JP7618197B2 - Method for promoting bone regeneration - Google Patents

Description

The present invention relates to a method and device for promoting bone regeneration at the site of a fracture or bone defect.

In the treatment of fractures, the broken bone fragments are returned to their original positions and the fractured area is fixed using a cast in conservative treatment or an implant in surgical treatment (see, for example, Patent Document 1). The period until the bone heals thereafter is determined by the bone's inherent regenerative ability. Similarly, in the treatment of bone defects due to disease or trauma, the key is how effectively the bone's inherent regenerative ability can be brought out, and various basic and clinical research is being conducted.

JP 2011-229908 A

If bone regeneration could be promoted in the treatment of fractures and bone defects, it would be possible to reduce the incidence of bone union failure and shorten the treatment period. In this regard, a study calculated based on a US insurance database reported that the incidence of bone union failure after fracture treatment is 5-10%. It is known that the severity of the fracture site, that is, the complexity of the fracture and the presence of bone defects, have a significant impact on bone union. The occurrence of bone union failure not only leads to residual pain and functional impairment, but also brings about a large loss in the medical economy. In this context, the inventors realized that they could make a significant contribution to the medical field by providing technology that enhances the efficiency of bone regeneration through medical-engineering collaboration.

The present invention was made in consideration of these problems, and one of its objectives is to provide a technology that improves the efficiency of bone regeneration in areas of fractures or bone defects.

One aspect of the present invention is a method for promoting bone regeneration. This method includes a target site identification step for identifying the site of a fracture or bone defect, and a plasma supply step for irradiating the site with plasma under atmospheric pressure.

Another aspect of the present invention is a bone regeneration promotion device. This device includes a gas supply unit that supplies a carrier gas under atmospheric pressure toward the site of a fracture or bone defect, and a plasma generation unit that generates plasma in the carrier gas supply path.

The present invention provides a technology that can improve the efficiency of bone regeneration in bone fractures and bone defect sites.

1 is a diagram showing a schematic configuration of a bone regeneration promoting device according to an embodiment. FIG. 2 is a diagram showing a distribution tendency of active species contained in a plasma jet. FIG. 1 is a schematic diagram showing a method for promoting bone regeneration. FIG. 13 is a diagram showing an example of an experiment for verifying the bone regeneration promoting effect according to an embodiment. FIG. 13 is a diagram showing an X-ray image of the area around the target site 8 weeks after surgery. FIG. 13 shows a micro-CT image of the area around the target site 8 weeks after surgery. FIG. 13 is a diagram showing a stained image of the area around the target site 8 weeks after surgery. FIG. 13 is a diagram showing the effect of plasma exposure time on bone regeneration. FIG. 13 is a diagram showing the modifying effect of biological bone by plasma irradiation. FIG. 13 is a diagram showing the modifying effect of biological bone by plasma irradiation.

Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings.
In this embodiment, by directly irradiating a fractured or bone-defective site of a living bone (hereinafter also referred to as a "target site") with plasma, bone formation is promoted in the target site, and bone regeneration efficiency is improved. The method and device are specifically described below.

FIG. 1 is a diagram showing a schematic configuration of a bone regeneration promoting device according to an embodiment.
The bone regeneration promotion device 1 includes a plasma device 10, a gas supply device 12, and a control unit 14. The plasma device 10 functions as a "plasma supply unit" and includes a gas supply pipe 20 through which a carrier gas flows, an electrode 22 provided along the gas supply pipe 20, and a voltage application device 24 that applies a voltage to the electrode 22.

The gas supply pipe 20 is a cylindrical glass tube (dielectric) with a bottom, and has a tapered tip opening. That is, the tip of the gas supply pipe 20 is formed into a hemispherical shape, and a small-diameter outlet 26 for discharging the carrier gas is provided at the tip. The outlet 26 has a diameter φ of 500 to 700 μm (about 650 μm in this embodiment) and is located on the axis of the gas supply pipe 20. Bones have a porous structure, and it is known that the diameter of the gaps (porous spaces) in normal bones is 200 to 500 μm. The diameter φ of the outlet 26 is set to be equal to or slightly larger than the gaps. The rear end opening of the gas supply pipe 20 serves as an inlet for the carrier gas, and is connected to a gas tube 28 of the gas supply device 12.

