RU2846165C1 - Method for minimally invasive treatment of bone cysts - Google Patents

Abstract

FIELD: medical science.

SUBSTANCE: invention refers to medicine, namely to traumatology and orthopaedics, and can be used in treating bone cysts. Clots of platelet-rich fibrin (PRF) are prepared by blood sampling from a patient’s vein. It is centrifuged for 15 minutes at speed of 1500 rpm. Cyst cavity is washed. Fibrinolysis inhibitor is introduced into the cyst cavity and the prepared PRF clots are introduced through a bone trocar of diameter of 10 mm.

EFFECT: method provides higher effectiveness of bone cyst ossification ensured by minimally invasive treatment.

1 cl, 2 tbl

Description

Field of technology to which the invention relates:

The invention relates to traumatology and orthopedics and can be used in the treatment of bone cysts.

Bone cysts are among the most common tumor-like diseases of the bones in childhood. They are most common in the first and second decades of a child's life, and, according to many authors, the destructive process is more aggressive when they occur early. Any bone in the body can be affected, but the most typical localizations are the long bones, vertebrae, heel bone, and pelvic bones.

There are three independent forms of bone cysts: solitary (SCC), aneurysmal (ACC) and a solid variant of aneurysmal bone cyst. Each type of bone cyst has distinctive radiological, pathomorphological properties and features of the clinical picture. A common feature of all bone cysts is the presence of a focus of bone tissue destruction. As the pathological focus increases, the cortical layer becomes thinner and the risk of a pathological fracture of the affected bone increases.

During the pathological process of bone cysts, three phases are distinguished:

1. Osteolysis phase - the cyst is active, located in close proximity to the growth zone, characterized by high osteolytic activity of the contents of the pathological cavity and high intraosseous pressure (IOP) values.

2. The delimitation phase - the activity of the cyst decreases, it is gradually separated from the growth zone by a layer of healthy bone tissue, characterized by some decrease in osteolytic processes and intracranial pressure, and the appearance of a rim of osteosclerosis along the boundaries of the pathological cavity.

3. The reparation phase - the cyst is inactive, it is usually located in the diaphysis, and is characterized by a significant decrease in the osteolytic activity of the contents of the cyst cavity and the indicators of intracranial pressure, as well as the predominance of bone tissue reparation processes and a gradual decrease in the lesion until it is completely replaced by bone tissue (bone tissue reparation).

Solitary bone cysts, when examined by X-ray, are a homogeneous focus of bone tissue destruction. The cortical layer of such a cyst may be fusiformly swollen, thinned, but continuous (the exception is the presence of a pathological fracture). There is no reaction of the periosteum and surrounding tissues. Clinical manifestations of this type of cyst are usually not expressed. In 75% of cases, the first symptoms are detected when a pathological fracture of the affected bone occurs or are an accidental X-ray finding during an X-ray examination for other indications. When such cysts occur, unexpressed pain of an indefinite nature or an accidentally discovered thickening of the affected bone is possible. Morphological examination using a microscope shows that the wall of the cavity of a solitary bone cyst is represented by a thin plate of bone of any type of structure (cortical, spongy, compact, lamellar, etc.). From the inside, the cavity is lined with a thin layer of loose fibrous connective tissue. Multinucleated giant cell osteoclasts may be present in this tissue, and deposits of osteoid masses are also found.

Aneurysmal bone cysts are a focus of bone tissue deconstruction of a cellular structure with a spindle-shaped swelling of the affected bone, thinning and possible partial disruption of the cortical layer. Clinically, complaints of pain in the affected segment, dysfunction of nearby joints, local increase in the vascular pattern of the skin and local hyperthermia are characteristic.

A solid variant of an aneurysmal bone cyst (giant cell reparative granuloma) is a cavity filled with a tissue component and is characterized by an aggressive destructive process in the bone. Due to the multitude of small cavities, the aneurysmal bone cyst has a cellular appearance, reminiscent of a honeycomb. In these cavities, a small amount of dark cherry fluid or elastic, smooth, shiny cherry-colored blood clots can be found. The partitions of the cavities are soft-elastic or with bone inclusions. Microscopic examination reveals clusters of erythrocytes in the cavities. The walls of the cell-cavities consist of fibrous connective tissue of varying thickness: from thin layers to extensive fields. In the connective tissue, there are vascular-like cavities of various diameters, in the walls of which a lining of endotheliocyte-like cells can be found. An obligatory component of aneurysmal cysts are multinucleated giant cells (single or multiple clusters), which can imitate a giant cell tumor. Osteoid is present in the cyst walls, and newly formed bone beams may be encountered. Sometimes, islets of hyaline cartilage tissue can be found in the walls of an aneurysmal cyst. In addition, an inflammatory reaction may be present.

