SPECIFICATION

MEMBRANE SYSTEM FOR FORMING BONE WITHOUT GRAFT

TECHNICAL FIELD

The present invention relates to a novel bone formation method which eliminates graft usage. More particularly, the present invention relates to an antimicrobial membrane system which can be resorbed and which can preserve its shape thanks to its rigid structure, and particularly relates to the application method thereof.

PRIOR ART

Bone losses, due to different reasons, are frequently faced. For instance, after tooth extraction, rapid bone thinning occurs in the jaw bone. The jaw thinning occurring in the bone after tooth extraction continues at the maximum level within the first 3 months period, it continues in a rapid manner within the next 3 months period, and it continues in a slow manner after the 6 ^th month. There are pluralities of applications for the treatment of bone losses occurring in this type or in different forms.

For the prosthesis for treatment purposes, there has to be bone and mucosa support with substantial amount and quality. Substantial amount of bone is needed for implant application or without implant application. Guided tissue regeneration methods have been used for long years where bone grafts and membranes are used for formation of new bone. The bone graft is the surgical placement of bone tissue or bone-forming materials to the bone grafting region. The grafts can be obtained from the patient or they can be obtained from different sources. The grafts, taken from the body of the patient, are called autogenic graft. The grafts, which can be obtained from outside, are in three types; i. Allografts (Human Sourced Grafts)

ii. Xenografts (Animal Sourced Grafts)

iii. Synthetic Grafts (Grafts with Chemical Mixture)

There are various problems related to the grafts presently used. Particularly, in products obtained from different sources (from different humans and animals), the risk of infectious disease cannot be completely eliminated, and they may show antigenic property. Moreover, the cost of these products is high. Membranes shall be used together with grafts. There are various membranes. There are membranes which resorb, in other words, said membranes are thinned and eliminated after being placed to the body, or there are membranes which do not resorb, in other words, said membranes are not thinned and eliminated. Particularly the membranes which do not resorb and which can preserve their shapes (like titanium supported polytetrafluoroethylene) are expensive products. Moreover, they have to be removed by means of a second surgical operation. In the market, in general, membranes which can be resorbed (like collagen) and which are more economic are used. These membranes permit movement or displacement of the graft, which is in granule or powder form and provided under the membranes, since they cannot preserve the shapes thereof (since they are not rigid). Moreover, it is recommended that the membranes are mostly fixed by means of bone tacs, however, this is generally not applied in practice since cost is high and since application is difficult. Therefore, reaching of the soft tissue cells to the area is facilitated. Due to said reasons, the amount and quality of the obtained bone cannot be exactly predicted.

Gel membrane, used for a similar purpose and comprising polyethylene glycol, has been recently placed on the market by a company. This product functions by hardening after being applied onto the graft placed inside the mouth. These types of products cannot be used without using bone graft.

Due to the present disadvantages in the prior arts, an improvement, which is robust, economic, predictable, antibacterial and easily applicable, is required in the technical field related to crest augmentation.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to a new membrane system and the application thereof, for eliminating the above mentioned disadvantages and for bringing new advantages to the related technical field.

In the light of the known state of the art, the main object of the present invention is to provide elimination of the need for bone graft by using autogenic blood together with a membrane system which is completely resorbed in the body. Another object of the present invention is to provide elimination of the disease infection risk thanks to the application of a membrane which is completely resorbed in the body and to recommend an antibacterial method. Another object of the present invention is to provide development of an economic membrane system which is easily applicable.

Another object of the present invention is to reduce duration of the surgical operation and invasiveness and to reduce the cost and to make patient acceptance and application widespread.

In order to realize all of the abovementioned objects, the present invention is a novel membrane system used in tooth implant applications. In order to realize all of the abovementioned objects and the objects which are to be deducted from the detailed description below, said membrane system is characterized by comprising an antimicrobial polymer which can be resorbed or a membrane formed by polymer mixture and an autogenic as the graft alternative. In a preferred application of the subject matter invention, said autogenic comprises the selected one of or the mixture of blood, bone morphogenetic protein (BMP-2 or BMP-7) or platelet derivative growing factor (PDGF), fibrin which is rich in platelet (PRF), plasma which is rich in platelet (PRP) or fibrin which is rich in platelet (PRF). In another preferred application of the subject matter invention, said polymer is polylactic acid.

In another preferred application of the subject matter invention, said polymer is polyethylene glycol. In a preferred application of the subject matter invention, said polymer is the mixture of polylactic acid and polyethylene glycol.

