Molybdenum alloy, titanium-gold-chrome-tantal alloy.

Further, if the titanium material and the biosoft tissue are adhered on both sides of the thin film or plate-shaped titanium material so as to sandwich the titanium material, a plurality of biosoft tissues or biosoft tissues divided into a plurality of parts can be mutually exchanged via the titanium material. Can be glued to. Therefore, the above-mentioned method for adhering the titanium material to the biosoft tissue can also be used as a method for adhering the biosoft tissue to each other using the titanium material.

Further, in the above bonding method, the above chemical treatment may include acid treatment with hydrochloric acid solution, nitric acid solution, sulfuric acid solution, 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 is a hydrochloric acid solution, a sulfuric acid solution or a mixture thereof, or by applying or spraying the acid solution on the titanium material.
By these acid treatments, the uneven structure can be effectively formed on the surface of the titanium material. Of course, the acid used for the above chemical treatment is not limited to these. That is, the demobilization pH of pure titanium is about 1, and if an acid having a pH lower than the same pH is used, the uneven structure can be effectively formed by the dissolution and precipitation reaction of the titanium surface.

Further, the acid solution used for the acid treatment is 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 the acid treatment using these acid solutions, the uneven structure can be more effectively formed on the surface of the titanium material.

Further, the temperature of the solution during the acid treatment is preferably equal to or higher than the melting point of the solution. More preferably, it is 70 ° C. or higher. The upper limit of the temperature is the boiling point of the solution. When the acid treatment is performed at such a high temperature, the uneven structure can be formed on the surface of the titanium material in a short time of about 10 minutes, and the adhesive force to the biological soft tissue can be strengthened. Further, even if the temperature of the solution during the acid treatment is 10 ° C., a titanium material that can be adhered to the biological soft tissue can be obtained if the treatment time is about 12 hours. Further, the acid treatment can be performed not only by immersing the titanium material in the acid solution but also by applying or spraying the acid solution on the titanium material.

Further, 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, water covers the titanium surface, so it is hydrophilic, but when it is dried, it becomes hydrophobic. At this time, it can be dried at room temperature in atmospheric pressure, but it can be dried in a short time at 60 ° C. However, at a temperature of 600 ° C. or higher, titanium hydride becomes titanium oxide, which is not preferable because a hydrophobic surface cannot be obtained.

Further, when the acid treatment is performed, it is preferable that the water contact angle in the air is 80 ° or more on the surface of the titanium material.
The adhesive strength between the titanium material and the biological soft tissue changes depending on the treatment time of the acid treatment, but among multiple samples with different treatment times, the hydrophobicity is higher than in the untreated state, and water contact in the air We have now found that a titanium material with an angle of approximately 80 ° or more has significantly higher adhesive strength than in the untreated state. It is considered that this is because, in the case of acid treatment, the hydrophobic interaction between the hydrophobic surface of the titanium material and the biological soft tissue contributes to the improvement of mutual adhesive force. Therefore, it is preferable to perform the acid treatment on the surface of the titanium material until the water contact angle in the air becomes 80 ° or more.

Further, when the acid treatment is performed, it is preferable that titanium hydride is precipitated on the surface of the titanium material.
The adhesive strength between the titanium material and the biological soft tissue changes depending on the treatment time of the acid treatment, but among the multiple samples with different treatment times, the titanium material in which the precipitation of titanium hydride was confirmed on the surface was untreated. It was found this time that it has a significantly higher adhesive strength than the state of. Therefore, it is advisable to carry out the acid treatment to the extent that titanium hydride is deposited on the surface of the titanium material.

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

Further, in the adhesive method, it is preferable to adjust the adhesive strength between the titanium material and the biological soft tissue by adjusting the strength of the chemical treatment.
At least, it has been found this time that the adhesive force between the titanium material and the biological soft tissue changes by changing the acid treatment time. It is important not only to strengthen the adhesive force but also to bond with an appropriate adhesive force so that the adhesive can be easily peeled off later. It is extremely useful if an adhesive having an appropriate adhesive strength can be obtained according to the application of the adhesive. The strength can be adjusted not only by the acid treatment time but also by the acid concentration. Further, it is considered that the strength can be adjusted in the same manner not only in the case of the acid treatment but also in the case of the alkaline treatment or the alkaline acid treatment.

Further, in the above-mentioned adhesion method, the bio-soft tissue may be epithelial tissue such as gastrointestinal mucosa and vascular endothelium, connective tissue including muscle, bone, cartilage and peri-organ fibrous tissue, 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 will be utilized for applications such as fixing the sensor to the living body, assisting the deformation of the tissue, perforating and blocking the tissue, and reinforcing the tissue. It will be easier to do. However, the objects of fixing the sensor to the living body, assisting the deformation of the tissue, perforating and blocking the tissue, or reinforcing the tissue are not limited to epithelial tissue, connective tissue, blood vessels and nerves.

Further, the present invention is a method for fixing a sensor in a living body by using any of the above-mentioned bonding methods so that at least a part of the surface is exposed to the titanium material. The sensor is fixed to the above-mentioned sensor, and the exposed portion of the surface of the titanium material is brought into contact with the bio-soft tissue to adhere the titanium material and the bio-soft tissue of the living body. It also provides a method of fixing the sensor to the living body, which is fixed in the body.

