RU2721873C1 - Allogenic combined bone graft for treating complex fractures of the proximal humerus, a method for preparing it - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: group of inventions relates to medicine. Combined bone allogenic graft for treating complex fractures of the proximal humerus comprises a non-demineralised bone block derived from a donor bone, which is a fibular fragment with length of 6–8 cm, including a head, a neck and a part of the diaphysis, equipped along the whole surface through channels, made with diameter of not more than 2 mm, located at 3–5 mm from each other, wherein the holes of the bone block are filled with human collagen 1 in the form of a sponge with a fine cell structure. Method for producing a combined bone allogenic graft comprises formation of a fragment from a donor fibula frozen at a temperature of -40 °C, the fragment contains a head with a neck and a part of the diaphysis with a total length of 6–8 cm, when forming the fragment, the periosteum, cartilage and soft tissue remains are removed, after which through the entire surface of the fragment, through holes with diameter of not more than 2 mm are formed at distance of 3–5 mm from each other, followed by its dehydration, degreasing and drying, after which the obtained perforated bone block is impregnated with human collagen 1 solution with subsequent lyophilization under conditions providing conversion of collagen solution into a sponge with fine-mesh structure throughout the bone block.EFFECT: inventions provide strengthening of the proximal humerus in the surgical management of complex osteochondral fractures of the shoulder accompanied by bone deficit, and creation of conditions for facilitating reduction of fragments and healing of the fracture.6 cl, 2 ex, 11 dwg

Description

FIELD OF THE INVENTION

The invention relates to medicine, in particular to traumatology and orthopedics, and can be used in the surgical treatment of patients with complex fractures of the proximal humerus, accompanied by bone deficiency.

State of the art

The most severe, multi-fragmented proximal humerus fractures usually develop in older people with poor bone quality. It is extremely difficult to reposition and retain fragments with traditional metal fixators during such fractures. Natural complications are nonunion of the fracture or improper adhesion of the fracture as a result of unsuccessful reposition, or secondary displacement [Jung S.W. et al. Factors that influence reduction loss in proximal humerus fracture surgery // Journal of orthopedic trauma. - 2015. - T. 29. - No. 6. - C. 276-282.]. A possible treatment option is anatomical arthroplasty of the shoulder joint. The functional outcome of such operations is rarely satisfactory, as To restore the function of the hand, fixation of the large and small tubercles is necessary, and they, with poor bone quality, are usually destroyed and cannot be fixed. Arthroplasty of the shoulder joint is possible with a reversible design, but a large number of complications with such arthroplasty in the acute period of trauma are noted in the publications. [Zumstein M.A. et al. Problems, complications, reoperations, and revisions in reverse total shoulder arthroplasty: a systematic review // Journal of shoulder and elbow surgery. - 2011. - T. 20. - No. 1. - P. 146-157.]. [Anakwenze O.A. et al. Reverse shoulder arthroplasty for acute proximal humerus fractures: a systematic review // Journal of shoulder and elbow surgery. - 2014. - T. 23. - No. 4. - P. 73-80]. To fix multi-fragmented fractures of the proximal humerus, it is customary to use specialized metal plates with screws locking in them. However, with poor bone quality, complications such as eruption of screws, improper adhesion with varus deformation, migration of screws with unscrewing them from the plate develop [Launonen A.P. et al. Treatment of proximal humerus fractures in the elderly: a systematic review of 409 patients // Acta orthopedic. - 2015. - T. 86. - No. 3. - P. 280-285.] [Haasters F. et al. Complications of locked plating for proximal humeral fractures - are we getting any better? // Journal of shoulder and elbow surgery. - 2016. - T. 25. - No. 10. - P. .. 295-303 .; Biermann N. et al. Augmentation of plate osteosynthesis for proximal humeral fractures: a systematic review of current biomechanical and clinical studies // Archives of orthopedic and trauma surgery. - 2019. - P. 1-25.]. To prevent these complications, it is necessary to strengthen the bone destruction zone. For this purpose, the humeral head is augmented with methyl methacrylate cement. The disadvantage of this solution is the heating of the cement during the polymerization to significant temperatures. In addition, cement is toxic, which can lead to the development of bone cement implantation syndrome, and does not degrade in the body [Schliemann B. et al. Screw augmentation reduces motion at the bone-implant interface: a biomechanical study of locking plate fixation of proximal humeral fractures // Journal of shoulder and elbow surgery. - 2015. - T. 24. - No. 12. - P. 1968-1973; Hines C. B. Understanding Bone Cement Implantation Syndrome // AANA Journal. - 2018. - T. 86. - No. 6.].