In another preferred application of the subject matter invention, the proportion of said polylactic acid to the polyethylene glycol mixture is 85/15 by mass.

In another preferred application of the subject matter invention, the proportion of said polylactic acid to the polyethylene glycol mixture is 75/25 by mass. In another preferred application of the subject matter invention, the proportion of said polylactic acid to the polyethylene glycol mixture is 60/40 by mass. In another preferred application of the subject matter invention, the molecular weight of said polyethylene glycol is (mw) 8000.

In another preferred application of the subject matter invention, said polymer or polymer mixture also comprises glycolic acid polymer. Said glycolic acid polymer has molecular weight between 190000 and 240000, and it is a Poly(D,L-lactide-co-glycolic) with proportion 85/15 %.

In another preferred application of the subject matter invention, said membrane system moreover comprises antimicrobial substance.

In another preferred application of the subject matter invention, the antimicrobial substance in said membrane system is caffeic acid phenetile ester (CAPE).

In another preferred application of the subject matter invention, said membrane system moreover comprises tissue adhesive.

In another preferred application of the subject matter invention, said tissue adhesive is cya no- aery I ate. In another preferred application of the subject matter invention, bone wax or fibrin adhesive or cyano-acrylate is used for closing the holes existing on said membrane surface.

In another preferred application of the subject matter invention, said membrane system comprises screw.

In another preferred application of the subject matter invention, said screw supports said membrane from any region of the surface thereof.

In another preferred application of the subject matter invention, said prosthesis is completely resorbed within a period greater than 6 months. In another preferred application of the subject matter invention, said membrane is applied to the alveolar crestal defects existing in the jaws.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: i. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

ii. Cutting the membrane so as to cover all edges of the defect and adhering thereof to the related region by means of the tissue adhesive,

iii. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the punched hole,

iv. Covering the region with suture primarily,

v. Applying implant after bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: vi. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

vii. Placing a screw, which is aligned so as to support the membrane from the bottom surface, to the region where the membrane is to be applied,

viii. Cutting the membrane so as to cover all edges of the defect, and adhering thereof to the related region in a rigid manner by means of tissue adhesive,

ix. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the punched hole,

x. Covering the region with suture primarily,

xi. Removing the screw and applying implant after bone formation. Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: xii. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

xiii. Placing a tooth implant to the region, where the membrane is to be applied, so as to support the membrane from the bottom surface and in a position planned for the prosthesis, xiv. Cutting the membrane so as to cover all edges of the defect, and adhering thereof to the related region in a rigid manner by means of tissue adhesive,

xv. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the punched hole,

xvi. Covering the region with suture primarily and

xvii. Applying prosthesis above the implant after new bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: xviii. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

xix. Cutting the membrane so as to cover all edges of the defect, and adhering particularly the lingual/palatine edge to the related region in a rigid manner by means of tissue adhesive,

xx. Placing BMP-2, BMP-7, PDGF, PRF or PRP (applied with the carrier or which has solid consistence), which accelerate bone formation, to the cavity,

xxi. Adhering the remaining other edges of the membrane,

xxii. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the punched hole,

xxiii. Covering the region with suture primarily,

xxiv. Applying implant after bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: xxv. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

xxvi. Placing a screw, which is aligned so as to support the membrane from the bottom surface, to the defect region,

xxvii. Cutting the membrane so as to cover all edges of the defect, and adhering particularly the lingual/palatine edge to the related region in a rigid manner by means of tissue adhesive,

xxviii. Placing BMP-2, BMP-7, PDGF, PRF or PRP (applied with the carrier or which has solid consistence), which accelerate bone formation, to the cavity,

xxix. Adhering the remaining other edges of the membrane, xxx. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the punched hole,

xxxi. Covering the region with suture primarily,

xxxii. Removing the screw and applying implant after bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: xxxiii. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

xxxiv. Placing a tooth implant to the region, where the membrane is to be applied, so as to support the membrane from the bottom surface and in a position planned for the prosthesis,

xxxv. Cutting the membrane so as to cover all edges of the defect, and adhering particularly the lingual/palatine edge to the related region in a rigid manner by means of tissue adhesive,

xxxvi. Placing BMP-2, BMP-7, PDGF, PRF or PRP (applied with the carrier or which has solid consistence), which accelerate bone formation, to the cavity,

xxxvii. Adhering the remaining other edges of the membrane,

xxxviii. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the punched hole,

xxxix. Covering the region with suture primarily,

xl. Applying prosthesis above the implant after new bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: xli. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