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, and fitting. If the surface of the titanium material is brought into contact with the biosoft tissue while the sensor is fixed to the titanium material while applying a slight force, the titanium material is easily adhered to the biosoft tissue in a short time, and the sensor is also made of the above titanium. It is fixed to the biological soft tissue via the material. The position of the sensor fixed in this way does not easily shift even if the living body moves. As a sensor to which this method is applied, for example, a device that measures the position, movement, physical state, etc. of a living body, or chemistry and biological information in the body and wirelessly transmits the information to an external aggregation device can be considered. With the progress of IoT (Internet Of Things) technology, it is thought that the usefulness of efficiently collecting biological information will increase.

Further, the present invention is a method for assisting the deformation of a biological soft tissue by using any of the above-mentioned bonding methods, wherein the biological soft tissue is deformed into a desired shape to obtain the deformed shape. Also provided is a method for assisting the deformation of the biological soft tissue, in which the titanium material is adhered to the biological soft tissue.

Where the titanium material is adhered to the biosoft tissue, the titanium material restricts the deformation of the biosoft tissue. For example, titanium material has poor elasticity. Therefore, when a hernia occurs in a blood vessel or intestinal tract, if the hernia part is pushed into the tube from the ruptured part, the ruptured part is closed, and a titanium material is adhered from the outside of the ruptured part, expansion and contraction of the ruptured part is prevented. However, this can prevent the torn portion from opening and the hernia portion from protruding. In addition, since the torn portion can be maintained in a closed state, the effect of closing the torn portion by natural healing can be expected. This corresponds to assisting the deformation of the living soft tissue so that the torn part closes.

Further, when the titanium material has a certain rigidity, it is possible to deform the shape of the biological soft tissue at the portion where the titanium material is adhered to match the shape of the titanium material. Even if there are some areas where the bio-soft tissue is not adhered to the titanium material due to the difference in shape at first, the bio-soft tissue is adhered to the titanium material and is flexible after contacting the titanium material once or several times depending on the movement of the tissue. This is because the side is deformed and follows the shape of the titanium material. Taking advantage of 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 preferable corrected shape to the back side of the eyeball.

Further, the present invention is a method for blocking perforation of a biological soft tissue by using any of the above-mentioned bonding methods, and is described above so as to cover a portion of the biosoft tissue in which the perforation is formed. Also provided is a method for perforating and sealing a living soft tissue in which the titanium material is adhered to the living soft tissue.
Since the titanium material adhered to the living soft tissue adheres to the living soft tissue, 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 part where the perforation is formed from the outside of the perforation. By adhering, the perforation can be closed. This adhesion may be performed from the outside of the tube, or may be performed from the inside of the tube using an endoscope and a stent or the like.

Further, the present invention is a method for reinforcing a biological soft tissue by using any of the above bonding methods, wherein the titanium material is adhered to a portion of the biosoft tissue to be reinforced. Reinforcement methods are also provided.
Even before an injury such as perforation occurs in the tissue, the tissue can be reinforced and the occurrence of the injury can be prevented by adhering the titanium material to the portion where the tissue is weakened in the blood vessel or the like.

Further, the present invention is a titanium material having a nano-to-micrometer-sized uneven structure formed on the surface by performing any chemical treatment of acid treatment, alkali treatment, and alkali acid treatment, and adheres to biological soft tissues. Also provided are biosoft tissue adhesives.
This adhesive for living soft tissues is a living body with respect to a titanium material having a nano-to-micrometer-sized uneven structure formed on its surface by chemically treating any of acid treatment, alkali treatment, and alkali acid treatment. Based on the discovery of a new property that it has a strong adhesive force to the soft tissue and can adhere to the soft tissue in a short time by contacting the soft tissue with a slight force, the soft tissue is formed. It proposes a new application as an adhesive material for biological soft tissues that is adhered to.

The above-mentioned description of the chemical treatment, the above-mentioned drying, the description of the characteristics of the titanium material, and the description of the bio-soft tissue described above for the method of adhering the titanium material to the bio-soft tissue are similarly applied to the bio-soft tissue adhesive.

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

The present invention also provides a biosoft tissue deformation assisting material, a biosoft tissue perforation sealing material, and a biosoft tissue reinforcing material, which are provided with the above-mentioned adhesive for biosoft tissue at a portion to be adhered to the biosoft tissue.
These bio-soft tissue deformation assisting materials, bio-soft tissue perforation-sealing materials, and bio-soft tissue reinforcing materials are, but are not limited to, bio-soft tissue deformation assisting methods, bio-soft tissue perforation-sealing methods, and bio-soft tissue reinforcement, respectively. It can be used to implement the method. That is, based on the discovery of new properties in the titanium material for the bio-soft tissue adhesive as described above, we propose new uses such as bio-soft tissue deformation assistance, bio-soft tissue perforation blockade, and bio-soft tissue reinforcement.

The present invention also proposes an implant in which the above-mentioned adhesive material for biosoft tissue is provided at a portion to be adhered to biosoft tissue. This implant is a dental implant, and the above-mentioned biosoft tissue adhesive may be provided in the fixture portion and / or the abutment portion. Alternatively, the implant may be a plastic or cardiovascular surgical implant. Plastic surgery implants are, for example, implants for fixing the auricle to the skull. Cardiovascular surgical implants are, for example, tissue-penetrating implants, ultrasound echo locating materials, tubes penetrating the apex, or endoscopic patches and stents. The present invention also proposes an orthodontic anchor screw provided with the above-mentioned adhesive material for biosoft tissue at a portion to be adhered to biosoft tissue.

