WO2025061620A1 - Ready-made attachment for the reconstruction of bone defects - Google Patents

Abstract

The invention relates to a ready-made attachment for covering and/or reconstructing a bone defect site which has a cavity between the defect surface and the surface of the device facing the bone defect, which cavity can be filled with particulate material, wherein • the attachment is in the form of a thin shell, and • its dimensions and the 3-dimensional geometry of its edges are suitable for covering the most common forms of defect, or • it is a planar shell which can be adapted to cover the most common forms of defect. The invention also relates to a method and to a system for producing the attachment according to the invention.

Description

PREFABRICATED ATTACHMENT FOR RECONSTRUCTION OF BONE DEFECTS

PRIORITY APPLICATIONS

This patent application claims the priorities of the European patent applications

EP 23020434.9, filed on 19.09.2023, EP 24174937.3, filed on 08.05.2024, and

EP 24175774.9 filed on 14.05.2024. The complete disclosure of these European patent applications, the priority of which is claimed herein, is incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. TECHNICAL AREA

The invention relates to a prefabricated attachment for covering and/or reconstructing a bone defect site, which has a cavity that can be filled with a particulate material between the defect surface and the surface of the device facing the bone defect, wherein

• the attachment has the shape of a thin bowl, and

• its dimensions and the 3-dimensional geometry of its edges are suitable for covering the most common defect shapes, or

• it is a planar shell that can be adapted to cover the most common defect shapes,

Another object of the invention is a method for producing the attachment according to the invention.

2. STATE OF THE ART

There is a great need for biomaterials to replace bone tissue and as a guide structure for the growth of new bone in bone surgery in orthopedics, dentistry and other fields to restore bony structures after age-related resorption or loss due to other causes, such as tumor resection, tooth loss, trauma or others.

If there is insufficient bone supply, bone grafting is performed. This can involve raising the alveolar ridge or sinus floor elevation. Bone grafting uses either autologous bone from the same individual or foreign material. The foreign material can be either natural (e.g., donor bone) or synthetic (e.g., some hydroxyapatite products). Bone grafting can be performed either in particulate form or as a block, with the block being square, round, or multi-shaped. In the case of particulate bone grafting, autologous bone can be mixed with foreign material. For example, the following technique is known for raising the alveolar ridge or large lateral deposits while still maintaining sufficient height: A bone block from the same patient is milled out at a donor site (e.g., the angle of the jaw), or appropriate biomaterial is used and transplanted to the desired implantation site. It is then fixed in the local bone either with precise compression without any auxiliary material or with an osteosynthesis screw. In a second procedure, the screw is then removed, if necessary, and the relevant dental implant is inserted. It is also conceivable to insert a dental implant directly and completely into such a bone cylinder on one side.

Various materials can be used for bone augmentation. Either autologous bone or artificial biomaterial, or processed natural biomaterial from xenogeneic or allogeneic bone, are used.

It is known that particulate material or blocks with a pore system heal better than solid material, since solid material requires a long and tedious process of complete dismantling and rebuilding.

It is also known that in blocks with a porous system, the trabeculae cannot be completely replaced with new bone, even if this material is fundamentally resorbable. For these reasons, techniques that predominantly use particulate material are superior to others. However, since mechanical stabilization is necessary in cases of elevated alveolar ridges or large lateral deposits, thin, stable elements are used for this purpose, which enclose the particulate material. These techniques are collectively known as shell techniques, as the thin stabilizing barrier functions like a shell.

This shell technique can be carried out according to the current state of the art using the following techniques that have been known for many years:

• Shelling of an allogeneic cortical bone, whereby the bone is temporarily adapted to the defect by milling.

• Shells of autologous cortical bone which was taken from the same patient and is taken, for example, from the area of the mandibular angle in the mandible or the maxilla (Gellrich, NC, U. Held, R. Schoen, T. Failing, A. Schramm and KH Bormann (2007). "Alveolar zygomatic buttress: A new donor site for limited preimplant augmentation procedures." Journal of Oral & Maxillofacial Surgery 65(2): 275-280.) (Khoury, F (2013). "The bone lid approach in pre-implant and implant surgery: a prospective study." Eur J Oral Implantol 6(4): 375-384).