xlii. Cutting the membrane so as to cover all edges of the defect, and adhering all edges to the related region in a rigid manner,

xliii. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the punched hole,

xliv. Injecting BMP-2, BMP-7, PDGF or PRP (in liquid form), which accelerate bone formation, to the cavity, and covering the punched hole,

xlv. Covering the region with suture primarily,

xlvi. Applying implant after bone formation. Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: xlvii. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

xlviii. Placing a screw, which is aligned so as to support the membrane from the bottom surface, to the defect region,

xlix. Cutting the membrane so as to cover all edges of the defect, and adhering all edges to the related region in a rigid manner,

I. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the punched hole,

li. Injecting BMP-2, BMP-7, PDGF or PRP (in liquid form), which accelerate bone formation, to the cavity, and covering the punched hole,

lii. Covering the region with suture primarily,

liii. Removing the screw and applying implant after bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: liv. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

Iv. Placing a tooth implant to the region, where the membrane is to be applied, so as to support the membrane from the bottom surface and in a position planned for the prosthesis,

Ivi. Cutting the membrane so as to cover all edges of the defect, and adhering all edges to the related region in a rigid manner,

Ivii. Punching said membrane surface, and filling autogenic blood into the formed gap, Iviii. Injecting BMP-2, BMP-7, PDGF or PRP (in liquid form), which accelerate bone formation, to the cavity, and covering the punched hole,

lix. Covering the region with suture primarily,

Ix. Applying prosthesis above the implant after new bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of:

Ixi. Applying anesthesia to the region to which membrane system is to be applied, Ixii. Cutting the membrane so as to cover all edges of the defect, and adhering thereof to the related region in a hermetic and rigid manner by means of tissue adhesive, Ixiii. Punching said membrane surface, and filling autogenic blood into the formed gap, Ixiv. Covering the punched hole on the membrane.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of:

Ixv. Applying anesthesia to the region to which membrane system is to be applied, Ixvi. Placing a screw, which is aligned so as to support the membrane from the bottom surface, to the region to which the membrane is to be applied,

Ixvii. Cutting the membrane so as to cover all edges of the defect, and adhering thereof to the related region in a hermetic and rigid manner by means of tissue adhesive, Ixviii. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the membrane surface,

Ixix. Removing the screw existing at the bottom surface of the membrane prior to implant application.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of:

Ixx. Applying anesthesia to the region to which membrane system is to be applied, Ixxi. Placing a tooth implant to the region, where the membrane is to be applied, so as to support the membrane from the bottom surface,

Ixxii. Cutting the membrane so as to cover all edges of the defect, and adhering thereof to the related region in a hermetic and rigid manner by means of tissue adhesive, Ixxiii. Punching said membrane surface, and filling autogenic blood into the formed gap, Ixxiv. Covering the punched hole on the membrane. Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of:

Ixxv. Applying anesthesia to the region to which membrane system is to be applied, Ixxvi. Cutting the membrane, comprising polylactic acid and polyethylene glycol, so as to cover all edges of the defect, and adhering thereof to the related region in a hermetic and rigid manner by means of tissue adhesive cyano-acrylate, Ixxvii. Punching said membrane surface, and filling autogenic blood into the formed gap, Ixxviii. Applying implant after bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of:

Ixxix. Applying anesthesia to the region to which membrane system is to be applied,

Ixxx. Placing a screw to the region, where the membrane system is to be applied, so as to support the membrane from the bottom surface,

Ixxxi. Cutting the membrane, comprising polylactic acid and polyethylene glycol, so as to cover all edges of the defect, and adhering thereof to the related region in a hermetic and rigid manner by means of tissue adhesive cyano-acrylate,

Ixxxii. Punching said membrane surface, and filling autogenic blood into the formed gap,

Ixxxiii. Covering the punched hole on the membrane.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of:

Ixxxiv. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

Ixxxv. Placing a screw to the defect region so as to support the membrane from the bottom surface,

Ixxxvi. Cutting the membrane so as to cover all edges of the defect, and adhering particularly the lingual/palatine edge to the related region in a rigid manner by means of tissue adhesive,

Ixxxvii. Placing BMP-2, BMP-7, PDGF, PRF or PRP (applied with the carrier or which has solid consistence), which accelerate bone formation, to the cavity,