The electrode 22 is disposed along the outer circumferential surface of the gas supply pipe 20. The electrode 22 is a high-voltage electrode that is disposed coaxially with the gas supply pipe 20, and a voltage application device 24 is connected to the electrode 22. With carrier gas being supplied to the gas supply pipe 20, the voltage application device 24 applies a low-frequency pulse voltage (several kV to 10 kV) of about 10 kHz to the electrode 22, thereby generating a non-equilibrium plasma jet. This plasma jet PJ is a so-called microplasma, and is discharged linearly from the discharge port 26.

The plasma jet PJ is a localized discharge area accompanied by light emission that is periodically ejected from the outlet 26 (nozzle) of the gas supply pipe 20 and appears as a jet. These localized discharge areas are also called "plasma bullets" because their behavior resembles bullets. The movement of these plasma bullets is a mechanism in which an ionization phenomenon propagates through a flux of carrier gas that is prone to discharge. The plasma jet PJ can be said to be the carrier gas itself turned into plasma, and can directly irradiate the target object with plasma.

A housing 29 is provided to cover the gas supply pipe 20 and the electrode 22. The housing 29 is made of a resin such as polytetrafluoroethylene (PTFE) and has insulating properties. The housing 29 is palm-sized.

The gas supply device 12 functions as a "gas supply section" and supplies carrier gas to the plasma device 10. The carrier gas is a gas that propagates plasma, and in this embodiment, helium gas (He) is used. The gas supply device 12 has a gas tank 30. The gas tank 30 is connected to a pipe 32, and a gas tube 28 is connected to the tip of the pipe 32. A control valve 34 is provided on the pipe 32. When the control valve 34 is opened, the carrier gas is supplied to the plasma device 10.

The control unit 14 is made up of a microcomputer having a CPU, ROM, RAM, etc., and controls the power supply to the plasma device 10 and the drive of the gas supply device 12 (controls the opening and closing of the control valve 34). An input device (not shown) is connected to the control unit 14. Based on the user's operation input via the input device, the control unit 14 executes various controls.

Figure 2 shows the distribution tendency of active species contained in the plasma jet. The upper part of the figure shows a visualized image of the plasma jet PJ, and the middle and lower parts show the distribution of active species. The middle part shows positive ions, and the lower part shows negative ions. The horizontal axis of each figure shows the distance from the outlet 26, and the vertical axis shows the amount (intensity) of active species.

The high-brightness parts of the plasma jet PJ contain many charged particles. The charged particles are reduced downstream of the plasma jet PJ (such as the dashed line area in the figure), and many neutral active species (active oxygen species and active nitrogen species) are contained (not shown). In this embodiment, the active species downstream of the plasma jet PJ (downstream of the dashed line in the figure) are actively supplied to the fracture or bone defect site. In other words, bone regeneration is promoted by supplying to the target site plasma with a relatively high proportion of neutral active species compared to the charged particles (described in detail below).

FIG. 3 is a schematic diagram showing a method for promoting bone regeneration.
In this embodiment, in order to promote bone regeneration at a fractured or bone-defected site, plasma is directly irradiated to a target site X of a living bone B. That is, the fractured or bone-defected site is first identified as the target site X, and a portion of the skin corresponding to the target site X is incised to expose the target site X from the incision (target site identification step). Next, while the fractured bone fragments B1 and B2 are repositioned as necessary, a plasma jet PJ is supplied to the target site X (the gap between the bone fragments B1 and B2) (plasma supply step). If the fracture is accompanied by a bone defect, the gap becomes larger.

At this time, in order to efficiently supply the active species (especially neutral active species such as active oxygen species and active nitrogen species) contained in the plasma jet PJ to the target site X, the plasma device 10 is brought appropriately close to the target site X. However, in order to prevent contamination of the living body, the tip of the plasma device 10, i.e., the outlet 26 of the gas supply pipe 20, is adjusted so that it is located outside the periosteum. For example, it may be adjusted so that the tip of the high-brightness part of the plasma jet PJ (see the dashed line in Figure 2) is located at the position of the periosteum.

In the example shown in Figure 3, there is a bone defect, and bone tissue is also present at the back of the target site X (on the extension of the plasma jet PJ). This applies when there is a concave bone defect in the living bone B, or when two bones are adjacent to each other as the living bone B. The experimental example described below (relationship between the ulna and radius) corresponds to the latter case. In this case, as shown by the arrow in the figure, the plasma jet PJ is reflected by the bone surface F at the back, and enters and exits while filling the gap.

