DE19805673A1 - Production of injectable bone replacement and augmentation material that hardens at site of application - Google Patents

Abstract

Production of a bone replacement and augmentation material of particles embedded in a homogeneous matrix comprises mixing bioabsorbable particles with a biodegradable matrix material to form a flowable workable mixture that hardens at the site of application. An Independent claim is also included for a kit for producing a bone replacement and augmentation material as above, comprising the particles, the matrix material, an applicator for delivering the mixture to the site of application, a mixer connected to the applicator, and means for supplying the particles and matrix material to the mixer.

Description

The invention relates to a method for producing a kno Chen replacement and augmentation material, in which in the appli graced state particles of a certain dimension in a Matrix embedded. Furthermore concerns the Erfin a kit for the production of a bone replacement and augmenta tion material according to this process, which the necessary Starting materials and an application unit comprises.

The biocompatible manufactured according to the invention Bone replacement material can be used as a material for filling kno Defects in periodontology and for bone augmentation can be used in dental implantology. It is also as a material for filling bone defects in the Surgery can be used.  

The material you are looking for must be biologically compatible. H. in no immunogenic or continued inflammatory response in vivo induce. Its physical structure must be infiltration of cells and there must be a resorption time in vivo feature that is suitable for this function. In addition, a such material be good initial mechanical stability to sit. It would also be desirable that such a material in the application and modeling of the Be is easy to use.

For such a material there is surgery, in which Periodontology and dental implantology a big one Desire. The previous techniques and materials have been removed which is complicated to use, or the material has - ge long-term - not the desired properties.

For bone regeneration in periodontology and bone new formation in dental implantology is in addition to the Use of membranes (GTR and GBR) or autologous bones Bone replacement material as a placeholder for new bone formation applied.

The membranes that prevent epithelial migration into the defect are without the additional use of bones or bone replacement materials are often unable to support the ur originally created space up to complete bone rain to keep generation or new formation free, since the membranes do not have sufficient mechanical stability. Besides, that is Application of the membrane is a very complex technique and with a relatively high complication rate such as membrane exposure and Suture dehiscence afflicted.

There are basically four different types of Im plantation materials for filling bone defects (Kohal, R.-J., ZM 87, No. 10, 1997, pp. 56-61). Autologist (Autogenous) materials come from the same organism, ho molge (allogeneic) materials are used by other individuals obtained from the same species, heterologous (xenogeneic) materials are from individuals of another species (for example: bo  viner bone). Alloplastic materials are synthetic Manufactured materials (hydroxyapatite, bio glasses).

Autologous bone is the optimal material for filling Bone defects and for augmentation. An immunolo reaction is impossible. The car also has lied bones a certain osteogenetic potential. The Ver However, the use of autologous bone often reaches the limit the sufficient availability and is also problematic tic of a second intervention for the removal.

The allogeneic bone comes from individuals of the same species, but different genetic makeup. The alloge Bones are classified as demineralized or mineralized freeze-dried bone offered. When using this Er is a transmission of infectious diseases not excluded. Furthermore, this can be genetically foreign Material may trigger local immune reactions.

Xenogenic materials are made from bovine bones, for example (BioOss®, biomaterials Geistlich) or corals (Interpore 200®, Interpore International). It is a matter of Calcium phosphate preparations because of the bovine bone or Die Koral len completely freed from all organic components become. The disadvantage of these preparations is the lack of knots inductance and a very slow re sorption (1 to 5 years).

Hydroxylapa can be found as alloplastic bone replacement materials tit and tricalcium phosphate application. Hydroxyapatite is not and tricalcium phosphate is very slowly absorbable. Because of the inadequate biodegradability is a complete In tegration in the newly formed bones not reached.

The invention is therefore based on the problem of a biological compatible material for bone augmentation and opening to provide bone defect filling that the Infiltration of cells allows a good initial mechani  cal stability and simple, easy to use Way can be applied.

To solve this problem, the method according to the invention ren of the type mentioned that the method the mixing of bioabsorbable particles certain size with an inatrixbil embedding the particles also biodegradable mass to a flowable higen, soft processable material, the mass on Application site hardens and thereby the bone replacement and eye mentation material.

This makes a biocompatible bone replacement and Augmentation material provided that as a composite consists of 2 parts. The first part is a liquid ma Trix-forming mass, which after mixing with the particles should harden. After curing, the mass has a shape stability, is biologically well tolerated and becomes absorbed by the surrounding tissue for a certain time. Of the second part of the composite consists of filling particles, each according to the degree of addition in the material the desired consi lend strength and improve shape stability. This one part is also absorbable.

A bone defect is filled in or closed with the material augmenting area built. After a certain time the entire material is absorbed, making room for newly formed bone that occupies the appropriate space.

