A method for preparing an osteotomy gap filling material for high tibial osteotomy

Abstract

The application discloses a preparation method of an osteotomy gap filling material for tibial high osteotomy. The method comprises the following steps: (1) adding 30-50 parts of biological bone cement powder, 30-50 parts of functional aggregate particles, 5-20 parts of starch powder and 0-2 parts of water-soluble phosphate into a container, and then oscillating and mixing uniformly after being closed; (2) adding 40-80 parts of polyethylene glycol into the container in step (1) after being melted, and then cooling to room temperature after heating and stirring to form a mixture; and rubbing for 1-2 min to form a dough, so that the osteotomy gap filling material for tibial high osteotomy is obtained. The material obtained by the method is anhydrous plastic solid before blood absorption and solidification, can be rubbed into a required shape at will, and can be fully filled into a bone defect to block the osteotomy surface and stop bleeding; the material composition has good osteogenesis promotion capacity and gradient degradation, and finally forms bone healing at the osteotomy gap.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical materials, and particularly to a preparation method of a bone gap filling material for tibial high osteotomy. BACKGROUND

[0002] Open wedge high tibial osteotomy (OWHTO) is an effective method for the treatment of knee osteoarthritis. The principle is to correct the lower extremity alignment by osteotomy and to transfer the pressure of the knee joint from the affected compartment to the normal compartment, thereby relieving pain and delaying the progression of arthritis. After the osteotomy and distraction of the tibia, a wedge-shaped bone defect gap is formed. It is reported that there is a 20%-30% incidence of hinge fracture and a bone nonunion rate as high as 4.6%. It is usually necessary to fill the osteotomy gap with autologous bone or artificial bone material to avoid loss of the orthopedic angle.

[0003] Because the osteotomy distraction distance depends on the correction angle of the patient's lower extremity alignment, the angle and height of the wedge-shaped bone defect at the osteotomy gap are different for different patients. The artificial bone graft materials commonly used in open wedge high tibial osteotomy at present mainly include pre-shaped wedge-shaped calcium phosphate ceramic blocks and calcium phosphate particles or paste for filling. The wedge-shaped calcium phosphate ceramic block has a certain structural support function, but it is difficult to adapt to the size and shape of the osteotomy gap of different patients and needs to be further machined during the operation. In addition, the block is difficult to fully adhere to the bone wound surface and cannot effectively stop bleeding on the bone wound surface. Granular, sheet-shaped or paste-shaped calcium phosphate can be easily filled into the osteotomy gap, but it cannot provide additional support strength. Calcium phosphate cement has the basic characteristics of self-curing, which can achieve shape adaptation during injection and strength support after hardening. However, it needs to be mixed with cement powder and curing liquid in advance and used within the working time window, and it is not ideal for the treatment of sudden bleeding. There is currently a lack of artificial bone materials for osteotomy gap that combine shape adaptation, mechanical support, wound hemostasis function, and are easy to use.

[0004] The osteotomy process, gap distraction and soft tissue release during surgery can cause a large amount of bleeding, which can lead to hematoma, delayed wound healing, superficial cellulitis, and affect bone healing in the gap. It is reported that the incidence of accidental hematoma is 1.5%-6% and the incidence of wound complications is 5%-7%. Clinically, tranexamic acid and gelatin sponge are commonly used to control bleeding. Due to the postoperative exposure of the osteotomy surface, even after sufficient soft tissue hemostasis and the use of hemostatic drugs, postoperative bleeding is still unavoidable. It is necessary to place a drainage tube to drain the blood and avoid blood accumulation in the subcutaneous or intermuscular space, which can cause pain, calf swelling and increased tension of the incision. However, the use of a drainage tube can also increase the amount of bleeding, increase the risk of infection, and affect the patient's early functional exercise. If a filling material is used to seal and hemostasis the osteotomy gap, it can effectively prevent postoperative bleeding of the osteotomy surface and reduce the use of drainage tubes and related complications.

