KR20220070727A - Bioabsorbable membrane for periodontal bone regeneration - Google Patents

Abstract

The present invention relates to a bioabsorbable membrane for regenerating alveolar bone using polydioxanone, which specifically includes a plurality of nanoscale protrusions which upwardly protrude from an upper surface of a polydioxanone membrane, wherein a lower surface of the polydioxanone membrane contains a nano fibrillated cellulose (NFC) membrane, to be widely applied as a membrane for regenerating alveolar bone due to high dimensional stability and improved mechanical strength.

Description

Bioabsorbable membrane for periodontal bone regeneration using polydioxanone

The present invention relates to a membrane for bioabsorbable alveolar bone regeneration using polydioxanone, and in detail, is formed to protrude upward on the upper surface of the polydioxanone membrane and includes a plurality of nanoscale protrusions, The lower surface contains a cellulose nanofiber (nano fibrillated cellulose, NFC) membrane, so it can be widely applied as a membrane for alveolar bone regeneration due to its high dimensional stability and improved mechanical strength.

In dental implants, an appropriate amount of bone is required around the implant as a prerequisite for successful osseointegration and initial stability. If the lack of bone mass-bone volume before implant placement is expected, in the case of exposure of the implant according to the positioning of the implant for normal prosthesis production during implant placement, or if a part of the implant is exposed outside the bone for various reasons after implant placement. In such cases, guided bone regeneration (GBR) is used. In many cases, resorbable and non-absorbable periodontal regeneration membranes and various bone materials (autogenous bone, allogeneic bone, xenogeneic bone, and synthetic bone) are used in the osteoinductive regeneration technique. The membrane for periodontal regeneration is known to prevent the rapid growth of the gingival epithelium from entering the damaged area and to help differentiate the connective tissue and regenerate the bone due to its ability to maintain adequate space. Membrane for periodontal regeneration is largely divided into non-absorbable periodontal regeneration membrane and absorbable periodontal regeneration membrane according to physical properties. Non-absorbable periodontal regeneration membranes include e-PTFE (Expanded-polyetrafluoroehtylene) and titanium mesh. e-PTFE is a periodontal regeneration membrane that has been studied and used for a long time. It is considered as a standard for membranes used in induced regeneration. However, there is a disadvantage that the membrane for periodontal regeneration must be removed through secondary surgery, the membrane for periodontal regeneration tends to be exposed, and the possibility of infection is very high because there is a lot of deposition of plaque once exposed.

On the other hand, polydioxanone (hereinafter PDO) is a polymer approved by the FDA because it is decomposed and disappears within 6 months by hydrolysis in the body, and there is almost no foreign body reaction. However, it has a disadvantage of low mechanical strength, so there is a limit to its use as a membrane for periodontal regeneration. In detail, polydioxanone is known to have excellent biocompatibility and is mainly used as a surgical suture, a lifting thread for plastic surgery, and the like. Compared to other known biodegradable polymers such as PLA, PCL, and PLLA, polydioxanone is a medical polymer material attracting attention due to its minimal immune response, excellent cell compatibility, and rapid biodegradability.

However, polydioxanone products sold on the market are difficult to manufacture in the form of membranes or foams due to polymer chemical properties such as low glass transition temperature and viscosity, high vulnerability to physical thermal processes, and fast decomposition rate. In most cases, only a thread-type suture manufactured through extrusion is manufactured.

Under this background, the present inventors intend to develop a technology for manufacturing a bioresorbable membrane for alveolar bone regeneration using polydioxanone, which is a polymer having the best biocompatibility.

1. Republic of Korea Patent No. 10-1649125 (published on August 11, 2016)

Therefore, the inventors of the present invention use polydioxanone with weak mechanical properties as a biopolymer, but in order to secure mechanical properties such as strength, flexural modulus, and dimensional stability, cellulose nanofibers (nano fibrillated cellulose, NFC) in polydioxanone In the case of including a predetermined amount of or a cellulose nanofiber (nano fibrillated cellulose, NFC) membrane, it was confirmed that it can be suitably used as a bioabsorbable membrane for alveolar bone regeneration, thereby completing the present invention.

Accordingly, it is an object of the present invention to provide a membrane for resorbable periodontal regeneration using polydioxanone.

In order to achieve the above object, the present invention is a polydioxanone (polydioxanone) membrane disposed horizontally; The upper surface of the polydioxanone membrane is formed to protrude upward and includes a plurality of nanoscale protrusions, and the lower surface of the polydioxanone membrane is characterized in that it comprises a cellulose nanofiber (nano fibrillated cellulose, NFC) membrane. It provides a bioresorbable membrane for alveolar bone regeneration.