State of the art:

There are currently two main treatments for bone cysts:

- a puncture method based on the introduction into the cavity of substances that help reduce lytic processes in the lesion, reduce intracranial pressure and stimulate bone tissue regeneration;

- and surgical treatment, including marginal resection of the affected bone, removal of the cyst membranes and alloplasty using various types of bone-substituting implants.

A method for surgical treatment of bone cysts is known from the state of the art, including marginal resection, removal of pathological tissue, alloplasty of the cavity with allografts of biological (animal and human) origin. When the ICP in the cavity of an aneurysmal bone cyst increased by more than 350 mm H2O, the cyst was assessed as active, and a series of drug-diagnostic punctures were additionally performed with the introduction of protease inhibitors (aprotinin) into the cyst cavity. The purpose of the operation was to reduce the ICP by at least 2 times. In 20 cases, selective embolization of the feeding vessels was additionally used before surgical treatment in the specified volume to reduce intraosseous pressure. Removal of pathological tissue and treatment of the cyst cavity when it was located in close proximity to the growth zone were performed under intraoperative X-ray control to exclude damage to the growth plate. For the treatment of 8 patients with inactive aneurysmal bone cysts, a wait-and-see approach was not used: immediately after diagnosis, marginal resection was performed with alloplasty using cortical or cancellous grafts depending on the location and extent of the lesion.

The technique has many disadvantages, the main one being the high relapse rate: relapse of the disease in this group of patients occurred in 7 patients (19%). In addition, it is worth noting that almost all patients with active ACC required repeated surgical interventions. Of the 8 patients with inactive ACC, in 1 case there was a residual cavity measuring up to ¼ of the bone diameter, which did not require repeated surgery. The long recovery period is also noteworthy - from 9 to 22 months (14 months on average).

Also known from the state of the art is a method of surgical treatment of bone cysts using plastic surgery in the form of a "bundle of firewood", described in patent RU 2386408 C2, 20.04.2010. However, its high traumatic nature is widely criticized by specialists.

The literature also describes a method for surgical correction of bone cysts by performing bone osteotomy in the area between healthy and altered bone tissue, intraosseous resection of the pathological focus, followed by the introduction of a healthy bone fragment into the bone cavity. The second stage involves the formation of a distraction regenerate and compression-distraction osteosynthesis according to Ilizarov (ANDREEV P.S. Surgical treatment of bone cysts and tumor-like formations of long tubular bones of metadiaphyseal localization // PM. 2015. No. 4-1 (89). URL: https://cyberleninka.ru/article/n/hirurgicheskoe-lechenie-kostnyh-kist-i-opuholevidnyh-obrazovaniy-dlinnyh-trubchatyh-kostey-metadiafizarnoy-lokalizatsii).

The described method has the following disadvantages: when performing this method, difficulties arise when introducing a healthy bone fragment into the bone cavity due to the narrowing of the medullary canal. In addition, when forming a regenerate, the bone cavity is not completely filled with distraction bone regenerate, which is explained by the presence of the periosteum and cortical layer on the healthy bone fragment introduced into the bone cavity, as a result of which bone cavities remain after the described method. An obvious disadvantage of the method is the impossibility of short-term compensation for shortening of the limb length, as well as everyday and social inconveniences associated with long-term wearing of the Ilizarov apparatus.