All of these are used by being fixed to a living body, but can be easily fixed to the living soft tissue by providing the above-mentioned adhesive for biosoft tissue in a portion to be adhered to the living soft tissue. In particular, since the abutment part of the dental implant is a part that comes into contact with the gingival mucosal epithelium, by providing the above-mentioned adhesive material for biosoft tissue in this part, the implant and the gingival mucosal epithelium can be easily adhered to each other, and the implant can be used. It is possible to improve the stability and prevent the invasion of bacteria and the like into the fixture part. Since the fixture portion also comes into contact with the gingival mucosal epithelium on the side close to the abutment portion, it is also useful to provide an adhesive for living soft tissues.

The configurations described above and the configurations described in the following embodiments and examples can be implemented in any combination as long as they do not conflict with each other, or only a part thereof can be taken out and implemented. Further, 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 above-described configuration of the present invention, the solid member can be easily adhered to the biological soft tissue in a short time. In addition, this adhesion can be used for various useful applications.

It is an electron micrograph of the titanium thin film of the 1st Example. It is an X-ray diffraction pattern of the titanium thin film of 1st Example. 6 is an FT-IR spectrum of water on the surface of the titanium thin film of the first embodiment. It is a graph which shows the adhesive strength to the mouse dermis of the titanium thin film of 1st Example. It is an electron micrograph of the titanium thin film of the 2nd Example. It is an X-ray diffraction pattern of the titanium thin film of 2nd Example. It is a graph which shows the water contact angle of the titanium thin film of 2nd Example. It is an FT-IR spectrum of water on the surface of the titanium thin film of the second embodiment. It is a graph which shows the adhesive strength to the mouse dermis of the titanium thin film of 2nd Example. It is an electron micrograph which shows the adhesion state to the mouse dermis of the 2nd Example. It is a graph which shows the adhesive strength to the rabbit sclera of the titanium thin film of the 2nd Example. It is a photograph which shows the state of the adhesion experiment between the titanium thin film of 2nd Example, and a porcine aorta. It is a photograph which shows the state 3 days after adhering the titanium thin film of 2nd Example to the dermis side under the skin of a mouse. 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 4th Example. It is an electron micrograph which increased the magnification for some conditions of FIG. It is an electron micrograph of another titanium thin film of the 4th Example. 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. It is a graph which shows the adhesive strength to the mouse dermis of the titanium thin film of 4th Example. It is an electron micrograph of the titanium alloy thin film of the 5th Example. It is an X-ray diffraction pattern of the titanium alloy thin film of 5th Example. It is a graph which shows the water contact angle of the titanium alloy thin film of 5th Example. It is a graph which shows the adhesive strength to the mouse dermis of the titanium alloy thin film of 5th Example. It is a figure which shows the structure of the embodiment of the in-vivo implantable sensor. It is a photograph which shows the state of embedding the sensor of FIG. 25 in a mouse body. It is a photograph which shows the state of the burial place of FIG. It is a photograph which shows the state which exposed the sensor by incising the buried part of FIG. 26, and the state which applied the force to the sensor. It is a figure for demonstrating the biosoft tissue deformation auxiliary use of an adhesive material. It is a figure for demonstrating the use for perforating and sealing a biological soft tissue of an adhesive. It is a figure which shows the structure of the dental implant which has an adhesive.

Hereinafter, embodiments and examples for carrying out the present invention will be described.
The present invention relates to a method relating to chemical surface modification for imparting biosoft tissue adhesiveness to a titanium material, a method for adhering a biosoft tissue adhesive to a biosoft tissue, and titanium having biosoft tissue adhesiveness. The present invention relates to adhesives for biosoft tissues composed of materials, and their applications in some applications.

As a method of imparting biological tissue adhesiveness to a titanium material, a method of chemically modifying the surface of the material is adopted. The chemical modification method is to introduce functional groups, ions, molecules, etc. on the surface of the material to enhance the affinity with the adherend, the interaction in hydrophilicity and hydrophobicity, ionic bond, covalent bond, van der Waals force, etc. Connect. In the titanium surface modification in the present invention, a chemical modification method is used for adjusting the adhesive force.

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

Each process was performed as follows.
1) Unprocessed:
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. Drying is also done by this heating.
3) Alkaline 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) Alkaline heat treatment:
The sample of 3) was heated at 600 ° C. for 1 hour in an air atmosphere. Drying is also done by this heating.
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. Drying is also done by this heating.

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

FIG. 1 shows an electron micrograph of each sample. The scale corresponding to 200 nm (nanometers) is shown in the figure. As can be seen from these photographs, nanofiber-like structures were confirmed on the surface of the samples 3) to 6) that had been subjected to alkali treatment as nano-to-micrometer-sized uneven structures. In the samples 1) and 2), such nano-micrometer-sized uneven 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 an X-ray diffraction (XRD) pattern. The XRD pattern was 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 set to 2 ° / min for measurement at room temperature.

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

Further, the wettability of water 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 by the θ / 2 method.
Table 1 shows the average value and standard deviation of the measurement results (N = 5) for five samples of the titanium thin film for each treatment.