Bone grafts used to strengthen the fracture area are known in the art. They are non-toxic and degrade over time. [Cha N. et al. Treatment of comminuted proximal humeral fractures using locking plate with strut allograft // Journal of shoulder and elbow surgery. - 2017. - T. 26. - No. 5. - C 781-785. http://dx.doi.org/10.1016/j.jse.2016.09.0955]. It is known to use a cryopreserved allogeneic transplant from the tubular part of the fibula, ulna or radius, which strengthens the fracture zone in complex fractures of the proximal humerus. [Hinds R.M. et al. Geriatric proximal humeral fracture patients show similar clinical outcomes to non-geriatric patients after osteosynthesis with endosteal fibular strut allograft augmentation // Journal of shoulder and elbow surgery. - 2015. - T. 24. - No. 6. - C. 889-896.]. The disadvantages of such transplants include the cylindrical shape, which does not ensure the stability of its position in the fracture zone - the transplant can fall into the bone marrow canal of the humerus, which requires additional techniques and means of holding it until the fracture is fixed. Such transplants have almost no osteoconductive effect, as they consist of the tubular part of the bone. The graft also cannot be used as a carrier of biologically active substances. In addition, the grafts are stored frozen in special equipment, the graft is thawed before surgery, and if there is no need to use the graft, repeated freezing for its use is already excluded.

Closest to the claimed solution is a combined bone allograft and a method for its production (RU 2524618), which can be used in the treatment of patients with traumatic bone defects, with non-fused fractures, false joints, fractures with delayed consolidation. A combined allogeneic bone graft is a non-demineralized bone block obtained from the spongy bone of a donor and containing human type 1 collagen in the form of a sponge with a fine mesh structure obtained by freeze-drying a bone block impregnated with a collagen solution throughout the volume of the bone block. A method for producing a transplant includes manufacturing a non-demineralized bone block from the spongy bone of a donor, impregnating the bone block with a human type 1 collagen solution, followed by lyophilization under conditions ensuring the conversion of the collagen solution into a sponge with a fine mesh structure over the entire volume of the bone block. The biocompatible combined bone graft has mechanical strength, osteoconductive effect and stimulates osteogenesis. Lyophilization is the sequential passage of the following steps: freezing samples to a temperature of -40 ° C, creating a vacuum, maintaining this temperature for 1 hour, raising the temperature to + 36 ° C and holding the samples for 2 hours at this temperature. The bone block is impregnated with a collagen solution by drilling through holes with a diameter of 2 mm in various directions of the bone block, followed by immersing it in a 10% human type 1 collagen solution and pumping the collagen solution through the indicated holes with a syringe (without using a needle).

However, this graft is not convenient for strengthening the fracture area during fractures of the proximal humerus, because in this zone, the spongy bone passes into a tubular one and for reinforcing this area, a material sufficiently strong in fracture and having a cylindrical shape is needed. The graft is convenient for filling defects in the cancellous bone and stimulating osteogenesis in case of violation of fracture consolidation, but is not suitable for strengthening the fracture in the diaphyseal and metaphyseal areas of the bone. In addition, the method of saturating the transplant with a collagen solution does not ensure its maximum collagen saturation - filling natural and formed cavities, as well as the uniform distribution of collagen throughout the volume of the transplant, which significantly improves the conditions for fixation and subsequent differentiation of mesenchymal cells.

Thus, the technical problem is to obtain such a material (graft) that would strengthen the bone tissue of the humerus and reliably fix the fracture area, on the one hand, have an osteoconductive effect, on the other hand, and do not require special storage and pre-treatment conditions before use .

Disclosure of invention

The technical result of the invention is the creation of a bone allogeneic transplant, which strengthens the proximal humerus in the surgical treatment of complex multi-fragmented fractures of the shoulder, accompanied by bone deficiency and the creation of conditions to facilitate the reposition of fragments and joint fracture. The inventive transplant also has osteoconductive properties, can serve as a carrier of biologically active substances and does not require special storage conditions.

Strengthening of the bone tissue of the humerus and reliable fixation of the fracture area are realized due to the presence of the head, which does not allow the graft to fall into the bone marrow channel of the humerus, holding it until the fracture is fixed, fills the defect of the spongy bone of the shoulder head, due to the presence of the neck and upper part of the diaphysis fibula that reinforce the fracture area. The osteoconductive effect is realized by reducing the mass of the cortical and spongy non-demineralized bones by drilling holes with a diameter of 2 mm at a distance of 3-4 mm from each other and due to the presence of sponges from type 1 allogeneic collagen in the natural and formed by drilling. The sponge is hygroscopic, i.e. when the sponge is saturated with biologically active substances, the transplant can acquire osteoinductive properties.