[0005] In the current technology, the patent "a kind of self-curing high-strength macromolecular glue preparation method "(patent number ZL2015109767808) with calcium phosphate and starch as the main component of bone cement, with self-curing, degradable and high mechanical strength etc., suitable for the filling and repair of bone defect.But this product still needs to be mixed with cement powder and aqueous solution on site when used, which cannot match the hemostatic operation method of bone gap. SUMMARY

[0006] The technical problem to be solved by the present application is to provide a preparation method of a bone gap filling material for tibial high osteotomy in view of the deficiencies in the current technology.The method adopts a cement-aggregate-fiber composite structure similar to reinforced concrete, which is composed of bone cement as the cementitious matrix, and dispersed aggregate particles and starch to form a cement-aggregate-fiber three-component composite structure with good mechanical strength and anti-disintegration property;and polyethylene glycol is used as a water absorbing agent to absorb blood or tissue fluid in the body to induce the cement matrix to solidify.This pre-mixed self-curing design combines the shape adaptation of soft materials and the mechanical support of rigid materials.The material obtained by the present application is a non-aqueous plastic solid before solidification, which can be stored for a long time and can be kneaded into any desired shape and fully packed into bone defects to block the osteotomy surface.After in-situ water absorption and solidification, it can provide mechanical support in the bone gap.The material composition has good osteogenesis ability and gradient degradation, and finally forms bone healing in the bone gap.

[0007] The technical solution of the present application is:

[0008] A preparation method of a bone gap filling material for tibial high osteotomy, comprising the following steps:

[0009] (1) take 30-50 parts of biological bone cement powder, 30-50 parts of functional aggregate particles, 5-20 parts of starch powder and 0-2 parts of phosphate into a container, mix uniformly after sealing and oscillation;

[0010] The phosphate is sodium hydrogen phosphate or sodium dihydrogen phosphate.

[0011] The biological bone cement powder is one of calcium phosphate, calcium sulfate, calcium silicate and magnesium phosphate or a combination thereof.

[0012] Preferably, the bone cement powder is calcium phosphate bone cement powder.

[0013] The sources of the functional aggregate particles include, but are not limited to, bioceramic particles, autologous bone particles, allogeneic bone particles, or combinations thereof, wherein the sources of the bioceramic particles are calcium phosphate, dicalcium phosphate, calcium sulfate, magnesium phosphate, dicalcium phosphate dihydrate, bioactive glass, or combinations thereof.

[0014] The compressive strength of bioceramic particles is 2-100 MPa.

[0015] Preferably, the functional aggregate particles are calcium phosphate ceramic particles or allogeneic bone.

[0016] The starch mentioned includes raw starch and modified starch. The modification methods of starch include, but are not limited to, gelatinization, cross-linking, acidification, etherification, grafting, or combinations thereof.

[0017] Preferably, the starch powder is cross-linked Waxy starch.

[0018] (2) At a temperature of 60-100℃, 40-80 parts of polyethylene glycol are melted and added to the container in step (1). After heating for 0.5-2 hours, the mixture is stirred with a glass rod for 0.5-2 minutes to form a uniform mixture and then cooled to room temperature. The mixture is kneaded for 1-2 minutes to form a dough-like consistency, which yields the osteotomy gap filling material of the present invention for high tibial osteotomy.

[0019] The polyethylene glycol includes a mixture of one or more polyethylene glycols with a relative molecular mass between 200 and 6000.

[0020] Preferably, polyethylene glycol 1500 and polyethylene glycol 400 are mixed and melted in a mass ratio of 4:1.

[0021] The application of the osteotomy gap filling material prepared by the method for high tibial osteotomy includes the following steps:

[0022] (1) After tibial osteotomy using an oscillating saw during the operation, the osteotomy area is slowly opened until the required opening angle is obtained.

[0023] (2) After kneading the filling material into a suitable shape, stuff it into the osteotomy gap, press and adjust the shape of the material to ensure that it fully fills the bone defect and seals the bleeding.

[0024] (3) Use an internal fixation system to maintain the osteotomy height.

[0025] Step (3) can be completed before or after step (2) depending on the surgeon's actual needs.

[0026] The internal fixation system includes, but is not limited to, a locking and pressurizing steel plate system and a 3D-printed personalized steel plate system.

[0027] Preferably, the Tomofix locking pressure plate system is used for internal fixation.