By suitable selection of the particle size and the particle density The consistency during application can be in the matrix and optimized the mechanical stability after curing become. These values may vary depending on the application you want can be easily determined experimentally. The volume fraction of the Particles in the total mixture can be between 10 and Make up 70 vol .-%, preferably between 20 and 50 vol .-%. The particles are preferably smaller than 0.5 mm around the To ensure fluidity of the mixture during processing  Afford. A mean diameter is more preferred Particles between 0.1 and 0.3 mm are provided.

Since the material produced with the method according to the invention al after the mixing process and before curing a liquid to pasty consistency, the viscosity of which is determined by the men The proportion of solid particles can be controlled, the material can easily applied and modeled.

The solid, but bioabsorbable particles that the Composite greater strength and moldable consistency should lend, for example, consist of collages. Collagen is the main protein of the bone. Purified colla gene whose antigenic components (telopeptides) have been removed, has good biocompatibility. It will depend on the Her Notification procedure after 4 weeks at the earliest after 6 Months absorbed. Because of its microstructure, it is too well suited for taking up and protracted delivery of effective substances such as antibiotics or bone growth factors.

Alternatively, the filler particles could also come from another fe most biologically compatible material or z. B. a biolo cally degradable plastic. For example, for this purpose the use of Polyglactin 910 (Vicryl®) is possible Lich. Polyglactin is a copolymer consisting of glycolide and Lactide. The material has so far been in the most diverse Im implant forms, for plates, screws, stents, nets, foils and sutures successfully proven. After about 2 to 4 weeks the hydrolytic degradation of the substance begins. She'll be back free standing in the body's own breakdown products (lactic acid) A foreign body load and immunological or infectious serious side effects can therefore be excluded.

The matrix-forming mass should be viscous at the time of application be liquid and then harden at the application site. As for this mass of suitable material comes for example fibrinkle about in question, within the inventive method can be produced by mixing two components and which then cures to form a fibrin network. After  the fibrin network shows sufficient tear when hardened stability and volume stability. It is biocompatible and through fibrinolysis completely degradable. It poses a bad thing ten breeding ground for bacteria, so that the application of Fi Brinkleber does not increase the risk of wound infection. The fibrin stars form guide rails for the sprouting of vascular material granulation tissue rich in fibroblasts.

Alternatively, a biodegradable 2-component Plastic are used.

The use of 2 components is not mandatory, insofar as one Prevent the hardenable mass from hardening too early can be changed. For example, plastics would be considered here bar, which are stored in the dark and harden under the influence of light Another biologically compatible material for the matrix-forming mass could be methyl cellulose.

In a development of the invention it is provided that the material the particles and the material of the matrix-forming mass be chosen that one of the two materials clearly biodegrades faster than the other.

Due to different absorption rates of matrix and particles form voids in the material so that on the one hand osteoblasts in the material for new bone formation immigrate, on the other hand during this new bone the modeled form of the bone replacement material still remains.

To achieve this, for example, in the event that the matrix-forming mass consists of fibrin glue, the Fi brine glue, preferably a fibrinolysis inhibitor, d. H. an anti fibrinolytic such as B. aprotinin, are added. The fibri This will nolytically degrade the solidified fibrin glue delayed. By the concentration of the fibrinoly used seinhibitors can set the optimal degradation speed become.  

In a development of the invention, the material of the particles or additional matrix-forming mass before processing Substances with pharmacological and / or bone inductive Effect are added, such as. B. antibiotics or bone morphogenetic proteins (BMP). In the event that the particles consist of collagen, it is advantageous to use this effective sub like antibiotics or bone growth factors Add collagen because of its microstructure Recording and protracted release of active substances are suitable is not.

The method according to the invention can also be used in Kombina tion with known membrane techniques, such as the guided tissue right generation (GTR) or guided bone regeneration (GBR) become.

Furthermore, to achieve the object of the invention, a kit for Production of a bone replacement and augmentation material provided according to the inventive method, which the biodegradable particles, the starting material for the manufacture position of the matrix-forming mass, and an application unit for the implementation of the procedure and simultaneous application adorn the forming bone replacement and augmentation mat rials includes. The application unit consists of one Applicator for feeding the finished mixed material to the Application site, a mixing device upstream of the applicator direction for mixing the particles with the matrix-forming mas se, and means for feeding the particles and the matrix form the mass to the mixing device.

An advantage of the method according to the invention is that the bone replacement and augmentation material in a simple way can be prepared by mixing certain components. The kit according to the invention increases the manageability of the process rens in addition and enables the Ver drive under reproducible conditions with sufficient Si safety also in individual practices, for example dental Practices can be applied. For this, the application unit from a double syringe provided with a mixing tip  stand. The components for the matrix forming mass and the Particles can be placed in the syringe and stored. If the matrix-forming mass consists of a 2-component system exists, it is possible, for example, that a component for the matrix-forming mass in one syringe of the double syringe and the other component with the already mixed parts hold in the other syringe. During the spraying gangs the components mix when flowing through a Mixing cannula, so that after application of the curing process puts.