The claimed technical result is provided by a combined allogeneic bone graft for the treatment of complex fractures of the proximal humerus, containing a non-demineralized bone block obtained from the donor bone, which is a fragment of the fibula 6-8 cm long, including the head, neck and part of the diaphysis, provided throughout surfaces through channels made with a diameter of not more than 2 mm, located at a distance of 3-5 mm from each other, while the natural cavities and formed openings of the bone block are filled with collagen type 1 of a person in the form of a sponge with a fine-meshed structure that can be formed by lyophilization of the bone block impregnated with a collagen solution.

The claimed technical result is also provided by a method for producing a combined allogeneic bone graft for the treatment of complex fractures of the proximal humerus, including the formation of a donor bone from a tibia frozen at a temperature of -40 ° C, a fragment comprising a head with a neck and part of the diaphysis with a total length of 6-8 cm; during the formation of the fragment, the periosteum, cartilage and soft tissue residues are removed, after which through holes of a diameter of not more than 2 mm are formed on the entire surface of the fragment at a distance of 3-5 mm from each other, followed by dehydration, degreasing and drying, after which the obtained perforated bone block they are impregnated with a collagen solution 1 (aqueous) of a human type, followed by lyophilization under conditions ensuring the conversion of the collagen solution into a sponge with a fine-mesh structure over the entire volume of the bone block, after which the resulting transplant is dehydrated, degreased and dried.

The bone block is impregnated with collagen solution by centrifugation, while the bone block is placed in a container with rigid walls, filled with a 0.75-0.8% human type 1 collagen solution so that it completely covers the bone, the container is closed with a lid and placed in a centrifuge, centrifugation is carried out with an acceleration of 100g for 30 min, after which the centrifugation session is repeated with the addition of collagen solution in the container to the initial level, the number of sessions is performed until the bone block is completely saturated with collagen, in which the collagen volume does not stop decreasing after the centrifugation session.

The perforated bone block is degreased, for which it is poured with a mixture of 95% alcohol and ether in a ratio of 1: 1 per day, then poured with pure ether for a day.

The resulting graft is dried in a fume hood for 24 hours at room temperature (18-24 ° C).

Brief Description of the Drawings

The invention is illustrated by drawings, where in FIG. 1 shows a general view of the graft; FIG. 2 - shows a diagram of the installation of the transplant into the bone marrow canal with suturing the tendons of the rotating cuff of the shoulder; in FIG. 3 shows a fracture of the proximal humerus fixed by a plate after reposition of fragments and tendons attached to the plate. In FIG. 4-7 presents the results of a study of a particular patient according to example 1 with a multi-fragmented fracture of the proximal humerus with bone deficiency; in particular in FIG. 4 is a radiograph of the left shoulder joint (direct posterior projection), FIG. 5 - MSCT of the left shoulder joint, A - horizontal plane, B - frontal plane, C - sagittal plane; in FIG. 6 - radiograph of the left shoulder joint 8 months after surgery. The fracture is fused. There are no signs of collapse of the humeral head. The diaphyseal perforated part of the graft is still visible; in FIG. 7 - MSCT of the left shoulder joint. The transplant is being rebuilt - there is no border between the cancellous spongy bone and the spongy bone of the transplant, which indicates a pronounced osteoconductive effect of the transplant, A - horizontal plane, B - frontal plane, B - sagittal plane; in FIG. 8-11 show the results of a study of a particular patient according to example 2 with a multi-fragmented fracture of the proximal humerus with bone deficiency, in particular, in FIG. 8 is a radiograph of the left shoulder joint (direct posterior projection); in FIG. 9 - MSCT of the left shoulder joint, A - horizontal plane, B - frontal plane, C - sagittal plane; in FIG. 10 - radiograph of the left shoulder joint 6 months after surgery. The fracture is fused. Small collapse of the humeral head. The diaphyseal perforated portion of the graft is still visible, in FIG. 11 - MSCT of the left shoulder joint. The graft is being rebuilt - the border between the cancellous spongy bone and the spongy bone of the transplant disappears, which indicates a pronounced osteoconductive effect of the graft.

The implementation of the invention

Below is a more detailed description of the proposed solution.