[0028] (4) Close the incision and determine whether to place a drainage tube based on the actual situation. If there is no obvious bleeding or oozing, a drainage tube may not be placed.

[0029] The essential features of this invention are:

[0030] This invention designs a cement-aggregate-fiber three-component composite structure with good strength and collapse resistance, and achieves a soft-hard transformation through in-situ self-curing of the adhesive by absorbing water. Polyethylene glycol, as a plasticizer, gives the material excellent workability, ensuring that it can be arbitrarily shaped before surgery and that its strength gradually increases after surgery, providing mechanical support to the defect site. In simple terms, polyethylene glycol of different molecular weights is highly sensitive to temperature after being melted and mixed. Before surgery, it can be shaped by repeatedly kneading it in the hand. During surgery, after being packed into the bleeding wound, the hydrophilic polyethylene glycol and starch promote the entry of water molecules from the blood into the material, providing reaction conditions for the bone cement powder, which gradually solidifies and provides mechanical support for the defect. Functional aggregates, as the dispersed phase in the bone cement binder matrix, can significantly enhance the compressive strength and stability of the material. They can also be used as drug carriers for filling osteotomy gaps under special conditions, such as loading antibacterial drugs for filling osteotomy gaps with high infection risk or for reoperation after infection, and loading anti-osteoporosis drugs or osteogenic inducing factors for the treatment of patients with abnormal bone metabolism. Starch promotes hemostasis through its water absorption and coagulation functions. On the other hand, it forms a cement-aggregate-fiber structure similar to fiber-reinforced concrete with bone cement and aggregate particles, improving the mechanical strength and collapse resistance of the material. Postoperatively, the bone repair system, composed of polyethylene glycol that degrades rapidly within 5 days, aggregate particles with a relatively fast degradation rate, and bone cement with an extremely slow degradation rate, can achieve gradient degradation, ensuring new bone replacement and long-term bone healing.

[0031] The present invention has the following beneficial effects:

[0032] 1. The packing material prepared in this invention achieves automatic conversion from a hemostatic material to an osteogenic scaffold through a premixed self-curing design, meeting the needs of both intraoperative blood loss and postoperative osteogenic formation in high tibial osteotomy. The premixed self-curing design allows the material to combine the shape adaptability of a soft material with the mechanical support of a rigid material.

[0033] 2. The filling material prepared by this invention has the characteristics of being ready to use (can be used directly after opening the package), being able to be kneaded at will, and not sticking to gloves compared with other artificial bones. It is convenient and easy to use during surgery and can be fully adapted to bone defects of different shapes in patients.

[0034] 3. The packing material prepared by this invention can be used to control bleeding from osteotomy wounds. During operation, it can be directly pressed or applied to the bleeding site to achieve rapid hemostasis, reducing the use of drainage tubes and the occurrence of incision complications. The product does not have the defects of bone wax hemostatic materials such as foreign body reaction and interference with bone healing.

[0035] 4. The filling material prepared by this invention can absorb water in situ, solidify, and harden, forming a cement-aggregate-fiber structure with good mechanical strength and anti-collapse properties (see appendix). Figure 1 The test results of the example samples confirmed that the addition of aggregate particles and starch effectively improved the system's anti-collapse properties, and the compressive strength was comparable to that of cancellous bone (4.56 MPa for the example samples), providing effective mechanical support in the lower limb osteotomy gap area. This is beneficial for patients undergoing high tibial osteotomy to achieve early ambulation and accelerate rehabilitation during the surgical period.

[0036] 5. The filling material prepared in this invention is mainly composed of active bioceramics, which has good osteoconductivity and biocompatibility, can achieve gradient degradation, ensure new bone replacement, and promote bone healing at the osteotomy gap.

[0037] 6. The filling material prepared by the present invention contains functional aggregate particles, which can be used as a drug carrier for filling osteotomy gaps under special conditions. It is suitable for patients with high risk of infection, reoperation after infection, abnormal bone metabolism, or difficulty in bone healing.