• Shells made of non-resorbable material (e.g., titanium mesh, metal-reinforced PTFE membranes) that are manually adapted to the defect by bending. Classic examples are the Cytoplast membrane, Goretex membrane, Neoss membrane, and Tiolox membrane.

• Shells made of lactides (Iglhaut technique / Sonic Weid System), which are made malleable by heating and manually adapted to the defect (Iglhaut, G., F. Schwarz, M. Grundel, I. Mihatovic, J. Becker and H. Schliephake (2014). "Shell technique using a rigid resorbable barrier system for localized alveolar ridge augmentation." Clin Oral Implants Res 25(2): el49-154).

A well-known problem is the poor fit of these manually adjusted shells. Furthermore, manual adjustment requires a significant amount of time in the operating room.

European patent application EP 2 536 446 from ReOss proposes a correspondingly customized device, in which surface data of a bone defect is generated from a tomographic image and the defect is virtually cut in a CAD program. This data is used to create a 3D dataset for the production of a shell, which is then used for the shell technique.

International patent application W0201/207808A1 describes customized devices manufactured by 3D printing.

The disadvantage of individual approaches is the high cost of producing each individual shell.

Another problem with many materials is the lack of, non-existent or incomplete absorption.

Collagen, for example, is a readily absorbable material. However, the problem is that collagen softens in the body's aqueous environment.

In the German patent application DE 19 543 110 A1 and the publication Draenert GF et al. (Draenert, GF & Delius, M. The mechanically stable steam sterilization of bone grafts. Biomaterials 28, 1531- 1538 (2007).) a technique is described in which native bone material after prior Drying is followed by steam sterilization. The resulting bone material exhibits the strength and elasticity of natural, untreated bone of the same type and origin.

The object of the present invention was to provide an adaptable attachment for covering and/or reconstructing a bone defect site, which does not have the disadvantages of the previously known devices or only has them to a reduced extent and therefore offers not only individual defect adaptability but also biologically meaningful resorbability, without, however, losing the mechanical rigidity for bony healing.

BRIEF SUMMARY OF THE INVENTION

This object was achieved according to the invention by providing a prefabricated attachment for covering and/or reconstructing a bone defect site, which has a cavity that can be filled with a particulate material between the defect surface and the surface of the attachment facing the bone defect, wherein

• the attachment has the shape of a thin shell, with one surface facing away from the bone defect and one surface facing the bone defect, and

• its dimensions and the 3-dimensional geometry of its edges are suitable for covering the most common defect shapes, or

• it is a planar shell which is adaptable to cover the most common defect shapes, wherein the attachment comprises a rigid material made from a resorbable starting material, in particular from an animal epidermis.

Another object of the invention is a method for producing an attachment according to the invention for a device for covering and/or reconstructing a bone defect site from biomaterial, the method comprising the following steps:

(a) Rough cleaning of the resorbable starting material, preferably an animal epidermis;

(b) if necessary, cutting the cleaned starting material, preferably an animal cuticle;

(c) treating the thus obtained roughly cleaned and optionally trimmed starting material, preferably an animal cuticle, with one or more degreasing chemicals;

(d) supplying energy to the defatted and, if necessary, cut starting material, preferably an animal skin, to a temperature of 50 to 300 °C on a shaping base, if necessary covered with a suitable overlay, the sizes and geometries of which correspond to one of the most frequently occurring defect forms, (e) where appropriate, removing any material extending beyond the support.

The article according to the invention is preferably manufactured according to the following process, wherein:

• in step (a) the resorbable starting material is preferably produced from a collagen-containing material such as, for example, from the skin of an animal, in particular from an animal epidermis of a mammal or a human, in particular from bovine epidermis.

• in steps (c) and (d), the starting material, preferably an animal cuticle, is immersed in a degreasing liquid after appropriate pre-cleaning and pre-fermentation, preferably in a degreasing liquid such as acetone, which, upon energy input, leads to a uniform and immediate release of energy in the impregnated starting material, preferably in the impregnated animal cuticle. In the case of acetone, this particular effect appears to be enhanced by the fact that, in the presence of oxygen, traces of acetone peroxides are formed, which are highly explosive.