In addition, the present invention is a horizontally arranged polydioxanone (polydioxanone) membrane; The upper surface of the polydioxanone membrane is formed to protrude upward and includes a plurality of nanoscale protrusions, the polydioxanone (polydioxanone) The membrane provides a bioabsorbable membrane for alveolar bone regeneration, characterized in that it contains 0.1 to 1% by weight of cellulose nanofibers (nano fibrillated cellulose, NFC) based on the total weight of the membrane.

The present invention uses polydioxanone as a biodegradable polymer, but includes cellulose nanofibers to improve its weak mechanical properties, so the adhesion in the oral cavity is strengthened and the shape of the membrane can be preserved for a long time, so it is widely used as an absorbable membrane for periodontal regeneration Available.

In addition, since the membrane for periodontal regeneration of the present invention is decomposed at the time of completion of bone formation, there is no need to separately remove it through secondary surgery.

In addition, it is possible to promote tissue regeneration by providing a high level of surface area by applying a nanopattern on the top layer (surface) instead of using growth factors that may cause side effects.

1 shows a cross-sectional structure of a membrane for periodontal regeneration according to the present invention.
Figure 2 shows the state in which chlorella was attached to the membrane surface of Comparative Example 1 and Example 1.
3 is a graph showing the number of chlorella cells attached to the membranes of Comparative Examples and Examples.
4 is a view of a jig used for measuring tensile strength.
5 is a graph showing the measurement of tensile strength and elongation of the membranes of Comparative Examples and Examples.

The present inventors prepare a membrane for periodontal regeneration using a polydioxanone material suitable as a material for the absorbent periodontal regeneration membrane, but when using cellulose nanofibers (NFC) together to strengthen the mechanical properties of polydioxanone, oral cavity The present invention was completed by finding out that it can be suitably used as an absorbent periodontal regeneration membrane because the adhesion resistance is strengthened and the shape of the membrane can be preserved for a long time.

Accordingly, the present invention is a horizontally disposed polydioxanone (polydioxanone) membrane; The upper surface of the polydioxanone membrane is formed to protrude upward and includes a plurality of nanoscale protrusions, and the lower surface of the polydioxanone membrane is characterized in that it comprises a cellulose nanofiber (nano fibrillated cellulose, NFC) membrane. It provides a bioresorbable membrane for alveolar bone regeneration.

The upper surface of the polydioxanone membrane may be disposed at the defect site of the alveolar bone to regenerate the alveolar bone.

In this case, the upper surface of the polydioxanone membrane may further include a coating film containing saccharides. The coating film exhibits a significant effect in terms of biocompatibility and cell regeneration. In this case, a high concentration of glucose (concentration: 20 to 50 mM) is preferable for the saccharide because it can help tissue recovery and regeneration by causing a local inflammatory reaction. In addition, it may further include a nucleic acid such as DNA or RNA.

The nanoscale protrusion may have a width, a height, and a protrusion interval of 200 to 500 nm. The nanoscale protrusions increase the membrane surface area and help promote regeneration of bone and periodontal tissue.

The polydioxanone preferably has a weight average molecular weight of 100,000 to 1,000,000 and a melt flow index of 3 to 300 g/10min. The purpose is to cover the bone graft material and to prevent the gums from penetrating into the bone due to the difference in the growth rate of bones and gums. There is a limit to performing a role as a membrane for regeneration, and when it exceeds 1,000,000, the viscosity is high and the moldability is poor, and it is preferable to use it within the above range.

The cellulose nanofiber membrane (NFC) of the present invention has superior rigidity than collagen, and can protect the membrane from tearing or external pressure when suturing. In addition, it has excellent biocompatibility, no foreign body reaction in the human body, and has a high surface area and aspect ratio, so it is easy to mix with other materials. In addition, it is mainly used as a reinforcing material due to its high dimensional stability and thermal stability. In particular, the average diameter of the cellulose nanofibers is 50 to 100 nm, and it is preferable to use a length of 200 to 500 μm, because this has the advantage of improving dispersibility in an absorbent polymer such as polydioxanone.

In addition, the thickness of the polydioxanone membrane reinforced with the cellulose nanofibers is preferably 50 to 300 μm. When the thickness of the polydioxanone membrane reinforced with cellulose nanofibers is less than 50 μm, there is a limit to maintaining the shape from external pressure, and when it exceeds 300 μm, the retention period in the body is limited. It is better to use it inside.