As can be seen from Table 1, water droplets were formed in 1) untreated) and 2) heat treatment, and showed some hydrophobicity. 3) Alkaline treatment ~ 6) For alkaline acid heat treatment, water droplets spread wet on the sample surface, and the water droplet contact angle was below the detection limit of 1 °, and these samples showed high hydrophilicity.

In addition, FT-IR (Fourier Transform Infrared Spectroscopy) spectral analysis of water on the surface of each sample was performed. The FT-IR spectrum was measured using IRAfitity-1S (Shimadzu Corp., Kyoto, Japan). At this time, the resolution was 4 cm ^-1 , the number of integrations was 16, and the measurement was performed at room temperature.

FIG. 3 shows the measurement results of each sample of 1) to 6).
From these comparisons, it was confirmed that the state of water in the titanium surface layer changes depending on the treatment conditions. Here, the water absorption of 3000 cm ^-1 or less hydrogen bond network is developed, the absorption of 3300～3000Cm ^-1 intermediate water, 3500～3300Cm absorption of ^-1 free water absorption of more than 3500 cm ^-1 in the bound water It is thought to be derived. Among these, water and intermediate water with developed hydrogen bond networks act in a suppressive manner on the interaction between biological components and materials, so it is important to reduce these amounts for adhesion to soft tissues. .. In the case of 1) untreated and 2) heat-treated, absorption derived from water with a developed hydrogen bond network and intermediate water was observed, and 1) absorption on the lowest wavenumber side was observed in untreated. 3) Water with a hydrogen bond network developed by alkaline treatment and a decrease in the amount of intermediate water were observed, and 4) alkaline heat treatment or 6) alkaline acid heat treatment slightly increased the amount of intermediate water. 5) In the case of alkaline acid treatment, the peak of free water was observed most sharply.

Next, the adhesive strength between the titanium thin film subjected to each of the above treatments and the biological soft tissue was measured. Here, mouse dermis tissue was used as an adherend of living soft tissue. The adhesive strength is as follows: a titanium thin film and an adherend are superposed on an area of 5 mm × 2 mm, and a 100 g weight is allowed to stand on the superposed portion for 10 seconds to be crimped. It was calculated from the maximum force when a shearing force was applied at a tensile speed of 150 mm / min in Kyoto, Japan). The mouse dermis tissue used was dermis tissue collected from the back of Slc: ICR mice (6 weeks old; ♀; body weight 25-27 g). Here, the titanium thin film and the adherend are adhered by contact for 10 seconds, but the adhesion itself can be performed for a shorter time, for example, about 1 to 3 seconds.

For each treatment, the adhesive strength was measured for 5 samples of titanium thin film (N = 5), one-way ANOVA was performed for statistical analysis, and then multiple comparison test (significance level less than 5%) was performed by Tukey's method. It was analyzed whether or not there was a significant difference in the adhesive strength with the biological soft tissue of the titanium thin films subjected to each of the treatments 1) to 6).

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) shows the average value, and the line centered on the upper end shows the standard deviation. The alphabet above the bar indicates that there is a statistically significant difference in bond strength between samples with different letters. 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, in descending order, 5) alkaline acid treatment> 6) alkaline acid heat treatment> 3) alkaline treatment> 2) heat treatment = 4) alkaline heat treatment>. 1) Unprocessed, in that order.
From this result, it is possible to obtain the adhesive strength that can be used as an adhesive for biological soft tissues by significantly improving the adhesive strength by the alkaline treatment as compared with the case of no treatment, and the adhesive strength by the acid treatment as well as the alkaline treatment. It can be seen that the strength increases and that the heat treatment reduces the adhesive strength obtained by the alkaline treatment or the alkaline acid treatment.

In the first embodiment, the adhesive strength obtained only by the alkaline treatment is not so large, but it is sufficient in that it adheres to the soft tissue and does not move easily. For example, when a 1 g sensor is bonded in an area of 1 mm ² , the bond strength that does not move at least by its own weight is about 10 kPa, and the bond strength obtained only by alkaline treatment is sufficient. Further, when it is important that the adhesive can be peeled off relatively easily after adhesion, a relatively weak adhesive strength may be preferable to a strong adhesive strength.

Comparing the adhesive strength data in FIGS. 4 and 2 with the measurement results in FIG. 3, 3) in the alkaline treatment, the adhesive strength was improved by reducing the amount of water in which the hydrogen bond network was developed and the amount of intermediate water. ) In the alkaline acid treatment, it can be considered that the adhesive strength is further improved by increasing the free water. Further, in 4) alkaline heat treatment or 6) alkaline acid heat treatment, it is considered that the adhesive strength is lowered due to the increase in the amount of intermediate water as compared with 3) alkaline treatment and 5) alkaline acid treatment, respectively. ..

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

As a result, the titanium thin film maintained its shape from the treatment time of 5 to 20 minutes, but the shape of the titanium thin film was not maintained by the treatment of 25 minutes or more, and it was almost completely dissolved in 30 minutes or more. .. Therefore, the samples of (a) untreated, (b) processing time 5 minutes, (c) processing time 10 minutes, (d) processing time 15 minutes, and (e) processing time 20 minutes are the same as in the case of the first embodiment. By the same measurement method, surface observation by SEM, analysis of surface crystal structure by XRD pattern measurement, measurement of surface wettability, FT-IR spectrum analysis of water on the surface, and measurement of adhesive strength with biological soft tissue are performed. It was. (A) is a control.