Also, the state of the art provides the results of the analysis of the efficiency of various surgical methods of filling the bone cyst cavity: the use of cancellous crumbs, replacement of the defect with decalcified allografts, etc. (PAVLENKO N.N. et al. Some aspects of diagnostics and surgical treatment of bone cysts // Bulletin of Russian universities. Mathematics. 2015. No. 2. URL: https://cyberleninka.ru/article/n/nekotorye-aspekty-diagnostiki-i-hirurgicheskogo-lecheniya-kostnoy-kisty). The study included patients who underwent the following surgical interventions: marginal resection - 122 patients: marginal resection, removal of the pathological focus, replacement of the defect with cortical allografts - 30 patients and 3 - metal osteosynthesis with screws; Marginal resection, removal of pathological focus, defect replacement with autografts - 35 patients and 2 patients - osteosynthesis using the Ilizarov apparatus; Marginal resection, removal of pathological focus, defect replacement with cancellous crumbs - 30 patients and 8 patients - with autobone in combination; Marginal resection, removal of pathological focus, defect replacement with decalcified allografts - 5 patients; Marginal resection, removal of pathological focus, without defect replacement - 9 patients. Segmental resection of bone cyst was performed in 8 patients: segmental resection, removal of pathological focus, defect replacement with cortical allografts, osteosynthesis using the Ilizarov apparatus - 3 patients; segmental resection, removal of pathological focus, defect replacement with autografts, metal osteosynthesis with screws and a plate - 5 patients; 9 - replacements were not performed due to the presence of a lesion less than 1.5 cm in size, which does not affect the mechanical strength of the bone and does not cause any clinical manifestations. The defect cavity after removal of the pathological lesion was treated with the following: laser irradiation - 12 patients; carbolic acid (three times) - 109 patients; cryotherapy - 5 patients; 24 - not performed. To replace defects in 16 patients (11.1%), the domestic biocomposite bone plastic material "Kollapan" (registration certificate of the Ministry of Health No. 7289488) was used, in 4 patients - the drug LitAr (registration certificate of the Ministry of Health No. 29 / 13050501 / 3011-02).

According to the results of the analysis, complete reorganization of the anatomical structure of bone tissue was observed only in 79.9% of cases; residual cavities were observed in 15.9%; relapse was noted in 4.2% of cases.

Surgical treatment is also widely described in foreign literature. Studies with a long-term follow-up period are presented, which show a significant increase in the recurrence rate over time: 17% after the first year after surgery, 23% after the second, 34% after five years according to one author, and 7% after the first year, 20% after the second, 40% after five years and 43% after 10 years after surgery (KEVIN DÖRING et al. Results in the surgical treatment of aneurysmal bone cysts - A retrospective data analysis, Orthopaedics & Traumatology: Surgery & Research, Volume 108, Issue 4, 2022, 103095, ISSN 1877-0568, https://doi.org/10.1016/j.otsr.2021.103095, DÖRING K. et al. Open surgical treatment of unicameral bone cysts: A retrospective data analysis. Wien Klin Wochenschr. 2024 Oct; 136 (19-20): 547-555. doi:10.1007/s00508-023-02267-4. Epub 2023 Aug 31. PMID: 37650964; PMCID: PMC11464551).

One of the serious disadvantages of the surgical method of treatment is that some materials used for bone grafting, such as Osteomatrix (bone allocollagen, bone allosulfated glycosaminoglycans, xenohydroxyapatites), used in patent RU 2562514 C1, can cause febrile fever in children, which limits its use for this age group (DROZDETSKY A.P. et al. Personal experience of using bone grafting materials in the surgical treatment of bone cysts in children, https://cyberleninka.ru/article/n/sobstvennyy-opyt-primeneniya-kostnoplasticheskih-materialov-pri-hirurgicheskom-lechenii-kostnyh-kist-u-detey).

Puncture methods of treating bone cysts with the introduction of steroids or other substances (autogenous bone marrow, demineralized bone matrix, hydroxyapatite, calcium sulfate, calcium phosphate, etc.) are minimally invasive treatment methods. The therapy is based on the prostaglandin effect and a decrease in pressure in the cyst. The number of punctures varies from 2 to 5. According to literary data, the minimum number for closing a bone cyst is 3 punctures with an injection of the drug. Puncture-injection methods are easy to perform, while damage to the growth zone is excluded, a minimal cosmetic defect, the patient is in hospital for a short period and after discharge can return to a normal lifestyle without stress. Despite the fact that various methods for reducing the duration of treatment are used, for example in patent RU 2160061 C2, as well as various methods for reducing the trauma of treatment, for example in patent SU 1025419 A1, the effectiveness of this method as a whole is in the range of 40 to 80%. For example, a study is described that indicates that the frequency of cyst healing is 67% (MEIRLAEN S. et al. Treatment of bone cysts by percutaneous injection of demineralized bone matrix mixed with bone marrow. Acta Orthop Belg. 2022 Sep; 88 (3): 559-567. doi: 10.52628/88.3.10051. PMID: 36791710). This may be due to the fact that the effectiveness of the method depends to a greater extent on the type of drug administered, and modifications to the administration technique are not so significant. In addition, the negative aspects of the puncture-injection method include the negative impact, especially on a growing organism, of the administered steroids (systemic response to steroids - Cushing's syndrome).