• This involves a strong denaturation of the starting material, especially a collagen-containing material such as animal skin, without leading to combustion or charring. Therefore, microwaves are preferred, as they allow for a particularly well-distributed and rapid energy release.

The invention further relates to a system for producing an attachment according to the invention for covering and/or reconstructing a bone defect, comprising the following components:

(I) one or more shaping supports whose sizes and geometries correspond to those of the most frequently occurring defect shapes;

(II) if necessary, one or more shaping supports complementary to the respective support (I), the sizes and geometries of which correspond to those of the most frequently occurring defect shapes;

(III) a sealable apparatus suitable for receiving (I) for supplying thermal energy;

(IV) if necessary, a packaging unit connected thereto in which the attachment manufactured in components (I) to (III) can be packaged under sterile conditions. SHORT DESCRIPTION OF THE DRAWING

Fig. 1 shows a schematic representation of the preferred shapes of the attachment according to the invention as U-shape (a) or J-shape (b).

Fig. 2 shows a microscopic image of the material of the attachment according to the invention:

A: Bovine epidermis after fermentation and before preparation without microwave treatment;

B: the material from A after microwave treatment.

DETAILED DESCRIPTION OF THE INVENTION

According to this invention, a resorbable attachment for use in a surgical bone augmentation technique with thin stabilizing walls (shells) to improve bone healing of defects and/or osseointegration of implants is provided. The attachment is treated with an anti-hydration treatment and pre-shaped in a J-shape or U-shape for semi-plastic adaptation to the defect from a resorbable starting material, in particular an animal epidermis. In certain cases, for example, with smaller bone defects, a completely planar shape can also be used, which can then be manually reshaped during fixation. This reshaping is performed analogously to the Khoury method (cf. Khoury F, Khoury CH. Mandibular bone block grafts: diagnosis, instrumentation, harvesting techniques and surgical procedures. In: Khoury F, Antoun, H, Missika P, editors. Bone Augmentation in Oral Implantology. Berlin: Quintessence, 2007.).

The term "cap" as used above and below refers to a suitable device for covering and/or reconstructing a bone defect. Its edges are made of a resorbable biomaterial ("biomaterial shell"), whose edges are defined by the dimensions of a bone defect. The three-dimensional shape of the cap generally corresponds to the desired bone structure and serves as a shell for the particulate material until it fully ossifies and thus becomes dimensionally stable.

The term "resorbable starting material" as used above and below encompasses natural, resorbable biomaterials. Natural substances used as resorbable starting materials include collagen-containing materials such as autologous or allogenic bone, skin, or coral. Other examples include collagen, chitosan, which is derived from chitin, and alginate, which is derived from seaweed. Starting materials containing collagen are particularly preferred. Collagens are a group of structural proteins (proteins that form a bundle of fibers) found primarily in connective tissue, found only in multicellular animals (including humans). Collagens are found, among other things, in the white, inelastic fibers of tendons, ligaments, bones, and cartilage. Layers of the skin (epidermis and subcutaneous tissue) are also composed of collagens.

The collagen material used to produce the attachment according to the invention can be mammalian skin, including humans, particularly autogenous or allogeneic human skin. The skin of farm animals such as cattle, sheep, pigs, horses, or other suitable donor species is preferred. This makes the resulting attachment resorbable and does not require further removal.

Those skilled in the art are familiar with the rough cleaning of hides, for example, from leather production (see www.lederpedia.de). After washing the collagen-containing natural product, preferably hide, to remove dirt, dung, blood, and possibly preservative salt, the hair is removed in a liming process. After dehairing, the subcutaneous connective tissue (flesh and fat) is mechanically scraped off by fleshing. Thicker cattle hides can be split horizontally into two pieces. Both the upper part of the hide, the grain gap, and the lower flesh gap can be used to produce the attachment according to the invention; the grain gap is preferably used. The thickness of the hide can be adjusted to the millimeter.

Chitosan (is a naturally occurring biopolymer derived from chitin and, like chitin, is a polyaminosaccharide. Chitosan is produced by deacetylation.

Alginic acid, also known as algin, is produced by brown algae and some bacteria (e.g., Azotobacter). In algae, it is the structural element of cell walls. The intercellular gel matrix gives the algae both flexibility and strength. Algin is a byproduct of the wet extraction of iodine from marine algae. The salts of alginic acid are commonly referred to as alginates.