[0038] 7. The raw materials for the materials prepared by this invention are abundant, the preparation process is simple, the equipment requirements are low, and large-scale production can be easily achieved. Attached Figure Description

[0039] Figure 1 This is a schematic diagram illustrating the operation of the filler material obtained in Example 1 and a schematic diagram illustrating the evaluation of its collapse resistance.

[0040] Figure 2 The results show the biosafety verification of the filling material obtained in Example 1.

[0041] Figure 3 The results of in vitro and in vivo hemostasis experiments of the filling material obtained in Example 1 are shown.

[0042] Figure 4 The results are from in vitro and in vivo osteogenic experiments using the filling material obtained in Example 1. Detailed Implementation

[0043] The present invention will be further described below with reference to specific embodiments, but the embodiments do not limit the present invention in any way.

[0044] Example 1

[0045] 0.45g of calcium nitrate was added to 110g of deionized water and completely dissolved. Then, 22g of Waxy starch was added to the solution and stirred at 85°C until the starch was completely gelatinized to obtain a viscous liquid. The liquid was placed in a drying oven at 110°C and left to stand for 10 hours. The material was then removed, pulverized, and passed through a 60-mesh sieve to obtain modified Waxy starch.

[0046] To prepare the filler material, 0.145g of modified Waxy starch, 0.4g of rough-surfaced and cured calcium phosphate particles (particle size 200-300 μm, compressive strength 10 MPa), 0.4g of water-curable calcium phosphate bone cement powder (particle size 100-250 μm), and 0.05g of sodium dihydrogen phosphate were mixed evenly in a sealed container by shaking for 5 minutes. Then, 0.6g of molten polyethylene glycol (prepared by melting and mixing polyethylene glycol 1500 and polyethylene glycol 500 at 70°C for 1 hour) was added. After maintaining the temperature at 70°C for 1 hour, the mixture was stirred with a glass rod for 1 minute, cooled to room temperature for 10 minutes, and kneaded for 1 minute to obtain a dough-like filler material.

[0047] After high tibial osteotomy, the osteotomy area is slowly opened using an oscillating saw (until the desired opening angle is achieved). Filler material is then inserted into the osteotomy gap, ensuring complete filling of the bone defect and sealing for hemostasis. Fixation is achieved using the Tomofix locking compression plate system. The incision is closed; if there is no significant bleeding or oozing, drainage tubes may not be necessary. Postoperatively, patients are encouraged to begin partial weight-bearing exercises of the affected limb as early as possible, and full weight-bearing exercises as early as approximately two weeks postoperatively. The filling material in the tibial defect area can absorb water and harden in situ, providing additional mechanical support to the affected limb in conjunction with internal fixation, reducing the incidence of hinge fractures and loss of corrective angle.

[0048] Example 2

[0049] Mix 0.15g corn starch powder, 0.2g vancomycin-loaded calcium phosphate granules (5g vancomycin per 100g calcium phosphate, particle size 400-600μm, strength 10MPa, already solidified and non-reactive with water), 0.6g calcium phosphate bone cement powder (particle size 100-250μm, can solidify upon contact with water), and 0.15g disodium hydrogen phosphate in a sealed container and shake for 10 minutes until homogeneous. Then add 0.5g polyethylene glycol (made by melting and mixing polyethylene glycol 1500 and polyethylene glycol 500 at 80℃), and place at 80℃ for 30 minutes. After that, stir with a glass rod for 1 minute and cool at room temperature for 10 minutes. Finally, knead for 1 minute to form a dough-like filling material.

[0050] After opening the bone using an oscillating saw during a high tibial osteotomy, bone graft material is packed into the osteotomy space to ensure complete filling of the bone defect and hemostasis. The Tomofix locking compression plate system is used for fixation. The incision is closed; if there is no significant bleeding or oozing, drainage tubes are not necessary. Vancomycin-loaded calcium phosphate granules can release antibiotics at high local concentrations, exerting a strong anti-infective effect.