For the manufacture of a transplant, use the head, neck and part of the fibular diaphysis obtained during the posthumous donation in accordance with the law of the Russian Federation of December 22, 1992 No. 4180-1 “On transplantation of organs and (or) human tissues”. The fibula is obtained from the shin of a cadaver no later than 24 hours after death. A longitudinal outer incision along the lower leg exposes the entire fibula, remove it. The extracted material is frozen at a temperature of -40 ° C and quarantined until analysis for transmissible infections.

After confirming the absence of infections, a fragment is cut off from the frozen fibula, including the head of the fibula with the neck and part of the diaphysis in such a way that the total length is 6-8 cm. The periosteum, cartilage and soft tissue residues are removed with an electric band saw. Then through a drill with a diameter of 2 mm, through holes are formed over the entire surface of the bone at a distance of 3-5 mm from each other, thereby reducing the mass of the bone and creating niches for filling with a type 1 collagen solution. The resulting bone block is immersed in a 3% hydrogen peroxide solution and under vacuum suction minus 2 atmospheres to remove fat and bone marrow residues. The hydrogen peroxide solution is changed every 20 minutes until the solution becomes light. The next step, the bone is washed 3-4 times in physiological saline and again immersed in a 3% hydrogen peroxide solution and left in a refrigerator at + 4 ° C on a medical shaker. After 12-20 hours, bone fragments are immersed for dehydration in 95% alcohol and left for a day at a temperature of + 4 ° on a medical shaker. After extraction from alcohol, for degreasing, the bone is poured with a mixture of 95% alcohol and ether in a ratio of 1: 1 per day. Then fill in with pure ether for a day. The last step is passively drying the product in a fume hood for 24 hours. The bone block is ready for saturation with a type 1 collagen solution.

To increase the osteoconductive potential and increase the hygroscopicity of the graft, the bone is saturated with an aqueous collagen solution (for example, with a concentration of 0.75-0.8% by volume) in a special centrifuge. The graft is placed in a sterile disposable container with rigid walls and a lid (for example, a plastic tube with a screw cap). The container is poured with a human type 1 collagen solution so that it completely covers the bone, the container is closed with a lid and placed in a centrifuge. Centrifugation is carried out with an acceleration of 100g for 30 minutes The amount of collagen in the test tube decreases during centrifugation (goes to the bone), so the collagen is periodically added so that it again covers the graft and the centrifugation session is repeated until the collagen volume ceases to decrease. This is regarded as complete saturation of the bone with collagen.

After saturation of the product with collagen, it is frozen at a temperature of -80 °, placed in a lyophilic chamber and lyophilized for 2.5-4 hours until the collagen completely dries. After lyophilization, the collagen solution, which is located in the bone graft in the formed channels, is transformed into a hygroscopic sponge with a pronounced osteoconductive effect and, due to its hygroscopicity, can be a carrier of biologically active substances.

This transplant was used in the surgical treatment of complex multi-fragmented fractures of the proximal humerus, accompanied by bone deficiency.

If the patient has a three-four-fragment fracture of the proximal humerus against osteoporosis accompanied by bone deficiency, which is diagnosed with computed tomography of the shoulder joint, the proximal humerus is exposed with standard delto-pectoral access. After identification of the damaged structures - the head of the shoulder, large and small tubercles, the tendons of the subscapular, supraspinatus, infraspinatus and small round muscles are sequentially stitched with non-absorbable sutures (for example, Terylene 5, FiberWire 2). Using the threads as reins, the tendons and the remnants of the tubercles attached to them are bred to the sides. The bone marrow canal of the humerus and the subchondral bone of the humeral head are opened for review. The bone-cartilaginous part of the head in such a situation resembles an egg shell. The rehydration transplant obtained in a bone jar is soaked for 15 minutes in physiological saline or saturated with biologically active substances, for example, an autologous platelet lysate, platelet-rich plasma, and bone morphogenetic protein. After that, the transplant is inserted into the bone marrow canal by the diaphyseal part, where it falls to the head. One of the surfaces of the head of the fibula is beveled. This surface is oriented to the articular cavity of the scapula, because the angle between the diaphysis of the humerus and the head of the humerus after reposition should be approximately 130 °. By pulling the strings, the remains of the tubercles and the head of the shoulder are pulled onto the head of the fibula “like a hood on the head”. The beveled surface of the head of the fibula allows you to orient the head of the humerus at an angle of about 130 ° without effort. Using filaments, large and small tubercles are compared. A fluoroscope controls the position of the fragments. With a satisfactory position of the fragments, the threads are passed through special holes of the plate with angular stability for the proximal shoulder (DC or PHILOS). Tighten the threads, thereby correctly positioning the plate - 5-10 mm distal to the apex of a large tubercle and posterior to the crest of a large tubercle. Temporarily fix the plate to the head with a central spoke. The presence of a graft allows you to do this, because a transplant head consisting of cancellous bone replaces a bone defect in the head of the humerus. Then, 2-3 proximal screws locked in the plate are inserted through the plate into the head, which, thanks to the transplant, are firmly fixed in the spongy bone of the graft and the remains of the subchondral bone of the humeral head. The next step is the plate is attached to the diaphysis of the humerus with a cortical screw into the oval hole. The plate on the diaphysis should be located posteriorly and parallel to the crest of a large tubercle. After this, tubercles are fixed by tightening and tying the threads on the plate.