In addition, the present invention is a horizontally arranged polydioxanone (polydioxanone) membrane; The upper surface of the polydioxanone membrane is formed to protrude upward and includes a plurality of nanoscale protrusions, the polydioxanone (polydioxanone) The membrane provides an absorbent periodontal regeneration membrane, characterized in that it contains 0.1 to 1% by weight of cellulose nanofibers (nano fibrillated cellulose, NFC) based on the total weight of the membrane.

When the cellulose nanofiber is less than 0.1% by weight, there is a limit to improving strength, and when it is more than 1% by weight, it is preferable to include it within the above range because there is a limit of uniform distribution and dispersibility in polydioxanone.

The nanoscale protrusions may have a width of 200 to 500 nm, a height of 200 to 500 nm, and a protrusion interval of 200 to 500 nm. As mentioned above, the nanoscale protrusions increase the membrane surface area and help promote regeneration of bone and periodontal tissues.

Therefore, the present invention eliminates the need for secondary removal surgery due to polydioxanone, an absorbent polymer with excellent biocompatibility, and increases the strength of the membrane with cellulose nanofibers with superior rigidity than collagen, thereby preventing tearing or external pressure during suturing. It can protect the regenerative area. In addition, it is possible to promote tissue regeneration by providing a high level of surface area by applying a nanopattern on the top layer instead of using growth factors that can cause side effects.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

Comparative Example 1: When there is only PDO membrane without nanoscale protrusions

2% by weight of PDO (weight average molecular weight: 125,00000 to 130,000) was dissolved in HFIP solvent and dissolved using a stirrer at 60° C. for 2 hours to prepare a uniform solution. In this way, the solution was poured onto a glass substrate without a nano-pattern shape, placed in a vacuum oven at 60° C. for 48 hours, the solvent was blown off, and a PDO membrane was obtained from the glass substrate.

Comparative Example 2: When there is a nanoscale protrusion and only a PDO membrane

A PDO membrane was obtained by using a glass substrate having a nano-pattern (protrusion size: horizontal 200 nm, vertical 200 nm, interprotrusion spacing 200 nm) shape in the same manner as in Comparative Example 1.

Comparative Example 3: Membrane containing no nanoscale protrusions, PDO and NFC

For the NFC membrane, 0.5 wt% of NFC was placed in distilled water and the NFC solution dispersed by ultrasonication for 30 minutes was mixed with the previously prepared PDO solution and sonicated to prepare a uniform solution. The solution prepared in this way was poured on a glass substrate without nano-pattern shape, placed in a vacuum oven at 60 ° C. for 48 hours, and the solvent was blown off to finally obtain a PDO membrane reinforced with NFC without nanoscale protrusions.

Example 1: A form in which there is a nanoscale protrusion and a PDO membrane and an NFC membrane are laminated

The prepared PDO solution and NFC 0.5% by weight were put in distilled water and sonicated for 30 minutes to prepare a dispersed NFC solution. Pour the PDO solution on a glass substrate having a nano-pattern shape (protrusion size: horizontal 200 nm, vertical 200 nm, 200 nm spacing between protrusions) with the solution prepared in this way, make a PDO layer with a thickness of 100 μm, and pour NFC solution on it. An NFC layer having a thickness of μm was made, placed in a vacuum oven at 60° C. for 48 hours, and the solvent was blown to finally obtain a membrane in which the PDO membrane and the NFC membrane are laminated.

Example 2: Membrane with Nanoscale Projections and Containing PDO and NFC

NFC solution was prepared by dispersing 0.5 wt% of NFC in distilled water and ultrasonication for 30 minutes. Next, 2% by weight of PDO (weight average molecular weight: 125,00000 130,000) is dissolved in HFIP solvent and dissolved using a stirrer for 2 hours at 60 ° C. prepared. Prepared in this way, the solution was poured on a glass substrate having a nano-pattern (protrusion size: horizontal 200 nm, vertical 200 nm, spacing between protrusions 200 nm), put in a vacuum oven at 60°C for 48 hours, and solvent was added. A PDO membrane reinforced with NFC was obtained by blowing.

Experimental Example 1: Alveolar bone regeneration effect experiment

For the membranes of Comparative Example 1 without nanoscale protrusions and Example 1 with nanoscale protrusions, it was attempted to confirm the affinity with cells according to the presence or absence of nanoscale protrusions. Specifically, chlorella (Chlorella vulgaris, ATCC 9765) was cultured in BG-11 medium at 30° C., diluted 10-fold with distilled water, immersed in each membrane for 30 minutes, and then adsorbed cells were examined under a microscope (Leitz, ORTHOPLANE) through a cell counting technique was performed, and the results are shown in FIGS. 2 and 3 .