Ixxxviii. Adhering the remaining other edges of the membrane,

Ixxxix. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the punched hole,

xc. Covering the region with suture primarily,

xci. Removing the screw and applying implant after bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: xcii. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method, xciii. Placing a tooth implant to the region, where the membrane is to be applied, so as to support the membrane from the bottom surface and in a position planned for the prosthesis,

xciv. Cutting the membrane so as to cover all edges of the defect, and adhering particularly the lingual/palatine edge to the related region in a rigid manner by means of tissue adhesive,

xcv. Placing BMP-2, BMP-7, PDGF, PRF or PRP (applied with the carrier or which has solid consistence), which accelerate bone formation, to the cavity, xcvi. Adhering the remaining other edges of the membrane,

xcvii. Punching said membrane surface, and filling autogenic blood into the formed gap, and covering the punched hole,

xcviii. Covering the region with suture primarily,

xcix. Applying prosthesis above the implant after new bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: c. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

ci. Cutting the membrane so as to cover all edges of the defect, and adhering all edges to the related region in a rigid manner,

cii. Punching said membrane surface, and filling autogenic blood into the formed gap, ciii. Injecting BMP-2, BMP-7, PDGF or PRP (in liquid form), which accelerate bone formation, to the cavity, and covering the punched hole,

civ. Covering the region with suture primarily,

cv. Applying implant after bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: cvi. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

cvii. Placing a screw, which is aligned so as to support the membrane from the bottom surface, to the defect region,

cviii. Cutting the membrane so as to cover all edges of the defect, and adhering thereof to the related region in a rigid manner,

cix. Punching said membrane surface, and filling autogenic blood into the formed gap, ex. Injecting BMP-2, BMP-7, PDGF or PRP (in liquid form), which accelerate bone formation, to the cavity, and covering the punched hole,

cxi. Covering the region with suture primarily and

cxii. Removing the screw and applying implant after bone formation.

Another preferred application of the subject matter invention relates to the application method of the membrane system for crest augmentation, comprising the steps of: cxiii. Applying anesthesia to the region to which membrane system is to be applied, and removing flap by means of a suitable method,

cxiv. Placing a tooth implant to the region, where the membrane is to be applied, so as to support the membrane from the bottom surface and in a position planned for the prosthesis,

cxv. Cutting the membrane so as to cover all edges of the defect, and adhering thereof to the related region in a rigid manner,

cxvi. Punching said membrane surface, and filling autogenic blood into the formed gap, cxvii. Injecting BMP-2, BMP-7, PDGF or PRP (in liquid form), which accelerate bone formation, to the cavity, and covering the punched hole,

cxviii. Covering the region with suture primarily and

cxix. Removing the screw and applying implant after bone formation.

THE DETAILED DESCRIPTION OF THE INVENTION

In this detailed description, the subject matter membrane system is explained with references to examples without forming any restrictive effect only in order to make the subject more understandable.

The autogenic statement comprises the selected one of or the mixture of blood, bone morphogenetic protein (BMP-2 or BMP-7) or platelet derivative growing factor (PDGF), fibrin which is rich in platelet (PRF), plasma which is rich in platelet (PRP) or fibrin which is rich in platelet (PRF).

The proportion of said polylactic acid (PLA) to the polyethylene glycol (PEG) of said membrane is 85/15%, 75/25%, 60/40% by mass. The average mole mass of PLA is Mn=20000, the average mole mass of PEG is Mw=8000. The film thickness is going to be 0,2 mm. However, the thickness is between 0, 1 and 0,5 mm, and it is going to vary depending on the treatment and the region where application is to be realized. Example;

Polylactic acid (PLA) and polyethylene glycol (PEG) are dried under high vacuum at 60°C for 6 hours before the mixing process. The PLA/PEG proportion in the mixture is preferred to be 85/15%, 75/25%, 60/40% by mass depending on the resorbing duration. The PLA/PEG mixture is prepared by using a double-screw conventional extruder. In order to produce membrane, an intermittent film line is assembled to the extruder with laboratory scale. The shell temperature of the extruder during the process is 175°C, the screw speed is 120 rpm, and the retention duration is 5 minutes. In order to prevent thermo-oxidative degradation during mixing, the inner section of the shell is cleaned by means of nitrogen gas. In order to provide film at a fixed speed at the end of the mixing process, the extruder is in force control mode. The film line is adjusted such that the film thickness is between 0, 1 and 0,5 mm, and the width is 25 mm, and the films are cooled by means of air knife at the end of the head.