Minimally invasive methods of treating bone cysts also include the flow drainage method, which consists of establishing a system of constant drip irrigation of the cavity with solutions with the introduction of drugs in order to reduce hydrostatic pressure in the cyst, remove decay products that support the pathological process described in patents RU 2420243 C1 and RU 2069995 C1. The total drainage time is 9-10 days, followed by filling the cyst cavity with allogeneic demineralized bone matrix crumbs. A positive result was noted in 91.75% of cases. The disadvantage of this method is the duration of the procedure and discomfort for the child, as well as repeated general anesthesia.

A method of introducing a solution of pre-fractionated and lyophilized blood plasma into the cavity of a newly formed bone is known, described in patent RU 2193868 C2. The plasma is fractionated to obtain components that are salted out at an ammonium sulfate concentration of more than 30% and not less than 50% of saturation. The relative molecular weight is 20-30 kD. The method allows reducing the antigen load on the body and preventing postoperative complications. A disadvantage of the described technique may be the presence of neutrophils and their contents, which may cause inflammation and may affect the destruction of bone tissue, thereby increasing the risk of pathological fractures.

Taking into account the above, there is a need to search for new methods of treatment, with the help of which it would be possible to achieve more accelerated treatment in combination with less trauma, lower frequency of relapses and frequency of pathological fractures in the remote observation period. We propose to solve these problems by using the puncture method, which allows achieving low invasiveness, using the biopreparation of fibrin enriched with platelets - PRF (Platelet-Rich Fibrin).

PRF is already used in dental practice as a method of biostimulation of soft and hard tissue healing and regeneration in dental practice while preserving the alveolar ridge. PRF contains platelet-derived growth factors, hormones and bioactive components such as cytokines, which have demonstrated the ability to stimulate angiogenesis and tissue regeneration at all stages of wound healing. In addition, the concentration of leukocytes present in the PRF matrix plays a vital role in tissue healing and regeneration as part of the osteoimmune response. The benefits of incorporating autologous platelet-Rich Fibrin concentrates in alveolar ridge preservation have been reported to include: decreased healing time, improved angiogenesis and bone regeneration, and socket sealing due to the fibrin-formed matrix (UCER C. et al. Alveolar Ridge Preservation with Autologous Platelet-Rich Fibrin (PRF): Case Reports and the Rationale. Dent. J. 2023, 11, 244. https://doi.org/10.3390/dj11100244; SALGADO-PERALVO Á.-O. et al. Understanding Solid-Based. Platelet-Rich Fibrin Matrices in Oral and Maxillofacial Surgery: An Integrative Review of the Critical Protocol Factors and Their Influence on the Final Product. Medicina 2023, 59, 1903. https://doi.org/10.3390/medicina59111903).

There is a technique for introducing PRF into the cyst cavity along with a liquid form of demineralized bone matrix and bone marrow aspirate concentrate. In a published study by Luca Cevolani et al. (2021), ossification of the cyst cavity after the proposed procedure was 100% regardless of the number of procedures, however, when assessing the ossification of the cyst cavity, the authors considered the result satisfactory with ossification of more than 51% of the cyst cavity, which may not be complete ossification in every case. The authors also did not evaluate the thickness of the cyst wall, although this is the main risk factor for the formation of a pathological fracture. In addition, patients undergoing this procedure require bone marrow sampling from the posterior superior iliac bone, which lengthens and complicates the procedure, and can also potentially lead to complications. Allogeneic bone material is used to fill the cyst cavity, which in some cases can lead to an unpredictable reaction in the cyst focus. In addition, against the background of high cyst activity, a tendency for allogeneic transplants to be resorbed is known.

We believe that the closest method to the proposed one is one that includes the creation of osteoperforation holes with the passage of both cortical layers with a drill directed at an angle to the bone axis, the installation of intraosseous needles in the formed channels, followed by washing of the pathological focus (see Russian patent No. 2420243, 2011) and the introduction of demineralized bone matrix into the focus.