[0051] Example 3

[0052] 50g of sweet potato starch was stirred at 70℃ until the starch was completely gelatinized, resulting in a viscous liquid. This liquid was placed in a container and allowed to stand at 100℃ for 24 hours to obtain sweet potato starch colloid. The material was then removed and pulverized through a 60-mesh sieve to obtain sweet potato starch adhesive powder. This powder can absorb water to form sweet potato starch adhesive. 0.1g of sweet potato starch adhesive powder, 0.6g of active glass particles (particle size 100-200 micrometers, strength 20MPa), 0.2g of calcium silicate bone cement powder (particle size 100-250 micrometers, water-curable), and 0.2g of sodium dihydrogen phosphate were mixed evenly. Then, 0.7g of polyethylene glycol (made by melting and mixing polyethylene glycol 1500 and polyethylene glycol 500 at 70℃) was added, and the mixture was placed at 70℃ for 30 minutes. After that, it was manually stirred for 1 minute and cooled to room temperature for 10 minutes. Finally, it was kneaded for 1 minute to obtain a dough-like filling material.

[0053] After using an oscillating saw to open the osteotomy in a high tibial osteotomy, a 3D-printed, personalized plate system is used for fixation. Material is then packed into the osteotomy gap, ensuring complete filling of the bone defect and sealing for hemostasis. The incision is closed; if there is no significant bleeding or oozing, drainage tubes may not be necessary.

[0054] Example 1: Performance Testing and Results of Filler Materials

[0055] Figure 1 This is a schematic diagram illustrating the operation of the filler material obtained in Example 1 and a schematic diagram illustrating the evaluation of its collapse resistance. Figure 1 Image a shows the effect of the material of this invention after opening the packaging; it can be rubbed and stuffed freely without sticking to the hands. Figure 1 b is a photograph showing the disintegration of the material of this invention. Figure 1 c is a statistical chart of the material mass loss rate results of this invention. Figure 1 d is a statistical graph of the compressive strength of this invention. Detailed experiments and analysis are as follows:

[0056] Figure 1 The image shows the effect of maintaining the osteotomy height 'a' using an internal fixation system. After opening the packaging, the material of this invention can be rubbed and packed without sticking to the hands, demonstrating that the material has good operability and ready-to-use properties, and can easily complete intraoperative packing and hemostasis. Figure 1Using an internal fixation system to maintain the osteotomy height, b represents the macroscopic disintegration of materials with different proportions of aggregate particles in phosphate buffered solution (PBS). The results show that the best anti-disintegration ability can be obtained when the addition ratio of calcium phosphate cement and calcium phosphate aggregate particles is 1:1. Figure 1 The comparison of the anti-collapse properties of materials prepared with no starch, ordinary starch, and modified starch using an internal fixation system to maintain osteotomy height c represents the following. The filler materials with different starches were soaked in PBS for 10 minutes to quantitatively assess their mass loss. The mass loss was recorded after soaking the filler material in a culture dish (60 mm in diameter) containing 10 mL of PBS for 10 minutes. The specific mass loss statistics are as follows: (1) The mass of the filler material before being placed in PBS is recorded as M0. (2) At room temperature, the columnar filler material (6 mm in diameter and 12 mm in height) is placed in PBS. (3) After taking a picture, the column is removed and placed in a freeze dryer for 24 hours. (4) The freeze-dried mass is recorded as M1. Mass loss rate = (M0-M1) / M0. The experimental results show that the addition of modified starch can effectively improve the anti-collapse properties of the system. The compressive strength of the filler material was compared with that of columnar filler material (6 mm in diameter, 12 mm in height) without calcium phosphate aggregate particles after in-situ curing in PBS for 10 days. Axial compression tests were conducted using a universal testing machine with a 5 kN sensor at a rate of 50 mm / min. The results showed that the material in Example 1 achieved a compressive strength comparable to cancellous bone (4.56 MPa), and the addition of calcium phosphate aggregate particles significantly improved the compressive strength. These results confirm the roles of aggregate particles and starch fiber in the cement-aggregate-fiber structural system; that is, aggregate particles can effectively improve the system's resistance to disintegration and compressive strength after curing, while starch can effectively mitigate the system's mass loss.