As a result of FIG. 2 , in the case of Example 1, which is a polydioxanine membrane with a nanopattern shape, adhered cells can be easily found, whereas in the case of the membrane of Comparative Example 1 without a nanopattern shape, the adhered cells It was confirmed with the naked eye that it was significantly lower.

As a result of FIG. 3 , it was confirmed that the membranes of Examples 1 and 2 having the nanopattern shape had a larger number of cells remaining per unit area than the membrane of Comparative Example 1 without the nanopattern shape. Through these results, it was confirmed that the high surface area can promote tissue regeneration by increasing cell adhesion.

Experimental Example 2: Mechanical Properties - Measurement of Tensile Strength and Elongation

The membranes prepared in Comparative Examples and Examples were fixed to the jig shown in FIG. 4, and the load application rate was applied at 5 mm/min. was measured. In addition, the elongation was measured with the same machine (Universal testing machine (UTM, Instron 3365, Instron)) how much it stretched to the breaking point.

As a result of FIG. 5 , it was confirmed that the membranes of Examples 1 and 2 including NFC had much higher strength than the membranes of Comparative Examples 1 and 2 that did not include NFC. This shows the characteristics of NFC with excellent mechanical strength, and it can be confirmed that even a small amount can serve as a reinforcing material. When a composite material is made with an additive with excellent strength, the ductility is significantly lowered, but it can be confirmed that it is not easily broken because it has a similar elongation (%) value to that of pure PDO due to NFC in the form of fibers. In other words, it was confirmed that the mechanical strength of NFC was improved but did not affect the elongation. Therefore, it is judged that the selection of the NFC material has technical significance in that the mechanical strength is improved without affecting the elongation of the PDO.

As a result of FIG. 6 , it was confirmed that the PDO reinforced with NFC did not easily deform from external force. There was no difference in mechanical strength between the membrane of Example 1 of the laminate structure and the membrane of Example 2 of the single structure.

Therefore, the polydioxanone membrane according to the present invention is formed to protrude upward on the upper surface of the membrane and includes a plurality of nanoscale protrusions, and the lower surface of the polydioxanone membrane has a cellulose nanofiber (nano fibrillated cellulose, NFC) membrane It is an excellent invention that can be widely applied as a membrane for alveolar bone regeneration due to its high dimensional stability and improved mechanical strength.

As the specific parts of the present invention have been described in detail above, for those of ordinary skill in the art, these specific descriptions are only preferred embodiments, and it is clear that the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

The scope of the present invention is indicated by the following claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included in the scope of the present invention.

Claims (7)

Horizontally disposed polydioxanone (polydioxanone) membrane;
The upper surface of the polydioxanone membrane is formed to protrude upward and includes a plurality of nanoscale protrusions,
A bioresorbable membrane for alveolar bone regeneration, characterized in that it comprises a cellulose nanofiber (nano fibrillated cellulose, NFC) membrane on the lower surface of the polydioxanone membrane.
The method of claim 1,
The upper surface of the polydioxanone membrane is disposed on the defect site of the alveolar bone to regenerate the alveolar bone, the bioresorbable membrane for alveolar bone regeneration.
The method of claim 1,
The nanoscale protrusion has a width of 200 to 500 nm, a height of 200 to 500 nm, and a protrusion interval of 200 to 500 nm, a bioabsorbable membrane for alveolar bone regeneration.
The method of claim 1,
The polydioxanone has a weight average molecular weight of 100,000 to 1,000,000, and a melt flow index of 3 to 300 g/10min.
The method of claim 1,
The thickness of the polydioxanone membrane is 50 to 300 μm,
The bioresorbable membrane for alveolar bone regeneration, characterized in that the thickness of the cellulose nanofiber membrane is 30 to 100 μm.
Horizontally disposed polydioxanone (polydioxanone) membrane;
The upper surface of the polydioxanone membrane is formed to protrude upward and includes a plurality of nanoscale protrusions,
The polydioxanone membrane is a bioresorbable membrane for alveolar bone regeneration, characterized in that it contains 0.1 to 1% by weight of cellulose nanofibers (nano fibrillated cellulose, NFC) based on the total weight of the membrane.
7. The method of claim 6,
The nanoscale protrusion has a width of 200 to 500 nm, a height of 200 to 500 nm, and a protrusion interval of 200 to 500 nm, a bioabsorbable membrane for alveolar bone regeneration.

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