For 3D shaping, there are preferably two prefabricated 3D shapes, depending on the most common defect shapes: U-shape and J-shape. For a vertical defect, the U-shape is selected and placed on the defect like a raised hat, preferably with screws, preferably osteosynthesis screws. For lateral ridge defects, the J-shape is selected to replace the lost side of the alveolar ridge wall. This is preferably also secured with osteosynthesis screws. It is also possible to use essentially planar shapes, which are manually adjusted before being secured to the defect.

In the method according to the invention, preferably native collagen, in particular skin tissue, is subjected to dry heating after removal of any adhering tissue, in particular fatty tissue, for example, subcutaneous fat in the case of epidermal material. Any remaining protein is denatured and the tissue material is freed of moisture, in particular natural moisture. Drying is generally carried out to a moisture content below 10%, in particular below 5%, relative humidity. The exposure of tissue material dried in this way to an aqueous environment can then no longer adversely affect its mechanical properties.

Drying can be carried out at temperatures above the denaturation temperature of proteins (approx. 40°C) and temperatures below the decomposition temperature of type I collagen (approx. 300°C). Drying is generally carried out at temperatures between 50°C and 300°C, with temperatures below 250°C being preferred. If the drying temperatures are above 100°C, especially above 120°C, the tissue material is already largely sterile. It can then be stored temporarily between drying and sterilization. If drying takes place in the range between the denaturation temperature for proteins (42°C) and approximately 100 or 120°C, then intermediate storage under refrigeration, especially in the freezer, is required if desired. The higher the drying temperature, the shorter the drying time.

Dry heating as preparation for sterilization can be performed in ambient air or under ambient pressure. Electrically heated ovens with an appropriate air temperature are suitable for dry heating. Dry heating with microwave irradiation is also suitable.

Adhering foreign matter, such as connective tissue, fatty tissue, and other tissues, is preferably removed mechanically. If necessary or desired, further cleaning can then be carried out by washing and/or extracting the skin material. Suitable solvents for this purpose are water-miscible solvents, particularly alcohols such as ethanol or isopropanol, ketones such as acetone or butan-2-one, or esters such as ethyl acetate, or mixtures thereof. Adhering blood residues and fat can be effectively removed during such further cleaning. At the same time, partial dehydration takes place. During the heat treatment described, shrinkage may occur, which must be taken into account in relation to the desired size of the material.

In this case, a special collagen material is used, which is best obtained from thick epidermis.

Preferably, the heating in step (d) leads to a uniform, immediate release of energy in the tissue through the immediate evaporation of the liquid, which has degreasing properties. The combination of a rapid, effective energy input into the material with a low-boiling, or even better, energy-releasing, degreasing liquid results in the appropriate product properties. One example of this is the use of microwaves and acetone. The rapid, deep delivery of energy by the microwaves enables an explosive decomposition of the acetone, possibly also with the assistance of acetone peroxides, which can be formed from acetone in the presence of oxygen and decompose explosively upon application of energy.

The material obtained in this way shows reduced softening and long-lasting stiffness.

Further preferred embodiments of the attachment according to the invention are those in which

(i) the rigid material exhibits reduced softening in an aqueous environment.

(ii) the rigid material is obtained by heat denaturation of collagen.

(iii) the starting material, in particular the animal skin with reduced water absorption capacity, is obtainable by degreasing and heating in the absence of moisture.

Preferably, resorbable purified, defatted animal skins are used, such as those used for leather production or for the production of soft membranes such as Bio-Gide® from Geistlich Vertriebsgesellschaft mbH Baden-Baden, Germany.

(iv) the attachment is planar or has a U- or J-shape.

(v) the attachment is a thin shell with a thickness of 0.3-4.0 mm, preferably 1.0-2.0 mm.

(vi) the attachment has a length of 5-50 mm, preferably 10-30 mm.

(vii) the attachment has a width before 3D bending of 10-40 mm, preferably 10-30 mm. (viii) the attachment additionally has one or more fastening elements.

Preferably, the material of the attachment according to the invention contains cavities connected to form a pore system into which the body's own cells can grow.