Taking into consideration the healing mechanism of the fracture or bone defect site, the flow rate and supply time of the plasma jet PJ are kept to a level that does not dry out the target site X. This is to maintain the occurrence of a hematoma associated with bleeding from the bone marrow in the target site X, and to effectively utilize the various growth factors contained in the hematoma for bone regeneration. In this embodiment, the flow rate of the plasma jet PJ is adjusted to approximately 0.1 to 1 slm. The plasma jet PJ is supplied for a time period during which capillary bleeding (oozing bleeding) is observed, and the plasma irradiation is stopped before hemostasis or coagulation is completed in the target site X.

That is, a hematoma forms at the target site X, filling the defective area of bone and bone marrow tissue. At this time, growth factors such as TGF-β and PDGF are induced, causing the proliferation of granulation tissue and angiogenesis. Then, the cell proliferation phase begins, and undifferentiated mesenchymal cells and osteoblast precursor cells emerge from the granulation tissue. These cells have the ability to later form bone and cartilage. The granulation tissue formed early on also plays an important role as a scaffold for these cells. For this reason, the formation of a hematoma is extremely important for bone regeneration.

In this embodiment, the bone surface at the target site X is modified by plasma irradiation, increasing the affinity with cells that arise during the hematoma formation process (particularly in the early stages of hematoma development) and promoting bone regeneration. Below, we will explain experimental examples conducted to verify this effect.

4A and 4B are diagrams showing an example of an experiment for verifying the bone regeneration promoting effect according to the embodiment, in which (A) and (B) are images taken during the experimental process.
This experiment was an animal experiment using rabbits as subjects. Several rabbits were prepared, and bone defects were artificially created in the ulna of each rabbit, and the effect of the degree of plasma irradiation on bone regeneration was examined. Specifically, the procedure is as follows.

A rabbit was given general anesthesia, the skin of its arm was incised, and a bone defect of about 1 cm was created in the diaphysis of the ulna B10 (Figure 4 (A)). Behind the ulna B10 lies the radius B12. This bone defect corresponds to the target site X. The depth of this bone defect, that is, the distance from the surface of the ulna B10 to the surface of the radius B12, is about 800 μm.

Plasma was irradiated toward the target site X for a specified time (Figure 4 (B)). At this time, the plasma jet PJ was supplied to approximately the center of the target site X. The incision was then closed, and bone union was evaluated after 8 weeks. Note that plasma was irradiated only once, and the amount of new bone was compared when the plasma irradiation time was varied to 5 minutes, 10 minutes, and 15 minutes. As a comparative example, a case where only gas was irradiated without generating plasma using this device (control) was also examined.

To ensure the reliability of the experimental results, five subjects were used for each of the cases of non-plasma irradiation (control), 5-minute irradiation, 10-minute irradiation, and 15-minute irradiation. For these, bone formation was observed using X-rays, and new bone mass was measured using micro-CT. The measurement results were the average of the five subjects. Furthermore, rabbits of similar age and weight were used as experimental subjects so that individual differences in the subjects could be ignored.

Specifically, X-rays were taken of the target site X 2, 4, 6, and 8 weeks after surgery to observe the bone regeneration process. Then, 8 weeks after surgery, a living bone containing the target site X was removed as a specimen, and the amount of newly formed bone was measured based on the micro-CT images. This measurement was performed using software well known in the art, the details of which will not be explained here. Furthermore, each specimen was stained with Masson trichrome stain, and a histological evaluation was performed.

Figure 5 shows X-ray images of the area around the target site 8 weeks after surgery. Figure 5 (A) shows the case of no plasma exposure (control), and Figure 5 (B) shows the case of plasma exposure (10 minutes). The area surrounded by the dashed line shows the area around the target site X. From these, it can be seen that in the case of no plasma exposure, almost no bone formation was observed, whereas in the case of plasma exposure, the amount of bone formation increased significantly. Although not shown in the figure, in the case of plasma exposure, the progress of bone regeneration (change over time) could be observed as the time passed 2 weeks, 4 weeks, and 6 weeks after surgery, but in the case of no plasma exposure, it was hardly observed.

Figure 6 shows micro-CT images of the area around the target site 8 weeks after surgery. Figure 6 (A) shows the case without plasma irradiation (control), and Figure 6 (B) shows the case with plasma irradiation (10 minutes). From these images, it can be seen that in the case without plasma irradiation, almost no new bone formation was observed, whereas in the case of plasma irradiation, the amount of new bone formation increased significantly.