However, such a technique may result in leakage of drugs into soft tissues and cessation of perfusion of the cyst cavity. Demineralized bone matrix is often subject to lysis under conditions of high bone cyst activity.

Disclosure of the essence of the invention:

The objective of the proposed invention is to reduce the invasiveness of surgical intervention in the treatment of bone cysts by eliminating open intervention methods, and to increase the efficiency of ossification of the cyst cavity by reducing the total number of procedures required for ossification of the cyst cavity.

The technical result of the proposed method consists in increasing the efficiency of ossification of bone cysts. The said technical result is achieved along with a reduction in the number of surgical interventions, as well as in the absence of the need to perform open bone grafting.

The specified technical result is ensured by a method of minimally invasive treatment of bone cysts, including obtaining platelet-rich fibrin (PRF) clots by taking blood from a patient's vein, centrifuging the blood for 15 minutes at a speed of 1500 revolutions per minute: washing the cyst cavity, introducing a fibrinolysis inhibitor into the cavity, followed by introducing the obtained PRF clots through a bone trocar with a diameter of 10 mm.

When washing the cyst cavity through a bone trocar with subsequent introduction of PRF through it, a drainage hole up to 1 cm thick remains in the bone. The presence of this hole allows to reduce the pressure in the cyst cavity. PRF clots immersed in the cyst cavity are a matrix for anchoring stem cells, sources of growth factors and chemoattractants, as well as anti-inflammatory cytokines, which together allow to locally enhance osteogenesis, slow down the inflammatory process, and lead to the closure of the cyst cavity in the area into which the substance is introduced.

Implementation of the invention:

Before the intervention, 72 ml of blood is taken from the patient's vein to obtain PRF clots. The blood is placed in 9 ml polypropylene tubes (8 tubes). The blood is centrifuged for 15 minutes at 1500 rpm using a cup-type centrifuge with a radius of 10 cm.

Under general anesthesia and periodic X-ray control of fluoroscopy, after careful treatment of the surgical field with antiseptic solutions and its draping, a puncture of the skin and soft tissues is made with a bone needle, bringing the end of the needle to the cyst wall. Under X-ray control, a puncture of the cyst wall is made, and the position of the needle tip in the cyst cavity is controlled. A puncture of the cyst is made in a similar manner at a distance of at least a centimeter from the puncture site of the previous needle. Contrasting of the cyst with a water-soluble contrast solution is carried out in order to clarify the anatomy of its cavities and connections between the latter. Through bone needles, the cyst cavity is washed successively with a 0.9% sodium chloride solution - 400 ml, then a solution of aminocaproic acid 200 ml is introduced. The bone needles are removed from the cyst cavity. A 1 cm skin incision is used to insert a 10 mm diameter bone biopsy trocar into the cyst cavity along a cone guide, for example, into the area with previously maximum filling with contrast agent. PRF clots are introduced into the cyst cavity through the bone trocar. A nodal suture is applied to the skin and an aseptic dressing is applied.

As noted earlier, anti-inflammatory cytokines released from PRF clots help reduce inflammation in the cyst cavity after its release (rinsing) from the contents. Platelet growth factors, gradually and slowly released from clots, provide osteogenic stimulation. The fibrin lattice in the PRF clots helps attract stem cells and anchor them to the matrix. Centrifugation of the patient's own blood for 15 minutes at 1500 rpm helps form clots of a size that is convenient to introduce through a 10 mm trocar. In addition, it is this speed that creates sufficient centrifugal force to separate the blood into layers (erythrocytes, PRF, platelet-poor plasma), but not so high as to damage platelets or fibrin. Higher speed may damage platelets or promote their mixing with red blood cells, reducing their concentration in the PRF clot, which obviously leads to a decrease in the efficiency of cyst ossification. Lower speed than suggested may result in insufficient cell separation, leaving platelets in the plasma, which will also reduce the efficiency of the injected clot. The selected centrifugation time promotes the formation of a dense fibrin network that retains platelets and growth factors. Shorter time does not allow fibrin to fully polymerize, making the clot friable, and longer time may cause excessive compaction of fibrin, hindering the release of growth factors or lead to cell lysis and degradation of growth factors.