Further preferred embodiments of the method for producing the attachment according to the invention are those in which

(ix) in step (b), the shrinkage occurring during the heat treatment is taken into account in relation to the final size of the attachment to be achieved, so that the execution of step (e) can be omitted.

(x) the degreasing chemical in step (c) is acetone.

(xi) the supply of energy in step (d) is carried out by irradiating microwaves, preferably in a microwave oven.

An alternative embodiment of the method according to the invention comprises the following steps:

(xii) the starting material, in particular the animal skin, is treated directly with one or more degreasing chemicals, preferably acetone, after the rough cleaning,

(xiii) the starting material thus obtained, in particular the animal epidermis thus obtained, is brought to a temperature of 50 to 300 °C by supplying energy, preferably by microwaves, on a shaping base, optionally covered with a suitable overlay whose sizes and geometries correspond to one of the most frequently occurring defect forms, and

(xiv) any material extending beyond the support shall be removed.

The removal of the material projecting beyond the support in step (iii) is carried out by suitable cutting, in particular in a cutting die provided for this purpose.

The following examples are intended to illustrate the invention without limiting it.

Example 1:

A product according to the invention is based on a bovine epidermis, which has been pre-cleaned in a similar way to other biomaterials of the same origin. The 2D material is then cut to size the desired final size of the subsequent attachment. This takes into account shrinkage during treatment with the degreasing chemical and the energy input. The material is then immersed in pure acetone. The acetone is then changed if necessary, depending on the material's water content, until the maximum possible dehydration and saturation with acetone is reached. The sample is then placed on a microwaveable mold made of heat-resistant material that is not affected by acetone and clamped in place. The mold consists of a female and a male mold, with the shell material, moistened with acetone, being inserted between the two parts. Both parts are mechanically secured to one another by screwing to prevent deformation during the curing and drying process. The finished molding apparatus with the shell material is then placed in a microwave oven at a power output of 400W-1000W for a time of 10 seconds to 300 seconds, depending on the energy setting and material dimensions. The resulting 3D shell material is removed from the mold, packaged, and sterilized by radiation or other means.

A microscopic image of the resulting material is shown in Fig. 2B. The cavities connected to form a pore system are clearly visible:

Fig. 2A: Bovine epidermis after fermentation and before preparation without microwave treatment; Fig. 2B: the material from A after microwave treatment.

Example 2:

A product according to the invention is based on bovine epidermis, which has been pre-cleaned similarly to other biomaterials of the same origin. The material is then immersed in pure acetone. The acetone is then changed if necessary, depending on the water content of the material, until the maximum possible dehydration and saturation with acetone is reached. The sample is then placed on a microwaveable mold made of heat-resistant, acetone-resistant material and clamped there. The mold consists of a female and a male mold, with the shell material moistened with acetone being inserted between the two parts. Both parts are mechanically secured to each other by screwing to prevent deformation during the curing and drying process. The finished mold apparatus with the shell material is then placed in a microwave and subjected to a power supply of 400W-1000W for a time of 10 seconds to 300 seconds, depending on the power setting and material dimensions.

The resulting 3D shell material is removed from the mold and placed into a cutting mold, which then forms the resulting curved blank of the attachment with a specified shape and trims the edges to the specified dimensions. The finished attachment is then packaged and sterilized by radiation or other means. Example 3:

A product according to the invention is based on a pre-cleaned, collagen-containing biomaterial that has been molded into a flat membrane mold and shaped. The material is then immersed in pure acetone. The acetone is then changed if necessary, depending on the material's water content, until maximum dehydration and saturation with acetone are reached. The sample is then placed on a microwaveable mold made of heat-resistant, acetone-resistant material and clamped there. The mold consists of a matrix and a patrix, with the acetone-moist shell material inserted between the two parts. Both parts are mechanically secured to each other by screwing to prevent deformation during the curing and drying process. The finished mold apparatus with the applied shell material is then placed in a microwave and subjected to a power supply of 400W-1000W for a time of 10sec to 300sec, depending on the power setting and material dimensions. The resulting 3D shell material is removed from the mold and placed into a cutting mold, which then forms the resulting curved blank of the attachment with a specified shape and trims the edges to the specified dimensions. The finished attachment is then packaged and sterilized by radiation or other means.