Clinical example 1. Patient M., 56 years old, turned to the SRI SP after falling on the street. Upon admission, a closed multi-fragmented fracture of the proximal metaepiphysis of the left humerus was diagnosed with displacement (see Fig. 4). On the 7th day, osteosynthesis of the proximal metaepiphysis of the left humerus was performed with a plate with angular stability with bone grafting by the claimed combined allogeneic transplant from the fibula head. In the postoperative period, the arm was alternately immobilized with a kerchief bandage for 6 weeks, the patient was engaged in therapeutic exercises. When control x-ray and MSCT 8 months after surgery revealed that there is no secondary displacement of fragments, the fracture is fused, the graft is rebuilt (see Fig. 6, 7).

Clinical example 2. Patient M., 76 years old, came to the SRI SP after falling on the street. Upon admission, a closed multi-fragmented fracture of the proximal metaepiphysis of the left humerus was diagnosed with displacement (see Fig. 8). On the 4th day, osteosynthesis of the proximal metaepiphysis of the left humerus was performed with a plate with angular stability with bone grafting by the claimed combined allogeneic transplant from the fibula head. In the postoperative period, the arm was alternately immobilized with a kerchief bandage for 6 weeks, the patient was engaged in therapeutic exercises. During control radiography and MSCT, 6 months after the operation, it was revealed that there was no secondary displacement of the fragments, the fracture was growing together, and the graft was rebuilding.

Claims (6)

1. Combined allogeneic bone graft for the treatment of complex fractures of the proximal humerus, containing a non-demineralized bone block obtained from the donor bone, which is a fragment of the fibula 6-8 cm long, including the head, neck and part of the diaphysis, equipped with through channels made with a diameter of not more than 2 mm, located at a distance of 3-5 mm from each other, while the holes of the bone block are filled with collagen type 1 person in the form of a sponge with a fine-meshed structure. 2. The transplant according to claim 1, characterized in that collagen type 1 of the person in the form of a sponge with a fine-mesh structure in the natural cavities and openings of the bone block is formed by freeze-drying the bone block soaked in a collagen solution. 3. A method for producing a combined allogeneic bone graft according to claim 1 for the treatment of complex fractures of the proximal humerus, including the formation of a donor bone from a tibia frozen at a temperature of -40 ° C, a fragment comprising a head with a neck and part of the diaphysis with a total length of 6-8 cm , during the formation of the fragment, the periosteum, cartilage and soft tissue residues are removed, after which through holes of a diameter of not more than 2 mm at a distance of 3-5 mm from each other are formed over the entire surface of the fragment, followed by its dehydration, degreasing and drying, after which the obtained perforated bone the block is impregnated with a human type 1 collagen solution, followed by lyophilization under conditions ensuring the conversion of the collagen solution into a sponge with a fine-mesh structure throughout the entire volume of the bone block. 4. The method according to p. 3, characterized in that the bone block is impregnated with collagen by centrifugation, while the bone block is placed in a container with rigid walls, pour 0.75-0.8 vol.% Type 1 collagen solution of a person, so that it completely covers the bone, the container is closed with a lid and placed in a centrifuge, centrifugation is carried out with an acceleration of 100g for 30 min, after which the centrifugation session is repeated with the addition of the collagen solution in the container to the initial level, the number of sessions is performed until the bone block is completely saturated with collagen, characterized by the conservation of collagen volume in the container after the next centrifugation. 5. The method according to p. 3, characterized in that for degreasing the perforated bone fragment is poured with a mixture of 95% alcohol and ether in a ratio of 1: 1 per day, then poured with pure ether for a day. 6. The method according to p. 3, characterized in that the drying of the perforated bone fragment is carried out in a fume hood for 24 hours.

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