The caffeic acid phenetile ester (CAPE) is obtained by means of separating the ethanolic extract of the propolis, collected naturally from the bee hives, by means of colon chromatography. Saturated solution of the CAPE in ethanol is prepared and it is passed through a filter of 0,22 μητι.

Preparation of the antimicrobial membranes: The membranes are waited for 1 night inside CAPE solution filtered after being cut at approximate sizes depending on the purpose of use. The membranes, impregnated by CAPE, are dried under vacuum at 30 °C for 6 hours.

It is important to resorb the membrane for a long time duration (approximately 6 months or above). After tooth and bone losses occurring in the region of the jaws called alveolar crest and which carries the teeth, membrane is applied around the defect occurring in this region. The membrane can be used in a standalone manner (tent screw or tent pole); alternatively, screw can be used for increasing membrane support. It may also be preferred to directly place the implant without using screw, since this is going to decrease the number of surgical operation steps.

Anesthesia is provided in the related field by means of appropriate local anesthesia (when required, general anesthesia) methods. The region is reached by means of incision methods known so as to make out the whole defect. The membrane is cut so as to cover all edges of the defect (so as to overrun by 2-3 mm). After the flap is removed, the membrane is adhered so as to completely cover all edges of the defect. The membrane is applied firstly to the lingual of the lower jaw, and to the palatine side of the upper jaw. Tissue adhesive (a tissue-compliant cyano-acrylate or another tissue adhesive) is applied to the edges of the membrane. While the other regions are adhered, the tissue adhesive is applied in a very thin line form to the membrane or to the edges of the bone defect, and the remaining section of the membrane is completely adhered. Therefore, the rigidity of the membrane is increased which is completely adhered to the edges of the bone and which has become into a saddle form. Moreover, the soft tissue cells, forming the base of the guided tissue regeneration, are completely prevented from reaching the related region.

Before placing the membrane, implant can be placed to the defect region by means of known methods. The tooth implant to be used has a bone level design. The tooth implant and the membrane are placed to the desired bone height. Another option is to place screw into the bone defect. In this method, the head section of the placed screws is brought to the same alignment as the membrane which is to be placed. By means of this, it is going to support the membrane and the rigidity is going to be increased. After bone formation, these screws shall be removed before placing the implant.

In the next step, it is aimed to completely fill the inner section of this gap with blood. Therefore, a hole is formed by means of a fissure drill from the highest region of the formed volume with respect to the patient position. This hole is going to be used for autogenic blood injection, and it shall be greater than the diameter of the injector needle. When the hole is formed at a region so as to correspond to the bone and on the membrane provided at the border of the bone defect, an angle of approximately 45 degrees is formed towards the cavity. Thus, covering the hole after injection is facilitated.

In the next step, blood, which is equal in volume to the volume of the defect, is taken from the patient by means of known methods. Only the blood can be directly injected to the region, or while the blood is being injected, it may be mixed with bone morphogenetic protein (BMPs) like BMP-2 or 7 or platelet derivative growing factor (PDGF), plasma which is rich in platelet (PRP). Another alternative is the placement of fibrin which is rich in platelet (PRF) to the cavity before the membrane is placed. All of these methods are methods which are known to accelerate bone formation. The growing factors and other products, which accelerate bone formation, can also be used together with the controlled emission preparates. An important advantage of this method is that it can present alternative solutions for patient populations who have different needs and different conditions.

The own blood of the person is injected through the hole opened at the edge of the membrane. The air, existing inside, exits through the edge of the injector needle, and the cavity is completely filled with autogenic blood. The opened hole can be covered by means of bone wax or tissue adhesive (cyano-acrylate) or fibrin adhesive. Thus, a rigid region, comprising or not comprising dental implant or screw and wherein no soft tissue cell can enter, is formed inside the cavity which is completely filled with autogenic blood.

In the final step, the wound region is covered primarily. It is recommended to realize cutting in the periost in order to free the flap for primary covering. After bone formation, the implant can be placed to the related region, and if the implant is placed in the same step, the recovery heading step can be applied and afterwards, the prosthesis step can be applied. This recovery process duration alters depending on the size of the defect, it may take approximately 6 months or more.

By means of the present invention, blood, which is an autogenic source, is used instead of the graft. Thus, an important cost advantage is provided, and the infection risk and immunologic reaction risk existing in the products obtained from different persons or from different beings are completely eliminated. The application of the present invention, where antibacterial or non-antibacterial membrane is used, to the patient is very easy, and thus an economic application which is comfortable for the patient is realized.