FIG. 5 shows an electron micrograph of each sample obtained by surface observation by SEM. The scale corresponding to 10 μm (micrometer) is shown in the figure.
As can be seen from these photographs, the surface dissolution and the area where the precipitates are observed tend to increase as the treatment time increases, and the precipitates are observed on almost the entire surface in the treatment time of 10 minutes, from nano to micrometer. An uneven structure of size was formed. Crystal grains of the base metal were observed on the base of the precipitate. At 15 minutes, when the treatment time was longer, an increase in precipitates was confirmed, and at 20 minutes, the irregularities became larger due to the expansion of the gaps between the precipitates due to the redissolution of the precipitates or the dissolution of the base metal.

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 more. Further, 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 the wettability of the surface. The bars corresponding to each of the processing times (a) to (e) indicate the average value of the five samples of each processing time, and the line centered on the upper end indicates the standard deviation. The alphabet above the bar indicates that there is a statistically significant difference in wettability between samples with different letters. The presence or absence of a significant difference was analyzed by performing a multiple comparison test (significance level less than 5%) by the Tukey method after one-way ANOVA.

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

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

FIG. 8 shows the FT-IR spectrum of water on the sample surface.
No significant change was observed at the treatment time of 5 minutes compared to the untreated water, and many waters with developed hydrogen bond networks and intermediate water were observed. When the treatment time was 10 minutes or more, the peak derived from intermediate water decreased, but when the treatment time was 10 minutes, the peak of water with a developed hydrogen bond network of 2900 cm ^-1 was largely observed. When the treatment time was 15 minutes or more, the absorption of water in which the hydrogen bond network was developed decreased, and almost only the bound water was observed.

FIG. 9 shows the average value and standard deviation of the adhesive strength obtained for each sample. The notation is the same as in FIG. 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 FIGS. 9 and 4, no significant difference was observed in the adhesive strength in the sample having a treatment time of 5 minutes as compared with the untreated sample, but it was significant in the sample having a treatment time of 10 minutes or more. A difference was observed, and the longer the treatment time, the higher the adhesive strength. Further, the sample having a treatment time of 10 minutes or more has an adhesive strength that can be used as an adhesive for biological soft tissues.
Comparing this data with the SEM photograph of FIG. 5, the XRD pattern of FIG. 6, and the contact angle data of FIG. 7, nano-micrometer-sized uneven structures were formed (FIG. 5), and titanium hydride (TiH _x ). ; X = 1.5 to 2) Phase precipitation occurs (Fig. 6), and acid treatment is performed until the water contact angle in the air shows hydrophobicity of approximately 90 ° or more (10 minutes or more in this example). Therefore, it can be seen that the adhesive strength between the titanium material and the biological soft tissue can be significantly strengthened as compared with the case of untreated.

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 strengthened according to the treatment strength. Therefore, by adjusting the strength of the acid treatment, the adhesive strength can be adjusted and a titanium material having a desired adhesive strength can be easily produced.

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

FIG. 11 shows the measurement results of the adhesive strength between the titanium thin film (d) of the second embodiment and the rabbit eye sclera. The measurement method is the same as that of FIGS. 4 and 9 except that the adherend used is the eyeball of a JW / CSK rabbit (♂; body weight 2.6 to 3.0 kg). The notation of the figure is the same as that of FIGS. 4 and 9.
In FIG. 11, the “treated” sample is the titanium thin film of (d) of the second embodiment, and the “untreated” is the titanium thin film of (a). The "post-treatment sterilized product" is a sample obtained by autoclaving the titanium thin film (d) at 121 ° C. for 20 minutes. In addition, Table 5 shows the numerical data of the measurement results shown in FIG.

As can be seen from FIGS. 11 and 5, even when the object to be adhered is the rabbit eyeball sclera, a significantly higher adhesive strength can be obtained by the acid treatment for 15 minutes as compared with the case of the untreated titanium thin film. In addition, there is no significant difference in the adhesive strength with and without high-pressure steam sterilization, and it can be seen that the adhesive strength can be maintained even with high-pressure steam sterilization.

Next, FIG. 12 shows a state of an adhesion experiment between the titanium thin film (e) of the second embodiment and the porcine aorta. The porcine aorta is a living soft tissue, which is taken out of the living body and washed.
FIG. 12A shows a state in which the titanium thin film 110 is brought into contact with and adhered to the 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, the titanium thin film 110 can be further pressed against the porcine aorta 120 with an instrument, a finger, or the like to further increase the adhesive strength.

(B) shows a state in which the porcine aorta 120 to which the titanium thin film 110 is adhered is bent. Even if the structure to which the titanium thin film is adhered is greatly deformed in this way, the titanium thin film 110 once bonded is deformed according to the deformation of the structure and does not peel off from the structure.
(C) is a state in which the titanium thin film 110 is pinched with tweezers and forcibly peeled off from the porcine aorta 120 by applying a strong force. In the sample (e), the adhesive force between the titanium thin film 110 and the porcine aorta 120 is strong, so if the sample is forcibly peeled off, the tissue substrate is peeled off together with the titanium thin film 110.