While particular embodiments of the invention have been shown and described, it will be apparent to those skilled in the art that changes and modifications may be made therein without departing from the invention in its broader aspects. Therefore, it is the intention of the appended claims to cover all such changes and modifications that fall within the true spirit and scope of the invention.

Claims

PATENT CLAIMS 1. Prefabricated attachment for covering and/or reconstructing a bone defect site, which has a cavity that can be filled with a particulate material between the defect surface and the surface of the attachment facing the bone defect, wherein • the attachment has the shape of a thin shell, with one surface facing away from the bone defect and one surface facing the bone defect, and • its dimensions and the 3-dimensional geometry of its edges are suitable for covering the most common defect shapes, or • it is a planar shell which is adaptable to cover the most common defect shapes, characterized in that the attachment comprises a rigid material obtainable from a resorbable starting material. 2. Attachment according to claim 1, characterized in that the rigid material has a reduced softening in an aqueous environment. 3. Attachment according to claim 1 or 2, characterized in that the rigid material is obtainable by heat denaturation of collagen. 4. Attachment according to one of claims 1 to 3, characterized in that the starting material is a material obtainable from an animal epidermis. 5. Attachment according to one of claims 1 to 4, characterized in that it is planar, or its 3-dimensional geometry has a U- or J-shape. 6 Attachment according to one of claims 1 to 5, characterized in that the material is obtainable by thermal treatment of a resorbable starting material with one or more degreasing chemicals and an input of energy to a temperature between 50°C and 300°C. 7. Attachment according to one of claims 1 to 6, characterized in that the material is obtainable by thermal treatment of a resorbable starting material with acetone and a supply of energy in the form of microwaves. 8. Attachment according to one of claims 1 to 7, characterized in that the material has cavities connected to form a pore system. 9. Attachment according to one of claims 1 to 8, characterized in that the thickness of the thin shell is 0.5 to 4.0 mm, preferably 1.0 to 2.0 mm. 10. Attachment according to one of claims 1 to 9, characterized in that the thin shell has a length of 5 to 50 mm, preferably 10 to 30 mm. 11. Attachment according to one of claims 1 to 10, characterized in that the thin shell has a width of 10 to 40 mm, preferably 10 to 30 mm, before 3D bending. 12. Attachment according to one of claims 1 to 11, characterized in that it is obtainable from a resorbable starting material by the following steps: (a) Rough cleaning of the starting material; (b) where appropriate, cutting the cleaned starting material; (c) treating the thus obtained roughly cleaned and optionally cut starting material with one or more degreasing chemicals, preferably acetone; (d) supplying energy to the degreased and, if necessary, cut starting material to a temperature of 50 to 300 °C on a shaping base, preferably by microwaves, if necessary covered with a suitable support, the sizes and geometries of which correspond to one of the most frequently occurring defect shapes, (e) where appropriate, removing any material extending beyond the support. 13. A method for producing an attachment for covering and/or reconstructing a bone defect site according to one or more of claims 1 to 12, comprising the following Steps: (a) Rough purification of a resorbable starting material; (b) where appropriate, cutting the purified starting material; (c) treating the thus obtained roughly cleaned and optionally cut starting material with one or more degreasing chemicals; (d) supplying energy to the defatted and, if necessary, cut biomaterial to a temperature of 50 to 300 °C on a shaping base, if necessary covered with a suitable overlay, the size and geometry of which correspond to one of the most frequently occurring defect forms, (e) where appropriate, removing any material extending beyond the support. 14. The method according to claim 13, wherein the resorbable starting material is a collagen-containing material, preferably an animal epidermis. 15. The method according to claim 13 or 14, wherein in steps (c) and (d) acetone is used as the degreasing liquid and the energy is supplied by microwaves. 16. System for producing an attachment for covering and/or reconstructing a bone defect site according to one of claims 1 to 12, comprising the following components: (I) one or more shaping supports whose sizes and geometries correspond to those of the most frequently occurring defect shapes; (II) if appropriate, one or more shaping supports complementary to the support (I), the sizes and geometries of which correspond to those of the most frequently occurring defect shapes; (III) a sealable apparatus suitable for receiving (I) for supplying thermal energy, preferably a microwave oven; (IV) if necessary, a packaging unit connected to it in which the attachment produced using components (I) to (III) can be packaged under sterile conditions.