The advantages of the invention will become clearer from the drawing with FIGS. 1 to 3. It shows examples in dental periodontology and implantology without the application of the invention being restricted to this.

In the drawing shows

• - Figure 1 is the use according to the method Augmen obtained tationsmaterials in periodontal therapy;.
• - Figure 2 is the use of the augmentation material in dental implantology.
• - 3, an application unit for performing the method Fig.

Fig. 1 shows in longitudinal section under Fig. A a bone ( 1 ) next to an incisor. The situation is shown after removal of the granulation tissue and the pocket epithelium and after the root planing. As shown under B, the defect heals without further measures in the sense of a repair without new bone formation. An epithelial attachment is formed ( 2 ). However, if the defect is filled out as shown under C with the augmentation material ( 3 ) obtained by the procedure, with the mucoperiosteal flap fixed above it, as can be seen under E, there is a real regeneration of desmodont and bone ( 5 ). The course of the regeneration according to the GTR method known in the prior art with the aid of a membrane ( 4 ) is shown comparatively in FIG.

Fig. 2 shows the use of the augmentation material in dental implantology. Fig. A shows the case that after insertion of an implant several threads are exposed due to insufficient bone availability ( 1 ). Filling the bone defect with the augmentation material ( 2 ) obtainable by the method and wound closure lead to the situation shown under B. This induces new bone formation in the augmentation area at position ( 3 ).

Fig. 3 shows an application unit for performing the method with a 2-component system. The ready-to-use application unit consists of a syringe 1 which contains a component of a matrix-forming mass, a syringe 2 which contains a second component for the matrix-binding mass and the particles, and a mixing cannula 4 in which all components are brought together. The syringes 1 and 2 are held together in a holder 3 .

The application unit works as already described above, is easy to use and allows a sufficiently intense Mixing of the components at the time of application so that the bone replacement or augmentation material in situ Application site forms.

Of course, others are also within the scope of the invention Bone defect treatments possible. An application of the with the Process available material would come, for. B. in splinter breaks considered or in casualty surgery to cement others Defects.

Claims (13)

1. A method for producing a bone replacement and Augmenta tion material, in which, in the applied state, particles of a specific dimension are embedded in a homogeneous matrix, characterized in that the method comprises the mixing of bioabsorbable particles of a specific size with a matrix-embedding particle also includes biodegradable mass to a flowable, soft processable material, the mass hardens at the application site and thereby forms the solid bone substitute and augmentation material. 2. The method according to claim 1, characterized in that the Volume fraction of the particles in the total mixture about 10 to 70%, preferably between 20 and 50%.   3. The method according to claim 1 or 2, characterized in that the particles have an average diameter of less than 0.5 mm, preferably between 0.1 and 0.3 mm. 4. The method according to one of claims 1 to 3, characterized records that the particles from collagen, preferably cleaned telopeptides-free collagen, or a biological degradable plastic. 5. The method according to any one of claims 1 to 4, characterized shows that the matrix-forming mass consists of at least 2 components that can be stored in liquid form are available by mixing. 6. The method according to any one of claims 1 to 5, characterized records that the matrix-forming mass of fibrin glue or is a biodegradable 2-component plastic. 7. The method according to any one of claims 1 to 5, characterized records that the material of the particles and the material of the matrix-forming mass can be selected so that one of the at the materials biodegrade significantly faster than the other. 8. The method according to claim 7, characterized in that the Particles consist of collagen and the matrix-forming mass Fibrin glue exists, the fibrin glue preferably being a Fibrinolysis inhibitors (antifibrinolytic, e.g. aprotinin) will. 9. The method according to any one of claims 1 to 8, characterized records that the material of the particles or the matrix form the mass before processing additional substances with phar macological and / or bone inductive effect added be, e.g. B. antibiotics or bone morphogenetic proteins (BMP). 10. The method according to any one of claims 1 to 9, characterized ge indicates that it is used in combination with membrane techniques, such as  guided tissue regeneration (GTR) or guided bone regeneration (GBR) is used. 11. Kit for producing a bone replacement and augmentation material by the method according to claims 1 to 10, which comprises:

• - the biodegradable particles,
• - The starting material for the production of the matrix-forming mass, and
• - An application unit for carrying out the method according to one of claims 1 to 10 and simultaneous application of the bone replacement and augmentation material formed consisting of:
  • - An applicator for feeding the mixed material to the application site
  • a mixing device upstream of the applicator for mixing the particles with the matrix-forming mass,
  • - Means for feeding the particles and the matrix-forming mass, possibly in the form of several components, to the mixing device.

12. Kit according to claim 11, characterized in that the Ap plication unit from a double provided with a mixing cannula syringe exists. 13. Kit according to claim 12, characterized in that the off gear materials, d. H. the particles and the components for the Matrix-forming mass in the syringes.