Next, FIG. 13 shows the state 3 days after the titanium thin film of (e) of the second example was adhered to the dermis side under the skin of the mouse. In this example, the treated titanium thin film is cut into small pieces, the skin is sutured in a state where the titanium thin film is brought into contact with the dermis side under the incised mouse, and the mouse is bred for 3 days, and then the skin is incised. The bonding position of the titanium thin film is exposed. As shown by reference numeral A in FIG. 13, the titanium thin film was present on the subcutaneous dermis side without falling off even after 3 days, and its position was the same as that at the time of initial adhesion. From this, the titanium thin film of (e) can be firmly adhered to the soft tissue of the living body so that the mouse does not move in the living body even when a shear stress is applied between the dermis and the fascia for 3 days by freely moving the mouse. I understand.

[Third Example: FIG. 14]
Next, a third embodiment of the present invention will be described.
In this embodiment, as the titanium material, to prepare the thin film of the same pure titanium as in the first embodiment, the pure titanium thin film to, after the acid treatment with H ₂ SO ₄ or HCl at various concentrations, It was washed with pure water and dried at 60 ° C. for 1 hour. The acid treatment was carried out by immersing the titanium thin film in an acid solution for 24 hours at room temperature. The acid solutions used were 4 types of H ₂ SO ₄ of 10 wt%, 20 wt%, 40 wt% and 70 wt%, and 2 types of HCl of 15 wt% and 30 wt%.

FIG. 14 shows the XRD pattern of the titanium thin film after the acid treatment under each of these conditions. The measurement conditions and the measurement method are the same as in the case of the first embodiment.
As can be seen from FIG. 14, when either sulfuric acid or hydrochloric acid was used, more titanium hydride was deposited as the concentration increased. Titanium hydride was observed at a concentration of 20 wt% or more with sulfuric acid, and titanium hydride was observed at a concentration of 15 wt% or more with hydrochloric acid. It is considered that at least the sample in which the precipitation of titanium hydride is observed has a stronger adhesive force to the biosoft tissue than the untreated sample and can be used as an adhesive for the biosoft tissue.

[Fourth Example: FIGS. 15 to 20]
Next, a fourth embodiment of the present invention will be described.
In this embodiment, as the titanium material, to prepare the thin film of the same pure titanium as in the first embodiment, the pure titanium thin film to, after the acid treatment with H ₂ SO ₄ or HCl at various concentrations, It was washed with pure water and dried at 60 ° C. for 1 hour. The acid treatment was carried out by immersing the titanium thin film in an acid solution for 12 hours at room temperature. The acid solutions used were 7 types of H ₂ SO ₄ of 45 wt%, 50 wt%, 60 wt%, 70 wt%, 80 wt%, 90 wt% and 97 wt%, and HCl of 10 wt%, 15 wt%, 20 wt% and 30 wt%. , 37 wt%, 5 types.

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

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

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

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

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

As can be seen from FIGS. 20 and 7, the adhesive strength is 10 kPa or more at a concentration of 50 wt% or more and 97 wt% or less for sulfuric acid and 20% by weight or more and 36 wt% or less for hydrochloric acid, which is sufficient as an adhesive material for biological soft tissues. Adhesive strength was obtained.

[Fifth Example: FIGS. 21 to 24]
Next, a fifth embodiment of the present invention will be described.
In this embodiment, as the titanium material, preparing a thin film of titanium -6 aluminum -4 vanadium, acid treatment by immersing the titanium alloy thin film, a _{45wt% H 2 SO 4 / 15wt} % HCl maintained at 70 ° C. Was done. At this time, the processing time was set to 20 minutes.

FIG. 21 is an electron micrograph obtained by observing the surface of a titanium alloy thin film after acid treatment under this condition and a titanium alloy thin film subjected to the same treatment as the “untreated” of the first embodiment by SEM. Is shown. The measurement conditions and the measurement method are the same as in the case of the first embodiment.
As can be seen from FIG. 21, even when a titanium alloy was used, surface dissolution and precipitation were confirmed by acid treatment.

FIG. 22 shows the XRD pattern of the same “acid-treated” and “untreated” titanium alloy thin films. The measurement conditions and the measurement method are the same as in the case of 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 the air. Table 8 shows the numerical data. The measurement conditions and the measurement method are the same as in the case of the first embodiment.

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

FIG. 24 shows the adhesive strength between the same “acid-treated” and “untreated” titanium alloy thin films and the mouse dermis tissue. Table 9 shows the numerical data. The measurement conditions and the measurement method are the same as in the case of the first embodiment.

As can be seen from FIGS. 24 and 9, even when the titanium alloy was used, the adhesive strength was increased by the acid treatment, and the adhesive strength was 10 kPa or more, and sufficient adhesive strength was obtained as an adhesive material for biosoft tissues.

[Embodiment of Implantable Sensor in Living Body: FIGS. 25 to 28]
Next, an embodiment of the in-vivo implantable sensor will be described.
As shown in FIG. 25, by fixing the sensor unit 220 on the titanium material 210 whose adhesive force to the biological soft tissue has been strengthened by chemical treatment as described in the first to fifth embodiments, the sensor unit 220 is in vivo. An embedded sensor 200 can be configured. This fixing may be performed by using a chemical means such as an adhesive or by a 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 brought into contact with the titanium material 210 by bringing the adhesive surface 212 on the opposite side of the sensor unit 220 into contact with the biosoft tissue to which it is fixed (the subcutaneous tissue of the mouse in the example of FIG. 26). Adhesion to the living soft tissue occurs and can be fixed to the living soft tissue. Further, even when the biosoft tissue is located on the sensor unit 220 side, the titanium material 210 and the biosoft tissue are adhered by bringing the exposed adhesive surface 211, which is not covered by the sensor unit 120, into contact with the biosoft tissue. , Can be fixed to living soft tissue. Of course, both of the adhesive surfaces 211 and 212 may be adhered to the biological soft tissue.