[0057] Figure 2 The results of the biosafety verification of the filler material of the present invention are as follows: Figure 2 In this context, 'a' indicates that the hemolysis rate of this invention is 3%, which is lower than the standard requirement of 5%. Figure 2 Using an internal fixation system to maintain the osteotomy height b, the CCK-8 test results for this invention all showed no cytotoxicity. Detailed experiments and analyses are as follows:

[0058] To ensure the biocompatibility of this invention, the hemolysis rate of the material was evaluated according to national standards YY-T01271-1993 and GB / T16886.12-2005, and cytotoxicity tests (CCK-8) were performed on the material extract at 1 and 3 days. Figure 2As shown in Figure a, the hemolysis rate was 0% in the saline group (negative control group), 100% in the distilled water group (positive control group), and less than 3% in both commercially available medical bone wax and filler materials. The standard stipulates that a hemolysis rate of less than 5% is considered as no significant hemolysis. (CCK-8 test results) Figure 2 (b) Neither experimental group showed a significant impact on cell viability. The filling material does not produce hemolysis or cytotoxicity, which improves its feasibility as a hemostatic filling material for bone hemorrhage.

[0059] Figure 3 The results of in vitro and in vivo hemostasis experiments on the filling material of this invention are as follows: Figure 3 In this context, 'a' indicates that the in vitro coagulation index of this invention (0.1579±0.075) is significantly superior to that of commercially available bone wax (0.38±0.22). Figure 3 In the figure, 'b' represents the statistical analysis of the in vivo hemostasis effect using a rat femoral defect animal model in this invention. The blood loss in the filling material group was only 0.067±0.023g. Detailed experiments and analyses are as follows:

[0060] In vitro hemostasis test: Commercially available medical bone wax and filler material were placed in a serum bottle (no sample was found in the control group). The bottle was then preheated at 37°C for 30 minutes. 1 mL of anticoagulated rabbit whole blood was mixed with 0.1 mL of 0.1 M CaCl2 solution and slowly dripped onto the sample surface. After 5 minutes, 3 mL of deionized water was added along the bottle wall. Then, 2 mL of the solution was removed, and its relative absorbance at 540 nm was measured; this was the coagulation index. Figure 3 As can be seen from this, the in vitro coagulation index of this invention (0.1579±0.075) is significantly better than that of commercially available bone wax (0.38±0.22) (the lower the coagulation index, the better the effect). The in vitro coagulation effect of the filling material is superior to that of commercially available medical bone wax.

[0061] In vivo hemostasis experiment (rat femoral defect animal model): Several sterile, dry cotton balls were weighed before surgery and recorded as M0. After penetrating the femoral cortex, commercially available medical bone wax or filling material was immediately used to stop the bleeding. Exudate was continuously wiped away with dry cotton balls for 5 minutes, and the mass of the cotton balls was recorded as M1. The bleeding volume of the rat femoral defect was determined using the difference method: M = M1 - M0. The ratio (relative blood loss) was obtained by dividing the obtained M by the mass of the rat used. Animal bone hemostasis sealing experiments have always been the gold standard for evaluating bone hemostasis. Results are as follows... Figure 3 b. The blood loss from the filling material was significantly different from that of the control group. In rats that were not treated with the material within 5 minutes, the blood loss was as high as 0.95±0.37g of body weight. However, when the filling material was used to seal the bleeding site in the femur of the rats immediately, the final blood loss was only 0.067±0.023g of body weight, which was significantly lower than that of the control group and met the clinical hemostasis requirements.

[0062] Figure 4The results of in vitro and in vivo osteogenic experiments using the filling material obtained in Example 1 are shown below. Figure 4 In the image, 'a' represents an Alizarin Red S staining image of MC3T3-E1 osteoblasts on day 14 in an in vitro osteogenic experiment (the white arrow indicates the calcium nodules). Figure 4 Figure b shows a comparison of bone repair after one month of in vivo osteogenic experiments using a rat skull defect animal model. The experiment and detailed analysis are as follows:

[0063] In vitro osteogenic assay (Alizarin Red S staining): 100,000 cells were seeded in sterile 6-well plates, 3 wells per group. After cell adhesion, 2 mL of extraction buffer or osteogenic induction medium was added to each well for induction. After osteogenic differentiation was induced in osteogenic medium for 2 weeks, Alizarin Red S staining was used to detect the formation of calcium deposits or calcium nodules. The culture medium was carefully removed, taking care not to aspirate the cells. Preheated sterile PBS solution was slowly added along the plate to wash the cells three times. The cells were fixed with anhydrous ethanol at room temperature for 30 min, then gently rinsed three times with distilled water for 5 min each time, taking care not to agitate the cells. 2 mL of Alizarin Red S staining solution was added to each well, and the plates were incubated at room temperature for 20 min. The cells were then gently washed with distilled water, taking care not to shake the culture dish to prevent the formation of calcium deposits from being detached. Calcium-containing mineralized nodules were stained red spots by Alizarin Red S staining solution. These were observed and photographed under a bright-field optical microscope. Figure 4 The filling material group showed more calcium nodules compared to other groups, which is a strong osteogenic phenomenon.

[0064] In vivo osteogenesis experiment (rat skull defect animal model): A 3cm longitudinal incision was made in the rat skull, cutting through the skin, subcutaneous tissue, and muscle-periosteal layer, and flaps were turned up. The skull plates were bluntly dissected to expose the bone plates. Two circular, full-thickness periosteal bone defects, each 5mm in diameter, were created on both sides of the midcranial suture using a hand drill with a 5mm outer diameter trephine. Pre-prepared material was filled into the defects, while the control group retained the defects without filling. The incision was closed and sutured layer by layer. One month post-surgery, the rats were sacrificed, and the skulls were removed for imaging evaluation using Micro-CT. The results showed that the control and bone wax groups retained well-defined, round bone defects with insufficient bone ingrowth. In contrast, the filling material group showed blurred defect edges, significant bone ingrowth, and new bone tissue mixed with undegraded material forming in the center of the defect, demonstrating the in vivo osteogenic capacity of the filling material.

[0065] As can be seen from the above embodiments, this invention focuses on improving the hemostatic ability and operability of the material. Aggregate particles are introduced as the dispersed phase, forming a cement-aggregate-fiber composite structure together with calcium phosphate and starch to improve the material's mechanical strength and anti-collapse properties. Polyethylene glycol is used as a water absorbent and plasticizer to bind the above components together, forming a premixed, self-curing, soft solid material. This material can be conveniently filled into the osteotomy gap during surgery to seal the osteotomy surface for hemostasis, and it absorbs water and cures in situ, providing strength support as artificial bone and promoting interstitial bone healing.

[0066] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. However, the above description is merely a specific embodiment of the present invention, and the technical features of the present invention are not limited thereto. Any other embodiments derived by those skilled in the art without departing from the technical solution of the present invention should be covered within the patent scope of the present invention.

[0067] Matters not covered in this invention are common knowledge.

Claims

1. A method for preparing a gap-filling material for high tibial osteotomy, characterized in that the method includes the following steps: (1) Take 30-50 parts of bio-bone cement powder, 30-50 parts of functional aggregate particles, 5-20 parts of starch powder and 0-2 parts of phosphate and add them into a container. Seal and shake to mix. (2) In a water bath at 60-100℃, melt 40-80 parts of polyethylene glycol and add it to the container in step (1). Continue heating for 0.5-2 hours, stir for 0.5-2 minutes to form a mixture, and then cool to room temperature. Knead for 1-2 minutes to form a dough-like consistency to obtain the osteotomy gap filling material of the present invention for high tibial osteotomy. The phosphate mentioned is sodium dihydrogen phosphate; The bio-bone cement powder mentioned above is calcium phosphate bone cement powder. The functional aggregate particles are calcium phosphate ceramic particles; The starch powder is modified Waxy starch. The preparation of the modified Waxy starch includes: adding 0.45g of calcium nitrate to 110g of deionized water and dissolving it completely, then adding 22g of Waxy starch to the above solution, stirring at 85°C until the starch is completely gelatinized to obtain a viscous liquid, placing it in a drying oven at 110°C and letting it stand for 10 hours, taking out the material and pulverizing it through a 60-mesh sieve to obtain modified Waxy starch; The polyethylene glycol mentioned includes polyethylene glycol 1500 and polyethylene glycol 500; The compressive strength of calcium phosphate ceramic particles is 2-100 MPa.

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