In addition to the fact that the selected centrifugation parameters provide a high concentration of platelets in the clot and an optimal fibrin structure for the slow release of growth factors (VEGF, TGF-β, PDGF), it is precisely with the specified centrifugation parameters that the minimum number of leukocytes remains in the clot, which reduces inflammatory reactions, which also obviously leads to increased treatment effectiveness.

Washing the cyst cavity helps to free the cyst cavity from fibrinolytic enzymes, proinflammatory cytokines and metabolites that suppress the activity of osteoblasts, activate osteoclasts, increasing bone resorption.

Fibrinolysis inhibitors are also administered before PRF to increase the effectiveness of therapy. The fact is that cysts in most cases contain proteolytic enzymes (e.g., plasmin) that destroy fibrin, the basis of PRF, which reduces its action time and reduces the regenerative potential. In addition, preliminary administration of a fibrinolysis inhibitor helps to prolong the release of growth factors, which increases the duration of their action in the cyst cavity, improving ossification processes, both by increasing the duration of inflammation suppression and by increasing the duration of preservation of the framework for cell migration and angiogenesis. Thus, fibrinolysis inhibitors create an optimal environment for PRF operation, blocking the destruction of its fibrin framework and enhancing the regenerative potential.

Fenestration of the cavity during the insertion of a 10 mm bone trocar also plays an important role in increasing the efficiency. Decompression reduces vascular compression, restoring microcirculation in the bone. Reducing ischemia prevents apoptosis of osteogenic cells, and reducing pressure eliminates pathological loads on osteocytes, which respond to changes in stress, activating bone remodeling; secrete signaling molecules (for example, prostaglandins) stimulating osteogenesis. In addition, decompression triggers mechanotransduction - the process of converting mechanical signals into biochemical ones. Key pathways: Wnt/β-catenin - enhances osteoblast proliferation, BMP/Smad - regulates the differentiation of MSCs into osteogenic cells, RANKL/OPG - suppresses bone resorption, reducing osteoclast activity. The 10 mm hole size was chosen because it ensures optimal decompression without significant weakening of the bone, which minimizes the risk of fractures due to the preservation of structural integrity. Experimental studies on the size of the decompression hole in bone cysts confirm that the 10 mm size, compared with larger sizes, reduces the healing time from 12-18 months to 6-8 months, reduces the frequency of relapses by 2-3 times, and also accelerates the filling of the cavity with new bone tissue by 30-40% in comparison groups when introducing identical drugs into the bone cavity with smaller and larger sizes of the decompression hole.

To assess the effectiveness of the proposed method, the following study was conducted from 2021 to 2024:

Patients with bone cysts of identical or comparable size were divided into 6 groups. The first group (1) was treated according to the closest analog method, namely, osteoperforation holes were made by passing both cortical layers with a drill directed at an angle to the bone axis, intraosseous needles were installed in the formed channels, followed by washing of the pathological focus and introduction of demineralized bone matrix (DBM) into the focus. Patients of the second group (2) were given a decompression hole in the bone with a 12 mm trocar, the cyst was washed and drugs were introduced into the cyst cavity to reduce inflammation. Patients of the third group (3) were given a decompression hole with a 10 mm trocar, the cyst was washed and PRF clots were introduced, obtained by centrifuging the patient's blood for 15 minutes at a speed of 1500 rpm. In patients of the fourth group (4), a decompression hole was made with a trocar 8, the cyst was washed and PRF was introduced, obtained in the same way as in group 3.

The patients of the fifth group (5) had a decompression hole made with an 8 mm trocar, fibrinolysis inhibitors were administered, and PRF obtained by the method described above was administered. The patients of the sixth group (6) had a decompression hole made with a 10 mm trocar, fibrinolysis inhibitors were administered, and PRF obtained by the method described above was administered.

The treatment results for the patient groups are presented in Table 1.