According to such a configuration, the sensor unit 220 can be reliably embedded and fixed in the living body by a simple operation.
As an example, using the titanium thin film of (e) of the second embodiment as the titanium material 210, the skin is sutured in a state where the sensor 200 is brought into contact with and adhered to the muscle side under the skin of the incised mouse as shown in FIG. The mice were bred for 10 days. FIG. 27 shows the appearance of the burial position from the 1st day to the 10th day. Ten days after the implantation, the implantation position was incised and the state of the sensor 200 was confirmed. As shown in FIG. 28A, the position of the sensor 200 in the body was the same as that at the time of implantation, and the surroundings It was firmly fixed to the subcutaneous tissue. Further, it was confirmed that even when the skin was incised to expose the sensor 200 and a strong force was applied by pulling with tweezers, the skin adhered to the muscle and the strong adhesion was maintained even after 10 days (FIG. 28 (FIG. 28). b) See).

[Embodiment of bio-soft tissue deformation aid: FIG. 29]
Next, an embodiment of the biological soft tissue deformation assisting material will be described.
In this embodiment, as shown in FIG. 29, the hernia 311 formed in the intestinal tract 310, which is a living soft tissue, is chemically treated as described in the first to fifth embodiments to enhance the adhesive force to the living soft tissue. This is solved by the titanium material 320.
If the hernia 311 protruding outward from the ruptured portion of the intestinal tract 310 is pushed into the intestinal tract 310, the ruptured portion is closed, and the titanium material 320 having sufficient adhesive strength is adhered from the outside of the ruptured portion, the ruptured portion is formed. It can be closed and the torn part can be prevented from opening and the hernia part from protruding. In addition, since the torn portion can be maintained in a closed state, the effect of closing the torn portion by natural healing can be expected.
This corresponds to assisting the deformation of the living soft tissue so that the torn part closes. That is, the titanium material 320 functions as a biological soft tissue deformation auxiliary material.

[Embodiment of biological soft tissue perforation encapsulant: FIG. 30]
Next, an embodiment of the biological soft tissue perforation encapsulant will be described.
In this embodiment, as shown in FIG. 30, the perforation 312 formed in the intestinal tract 310, which is a living soft tissue, is chemically treated as described in the first to fifth embodiments to enhance the adhesive force to the living soft tissue. This is solved by the titanium material 330.
If a titanium material 330 having sufficient adhesive strength is adhered from the outside of the intestinal tract 310 so as to cover the perforation 312, the perforation 312 can be sealed and the intestinal tract 310 can be repaired. Further, since the ruptured portion of the perforation 312 can be maintained in a closed state, the effect of closing the perforation 312 by natural healing can be expected.

This corresponds to sealing the perforation of living soft tissue. That is, the titanium material 330 functions as a biological soft tissue perforation encapsulant. Such a perforation sealing effect can be utilized, for example, to seal a perforation that has been accidentally opened in the intestinal tract during endoscopic surgery. The same effect can be obtained by adhering the titanium material 330 from the inside of the intestinal tract 310.
Further, if the titanium material 330 is adhered to the portion where the tissue is weakened before the perforation 312 occurs, the titanium material 330 reinforces the intestinal tract 310 and prevents the intestinal tract 310 from being damaged, as a biosoft tissue reinforcing material. Function.

[Dental implant embodiment: FIG. 31]
Next, an embodiment of the dental implant will be described.
In this embodiment, as shown in FIG. 31, the first is on at least the surface of the abutment portion 420 and / or the fixture portion 430 of the dental implant 400 to be embedded in the alveolar bone 510 to fix the artificial tooth 410. A titanium material (adhesive material for biosoft tissue) whose adhesive strength to biosoft tissue is strengthened by chemical treatment as described in the third embodiment is provided. The abutment portion 420 and / or the fixture portion 430 itself may be formed of such a titanium material.

In this way, the abutment portion 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, to enhance the stability of the dental implant 400 and to the fixture portion 430. It is possible to prevent the invasion of bacteria and the like. Since the fixture portion 430 also comes into contact with the gingival mucosal epithelium 520 on the side close to the abutment portion 420, it is useful to provide a biosoft tissue adhesive in the same manner.

Here, a dental implant is taken as an example, but other implants such as those for plastic surgery or cardiovascular surgery can also be in contact with the bio-soft tissue, and the bio-soft tissue adhesive is similarly provided at the portion to be adhered to the implant. , The implant and the living soft tissue can be prepared and strongly adhered to improve the stability of the implant and prevent the formation of a gap between the implant and the tissue to be implanted.
The same applies to the orthodontic anchor screw.