In other words, the bone defect created in this experiment corresponds to a critical defect, which will not heal if left untreated. Nevertheless, it can be seen that supplying the plasma jet PJ to the target site X promotes bone regeneration and enables healing.

Figure 7 shows stained images of the area around the target site 8 weeks after surgery. Figure 7(A) corresponds to the area surrounded by the dashed line in Figure 5(A) and shows the case of non-plasma irradiation (control). Figure 7(B) corresponds to the area surrounded by the dashed line in Figure 5(B) and shows the case of plasma irradiation (10 minutes).

This stained image was obtained by Masson's Trichrome staining, with the white areas representing bone marrow BM, the blue areas representing bone tissue and other fibrous tissue, and the red areas representing muscle fibers, etc. (not shown in color in this figure). Figure 7(A) shows that without plasma irradiation, scar tissue ST such as muscle fibers and collagen fibers remains at the target site X, inhibiting bone regeneration. On the other hand, Figure 7(B) shows that plasma irradiation results in a significant increase in new bone AT at the target site X. In other words, it can be seen that applying plasma irradiation to the target site X during surgery promotes bone union and promotes bone regeneration.

Figure 8 shows the effect of plasma exposure time on bone regeneration. The horizontal axis of this figure shows the plasma exposure time. As a comparison example, a case without plasma exposure (control) is also shown. The vertical axis shows the volume of new bone 8 weeks after surgery.

This experiment shows that the most new bone was obtained when the plasma jet was supplied for 10 minutes. Specifically, when the plasma was irradiated for 10 minutes, the bone regeneration promotion effect was about 1.5 times greater than when the plasma was not irradiated. One of the reasons for the decrease in the amount of new bone when the plasma was irradiated for 15 minutes is thought to be that the target area was dried out by the spraying of the carrier gas, making it difficult to maintain a moist environment at the target area. For this reason, in this embodiment, the plasma irradiation is stopped within the time when capillary bleeding (oozing bleeding) is observed at the target area.

It should be noted that the optimal plasma exposure time may vary depending on the type of living organism and the amount of plasma jet supplied. However, this experiment has made it clear that there are at least optimal values for the supply amount (flow rate) and supply time.

Figures 9 and 10 show the modification effect of biological bone by plasma irradiation. Figure 9 shows an example of an experiment conducted to verify the modification effect. Figure 10 shows the effect of improving hydrophilicity depending on the plasma irradiation time. Figures 10 (A) to (D) show the results of dripping distilled water (water droplets) onto biological bone that had been exposed to plasma for 1 minute, 2 minutes, 3 minutes, and 4 minutes, respectively, and then left for a specified time (30 seconds). Figure 10 (E) shows the case of no plasma irradiation (control) as a comparative example.

As shown in Figure 9, in this experiment, a plasma jet PJ was irradiated for a predetermined period of time (Figure 9(A)) onto a living bone B20 immediately after removal from a subject (rabbit), and then a water droplet L was dropped onto the plasma-irradiated area (Figure 9(B)), and the change in shape of the water droplet L (change in contact angle) was observed.

The results of this experiment show that when plasma is irradiated, the water droplets penetrate into living bone more easily and lose their shape (i.e. the contact angle becomes smaller) as the irradiation time increases (Figures 10 (A) to (D)). After 4 minutes of irradiation, the water droplets became flat and it became impossible to measure the contact angle. On the other hand, when plasma is not irradiated, the shape of the water droplets remains the same and the contact angle does not change.

The experiment was performed five times each for non-plasma exposure (control) and plasma exposure (3 minutes), and the average contact angle was approximately 73 degrees for the former and approximately 45 degrees for the latter. In other words, this experiment verified that plasma exposure for a certain period of time or longer can result in a modification effect on living bone (improved hydrophilicity).

It is possible that the improved hydrophilicity (wettability) caused by plasma irradiation contributes to the promotion of bone regeneration. For example, by increasing the hydrophilicity of the fracture or bone defect site (target site) at the hematoma formation stage, it is thought that the above-mentioned growth factors contained in the hematoma will be more likely to induce osteoblasts, promoting bone regeneration. In other words, it can be considered that plasma irradiation has an effective effect on the hematoma that forms in the bone defect site as an early traumatic response.