Table 1. Comparative results of bone cyst treatment

Evaluation parameters 1 2 3 4 5 6 Osteogenesis rate, months Moderate.
(3-4 months) Low
(6-8 months) Average
(4-5 months) Average
(4-5 months) Tall
(3-4 months) Highest (2-3 months) Volume of bone regeneration 60-70% 30-40% 50-60% 50-60% 70-80% 95-98% Cyst recurrence rate 15-20% 40-50% 25-30% 25-30% 10-15% 2-4% Concentration of growth factors Low (DCM does not stimulate active release) Low Average (PRF) Average (PRF) High (PRF + fibrin stability) Highest (PRF + inhibitors) Reduced inflammation Moderate (perforation injures tissue) Average (rinsing + preparations) Average (PRF) Average (PRF) High (PRF + inhibitors) The highest Fibrin clot stability Low (no PRF) Low Medium (PRF without protection from fibrinolysis) Medium (PRF without protection) High (inhibitors + PRF) Highest (inhibitors + optimal hole size) Blood supply
in the defect zone Violated (perforation injury) Moderate Good (decompression 10 mm) Satisfactory (8 mm) Good Optimal (10 mm + inhibitors) Complications Risk of fractures;
Infection Relapses; slow healing Minimal Minimal Rare None

According to the obtained data, the treatment of patients in group 6 demonstrated the greatest efficiency, which is explained by the optimal size of the decompression hole, which ensures a balance between effective pressure reduction and preservation of bone strength, through which PRF clots of optimal size with optimal structure and platelet concentration are introduced, while the clots are introduced after evacuation (washing) of the cyst contents and the introduction of fibrinolysis inhibitors, which ensures maximum stability of the fibrin matrix and prolonged release of growth factors.

Group 1 (osteoperforation + DCM) is inferior due to mechanical damage to the bone, lack of biological stimulation (PRF); groups 3-4 (PRF without inhibitors) are less effective, since fibrinolysis in the cyst destroys PRF, group 5 is worse than group 6 due to insufficient decompression (smaller hole diameter).

In addition, a comparative analysis of PRF clots obtained by centrifugation at different centrifugation durations and speeds was carried out:

- 10 minutes 1000 rpm;

- 20 minutes 2000 rpm;

- 15 minutes 1800 rpm;

- 15 minutes 1500 rpm.

The results obtained are presented in Table 2.

Table 2. Comparative characteristics of PRF clots obtained with different centrifugation parameters

Parameters Group 1:
10 min, 1000 rpm Group 2:
20 min, 2000 rpm Group 3:
15 min, 1800 rpm Group 4:
15 min, 1500 rpm Platelet concentration 2-3×↑ from the initial level 1.5-2×↑ (partial lysis) 3-4×↑ 4-5×↑ (optimal division) Fibrin matrix density Loose, unstable (40% density) Hard, brittle (70% density) Moderately dense (80% density) Dense, elastic (95% density) Concentration of growth factors - VEGF (pg/ml) 120 ± 15 200 ± 20
(quick release) 250 ± 25 350 ± 30 (extended release) - PDGF (pg/ml) 80 ± 10 150 ± 15 180 ± 20 220 ± 25 - TGF-β (ng/ml) 8 ± 1 12 ± 2 15 ± 2 20 ± 3 Platelet viability 60% (low activation) 40% (damage at high speeds) 75% 95% (maximum safety) Resistance to fibrinolysis 1-2 days 3-4 days (hard matrix) 5-6 days 7-10 days (ideal structure) Leukocyte infiltration High (↑ inflammatory risk) Moderate Low Minimum

Thus, it is the clots obtained in accordance with the proposed method that have the highest concentration of platelets due to the balance between the speed and time of centrifugation, which prevents their damage; a dense fibrin network, which is formed due to optimal polymerization of fibrin, providing a slow release of growth factors; the maximum concentration of VEGF, PDGF, TGF-β. In clots obtained by centrifuging the patient's blood for 10 minutes at a speed of 1000 rpm, due to insufficient centrifugation force, the concentration of platelets in the clot is insufficient, in addition, the matrix is loose, the growth factors are "washed out" in 1-2 days. In clots obtained as a result of centrifuging blood for 20 minutes at a speed of 2000 rpm, high revolutions damage platelets and fibrin, reducing their viability; the matrix is rigid, but fragile, due to which it does not provide a prolonged effect. Centrifugation for 15 minutes at 1800 rpm results in partial lysis of platelets, which reduces the effectiveness of the clots.

Claims (1)

A method for minimally invasive treatment of bone cysts, including: obtaining platelet-rich fibrin (PRF) clots by taking blood from a patient's vein, centrifuging the blood for 15 minutes at 1500 rpm; washing the cyst cavity; introducing a fibrinolysis inhibitor into the cyst cavity, followed by introducing the obtained PRF clots through a 10 mm diameter bone trocar.