110 ... Titanium thin film, 120 ... Pig 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 (25)

By performing any of the chemical treatments of acid treatment, alkali treatment, and alkali acid treatment, the surface of the titanium material having a nano-to-micrometer-sized uneven structure formed on the surface is brought into contact with the biological soft tissue. , A method for adhering a titanium material to a biosoft tissue, which comprises adhering the titanium material to the biosoft tissue. The titanium according to claim 1, wherein the chemical treatment includes acid treatment with a hydrochloric acid solution, a nitric acid solution, a sulfuric acid solution, a hydrogen peroxide solution, hydrofluoric acid, hydrofluoric acid or a mixture thereof. How to bond the material to the biological soft tissue. The chemical treatment is characterized by including acid treatment by immersing the titanium material in an acid solution which is a hydrochloric acid solution, a sulfuric acid solution or a mixture thereof, or by applying or spraying the acid solution on the titanium material. The method for adhering a titanium material according to claim 1 or 2 to a biological soft tissue. The method for adhering a titanium material to a biological soft tissue according to claim 2 or 3, wherein the titanium material is dried at 60 ° C. or higher and lower than 600 ° C. after the chemical treatment. The method for adhering a titanium material to a biological soft tissue according to any one of claims 2 to 4, wherein the surface of the titanium material has a water contact angle in the air of 80 ° or more. The method for adhering a titanium material to a biological soft tissue according to any one of claims 2 to 5, wherein titanium hydride is precipitated on the surface of the titanium material. The titanium according to any one of claims 1 to 3, wherein the chemical treatment includes an alkali treatment with a sodium hydroxide solution, a potassium hydroxide solution, a sodium hypochlorite solution or a mixture thereof. How to bond the material to the biological soft tissue. The titanium material and living body according to any one of claims 1 to 7, wherein the adhesive strength between the titanium material and the biological soft tissue is adjusted by adjusting the strength of the chemical treatment. Adhesion method with soft tissue. The method for adhering a titanium material to a living soft tissue according to any one of claims 1 to 8, wherein the living soft tissue is an epithelial tissue, connective tissue, blood vessel or nerve. A method for fixing a sensor to a living body by using the method for adhering a titanium material and a living soft tissue according to any one of claims 1 to 9 to fix the sensor in the living body.
The sensor is fixed to the titanium material so that at least a part of the surface is exposed.
The sensor is fixed in the living body by bringing the exposed portion of the surface of the titanium material into contact with the living soft tissue and adhering the titanium material and the living soft tissue of the living body. The method of fixing the sensor to the living body. A method for assisting the deformation of a living soft tissue by using the method for adhering a titanium material and a living soft tissue according to any one of claims 1 to 9.
The biological soft tissue is deformed into a desired shape,
A method for assisting deformation of a living soft tissue, which comprises adhering the titanium material to the living soft tissue along the shape after the deformation. A method for blocking perforation of a biosoft tissue by using the method for adhering a titanium material and a biosoft tissue according to any one of claims 1 to 9.
A method for sealing a perforation of a biosoft tissue, which comprises adhering the titanium material to the biosoft tissue so as to cover a portion of the biosoft tissue in which the perforation is formed. A method for reinforcing a biological soft tissue by using the method for adhering a titanium material and a biological soft tissue according to any one of claims 1 to 9.
A method for reinforcing a biological soft tissue, which comprises adhering the titanium material to a portion of the biological soft tissue to be reinforced. A titanium material having nano to micrometer-sized uneven structures formed on its surface by chemical treatment of any of acid treatment, alkali treatment, and alkaline acid treatment, and is adhered to biosoft tissues for biosoft tissues. Adhesive. The living body according to claim 14, wherein the chemical treatment includes acid treatment with a hydrochloric acid solution, a nitric acid solution, a sulfuric acid solution, a hydrogen peroxide solution, hydrofluoric acid, hydrofluoric acid or a mixture thereof. Adhesive for soft tissues. The chemical treatment is characterized by including acid treatment by immersing the titanium material in an acid solution which is a hydrochloric acid solution, a sulfuric acid solution or a mixture thereof, or by applying or spraying the acid solution on the titanium material. The adhesive for biosoft tissue according to claim 14 or 15. The biosoft tissue adhesive according to claim 15, wherein the titanium material is dried at 60 ° C. or higher and lower than 600 ° C. after the chemical treatment. The adhesive for biosoft tissues according to any one of claims 15 to 17, wherein the surface of the titanium material has a water contact angle in the air of 80 ° or more. The adhesive for biosoft tissue according to any one of claims 15 to 18, wherein titanium hydride is precipitated on the surface of the titanium material. The living body according to any one of claims 14 to 16, wherein the chemical treatment includes an alkali treatment with a sodium hydroxide solution, a potassium hydroxide solution, a sodium hypochlorite solution or a mixture thereof. Adhesive for soft tissues. The adhesive for biosoft tissue according to any one of claims 14 to 20, wherein the biosoft tissue is an epithelial tissue, connective tissue, blood vessel or nerve. Implantation in a living body of the adhesive for biosoft tissue according to any one of claims 14 to 21, wherein the sensor is fixed to the titanium material so that at least a part of the surface is exposed. Type sensor. A biosoft tissue deformation assisting material, which comprises the biosoft tissue adhesive according to any one of claims 14 to 21 provided on a portion to be adhered to the biosoft tissue. A biosoft tissue perforation / sealing material comprising the adhesive for biosoft tissue according to any one of claims 14 to 21 on a portion to be adhered to the biosoft tissue. A biosoft tissue reinforcing material comprising the adhesive for biosoft tissue according to any one of claims 14 to 21 on a portion to be adhered to the biosoft tissue.