After the above experiment, an investigation was carried out into what type of active species were generated by the plasma and how this activated the biological tissue. Specifically, emission spectroscopy was performed to identify the plasma active species, a thermography camera was used to confirm whether or not there was an effect of heat, and the degree of hydrophilization of the bone surface was evaluated. As a result, the generation of OH radicals and excited nitrogen molecules was confirmed. There was no change in the temperature of the surface of the bone defect, and no damage to the biological tissue due to heat was confirmed. The hydrophilicity of the bone tissue surface was improved, and improved adsorption of liquid components in the defect was observed.

These experimental results demonstrate that plasma irradiation of target site X promotes bone union and regeneration. It is possible that plasma irradiation had a positive effect on the activation of surrounding cells and tissues (muscle cells, osteoblasts, nerve cells, mesenchymal cells) and on hematoma formation as an early traumatic response. It is believed that plasma irradiation directly acts on osteoblasts contained in the periosteum of the target site, promoting their differentiation and proliferation, resulting in accelerated healing.

As described above, according to this embodiment, when treating a fracture or bone defect site (target site), bone regeneration can be effectively promoted by irradiating the target site with plasma during the process of hematoma formation. By supplying plasma as a plasma jet, active species that contribute to promoting bone regeneration can be pinpointed and directed to a specific location in the target site. In other words, highly reactive plasma can be sent to the target position (target).

In addition, by adjusting the flow rate of the plasma jet according to the size of the target area, it is possible to prevent the target area from drying out and allow the growth factors contained in the hematoma to function effectively in bone regeneration. The plasma treatment of this embodiment only needs to be used once during surgery or immediately before suturing surgery, which can lead to early recovery of the target area.

In addition, by adjusting the length of the plasma jet according to the depth of the target area, active species effective for bone regeneration can be actively supplied to the target area. Furthermore, by adjusting the plasma irradiation time, it is possible to efficiently increase the amount of new bone. By optimizing the length, flow rate, and irradiation time of the plasma jet, it is expected that the bone regeneration promotion effect can be maximized.

The above describes a preferred embodiment of the present invention, but it goes without saying that the present invention is not limited to this specific embodiment, and various modifications are possible within the scope of the technical concept of the present invention.

In the above embodiment, the plasma device has a single electrode, but a configuration with multiple electrodes may be adopted. Two electrodes may be arranged along the outer circumferential surface of the gas supply pipe. Alternatively, the plasma device may have an external electrode arranged on the outer circumferential surface of the gas supply pipe and an internal electrode arranged inside the gas supply pipe.

In the above embodiment, a cylindrical glass tube with a bottom is exemplified as the gas supply pipe. In a modified example, the tip of the gas supply pipe may be tapered or have another shape. In addition, the material is not limited to glass, and any dielectric material may be used.

In the above embodiment, as an example, a method of irradiating plasma to a target site while reducing fractured bone fragments has been described. In a modified example, reduction treatment may be performed after irradiating plasma to the target site. As shown in the above experimental example, reduction treatment may not be necessary depending on the location of the fracture or bone defect in the living body. In cases of fracture without displacement or deformation, bone defect but continuity is maintained in other areas and the bone morphology is maintained, or bone grafting in spinal surgery (spinal fixation), reduction treatment can be omitted. When transplanting autologous bone, allogeneic bone, artificial bone, or the like to the target site, bone formation can be promoted by irradiating plasma toward the target site (bone graft site).

In the above embodiment, an example was shown in which a plasma jet was supplied to the target area, but plasma that does not have the form of a jet may also be irradiated.

Although not mentioned in the above embodiment, there are conditions known as delayed healing and false joints, in which fracture healing is delayed or does not occur. In treating such delayed healing and false joints, a method may be used in which non-bone tissue (scar, granulation tissue) present in the target area is removed, bleeding from the bone marrow is stimulated, and the target area is fixed with an implant. In such cases, good bone regeneration may be achieved by irradiating the target area with plasma at a timing that stimulates bleeding from the bone marrow.

The above embodiment shows an example in which bone tissue is present deep inside the target area when viewed in the direction of the plasma jet's ejection, that is, an example in which the bone surface that serves as a reflective surface for the carrier gas is present on the extension of the plasma jet. Even when deep bone tissue is not present like this, the surfaces of surrounding tissues such as muscles and ligaments can function as reflective surfaces. In the above embodiment, low-temperature atmospheric pressure plasma (non-equilibrium plasma jet) is used, so safety to these biological tissues can be ensured. In addition, the distribution of active species generated downstream of the plasma jet has a certain degree of spread from the axis of the plasma jet, so the effects of plasma irradiation can be fully expected.

To make the effect more pronounced, the plasma jet may be moved within the bone defect area of the target site. In other words, the plasma jet may be scanned in a direction having a perpendicular component to the ejection direction. Such a scanning mechanism may be provided. The control unit 14 may control the scanning mechanism.

In the above embodiment, the bone regeneration promotion method and device are applied to the field of orthopedics, but they can also be applied to other medical fields such as dental and oral surgery, and neurosurgery. In the dental and oral field, they can also be applied to the regeneration of bone tissue such as the alveolar bone and jawbone, which serve as the base for embedding implants. In the dental and oral field, bone tissue may be exposed before surgery, and it is expected that the skin incision process will not be necessary. In the above embodiment, an example of application to animals (non-humans) was shown as an experimental example, but it goes without saying that they can be applied to humans.

Although not mentioned in the above embodiment, the above bone regeneration promotion method and device can be applied not only to fractures caused by trauma, but also to fractures and bone defects caused by osteoporosis.

In the above embodiment, bone regeneration in fractures with bone defects has been mainly described, but the extent of the effect on fractures without bone defects will have to wait for the results of future research. In other words, bone tissue includes hard cortical bone that forms near the bone surface and soft cancellous bone that forms the interior of the bone. It is not clear at this time which bone tissue the plasma irradiation contributes to the greater regeneration of.

In this regard, if there is a bone defect, the plasma will be irradiated to both, so there is not much need to consider which is more important. On the other hand, if the gap in the fractured area is substantially eliminated by reduction, it may not be easy to introduce plasma into the gap while reducing the area. In such cases, it is preferable to set up the surgical procedure taking into account the bone regeneration effect of plasma irradiation on the cancellous bone.

When plasma irradiation contributes significantly to bone regeneration of cancellous bone, it is advisable to irradiate the plasma while ensuring sufficient gaps between the bone fragments before carrying out reduction procedures. This promotes bone regeneration of cancellous bone and shortens the total time required for fracture healing. On the other hand, when plasma irradiation has little effect on cancellous bone and contributes significantly to bone regeneration of cortical bone, it is preferable to irradiate the plasma while carrying out reduction, as this provides a more stable surgery.

In the above embodiment, an example is shown in which plasma is continuously irradiated for a predetermined time in the plasma supply process. In a modified example, plasma may be irradiated intermittently during the predetermined time. For example, plasma supply may be temporarily stopped every few minutes.

In the above embodiment, helium is used as the carrier gas, but argon, neon, xenon, or other rare gases may also be used, or nitrogen or other gases may also be used. Alternatively, the carrier gas may not be a single type of gas, but may be a mixture of multiple types of gases. For example, a mixture of helium and oxygen may be used as the carrier gas.

The present invention is not limited to the above-mentioned embodiment and modified examples, and the components can be modified without departing from the spirit of the invention. Various inventions can be created by appropriately combining multiple components disclosed in the above-mentioned embodiment and modified examples. In addition, some components can be deleted from all the components shown in the above-mentioned embodiment and modified examples.

1 Bone regeneration promotion device, 10 Plasma device, 12 Gas supply device, 14 Control unit, 20 Gas supply pipe, 22 Electrode, 24 Voltage application device, 26 Discharge port, 28 Gas tube, 29 Housing, 30 Gas tank, 32 Pipe, 34 Control valve, AT Bone tissue, B Living bone, B1 Bone fragment, B10 Ulna, BT Bone tissue, PJ Plasma jet, ST Scar tissue, X Target area.

Claims (4)

A target site identification step of identifying a site of a fracture or bone defect in a non-human animal ;
a plasma supplying step of irradiating only plasma toward the portion under atmospheric pressure;
Equipped with
A method for promoting bone regeneration in a non-human animal , characterized in that the plasma supply step limits the irradiation of the plasma to a period during which capillary bleeding is occurring at the site as part of the process of hematoma formation at the site . The plasma supply step includes:
Supplying a plasma jet toward the portion;
The method for promoting bone regeneration in a non-human animal according to claim 1, characterized in that the flow rate of the plasma jet is adjusted depending on the size of the site. 3. The method for promoting bone regeneration in a non-human animal according to claim 2 , wherein the plasma supply step adjusts the length of the plasma jet depending on the depth of the site. 4. The method for promoting bone regeneration in a non-human animal according to any one of claims 1 to 3, characterized in that in the plasma supplying step, the plasma irradiation time is adjusted depending on the size of the site.

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