Preparation method of an implantable auricular cartilage composite scaffold

Abstract

The present invention discloses a preparation method for an implantable ear cartilage composite scaffold, which belongs to the technical field of medical biomaterial preparation. The implantable ear cartilage composite scaffold includes an ultra-high molecular weight polyethylene porous composite scaffold and a low-density polyethylene sheet; the ultra-high molecular weight polyethylene composite scaffold is composed of ultra-high molecular weight polyethylene particles as a matrix, and nano-hydroxyapatite is doped to improve the mechanical properties of the material and improve its hydrophilicity; the ultra-high molecular weight polyethylene composite porous scaffold is prepared by a hot pressing and sintering method; the present invention uses a melt bonding method to cover the low-density polyethylene sheet on the surface of the composite porous scaffold to enhance the tensile strength and toughness of the composite porous scaffold; the ear cartilage composite scaffold prepared by the present invention has personalized characteristics and good biological activity, the scaffold has a three-dimensional interconnected macroporous structure, and the internal pore size distribution range is wide, which meets the conditions for cell attachment and tissue growth; the preparation method of the present invention is simple and effective.

Description

Technical Field

[0001] The present invention relates to a preparation method of an implantable ear cartilage composite scaffold, belonging to the technical field of medical biomaterial preparation Background Art

[0002] Auricle defects or loss due to various reasons such as congenital microtia, trauma and tumors are common in clinical practice. The auricle is one of the main features of the human face, and its defect or loss will seriously affect the patient's aesthetic and mental health. The human auricle is mainly composed of two tissues: skin and cartilage. Since skin tissue can be easily obtained through local skin expansion and / or skin grafting, the key difficulty in ear reconstruction for auricle defects lies in how to obtain an ear reconstruction scaffold with good morphology and function. Due to the advantages of high-density polyethylene (HDPE) such as good biocompatibility, plasticity, chemical stability and excellent mechanical properties, high-density polyethylene (MEDPOR) formed by hot compression molding is currently widely used as auricle repair material. However, its disadvantages are insufficient mechanical strength and the need to improve hydrophilicity. There is an urgent need to develop an ear reconstruction scaffold with normal physiological functions and that meets actual needs.

[0003] Chinese patent CN113693781A discloses a composite artificial scaffold for full auricle reconstruction and a method for its preparation. This method provides a method for casting a layer of silicone body on the surface of a memory alloy scaffold, which enables the scaffold to have good recovery performance and good biocompatibility. However, the surface of this patent is cast with silicone, and the scaffold surface has no porous structure, which makes it difficult for cells to attach and grow on the scaffold surface, making it difficult for vascularization to occur, and the scaffold is easily exposed due to external forces. Chinese patent CN20131002132 discloses a silk fibroin cartilage composite artificial ear and a method for its preparation. A composite scaffold is prepared by combining silk fibroin with chondrocytes. The mechanical strength of the scaffold prepared by this method is too low to maintain the three-dimensional shape of the auricle for a long time, and the implantation effect is poor. The chondrocyte culture transmission time is long, and the operation time is difficult to control specifically. Summary of the Invention

[0004] In order to solve the deficiencies in the prior art, the present invention aims to provide a method for preparing an implantable ear cartilage composite scaffold. The specific preparation steps are as follows:

[0005] (1) Ultra-high molecular weight polyethylene particles and hydroxyapatite powder are added to an ethanol solution (the ethanol is sufficient to completely cover the solid powder) and mixed evenly by ball milling. The mixture is then dried at room temperature (there is no special requirement for the room temperature here, and conventional room temperature can be used) to obtain a composite powder for preparing an ultra-high molecular weight porous composite scaffold.

[0006] (2) The composite powder obtained in step (1) is placed in a special polytetrafluoroethylene mold, fully shaken and then fixed, and pre-pressed. After cooling, an ultra-high molecular weight polyethylene composite sheet is obtained.

[0007] (3) hot-pressing and sintering the ultra-high molecular weight polyethylene composite sheet obtained after the pre-pressing treatment in step (2), and cooling it to room temperature to obtain an ultra-high molecular weight polyethylene matrix material.

[0008] (4) Soaking the ultra-high molecular weight polyethylene matrix material obtained in step (3) in a mixed solution of concentrated sulfuric acid and hydrogen peroxide for 10 min to 15 min.

[0009] (5) The low-density polyethylene powder is placed in a homemade mold and vibrated and compacted. The mold is then placed in a high-temperature device for melting. The resulting low-density polyethylene molten liquid is poured out and quickly and evenly flattened before solidification. Low-density polyethylene sheets with uniform thickness are obtained through trimming and polishing.

[0010] (6) The ultra-high molecular weight polyethylene matrix material treated with a mixed solution of concentrated sulfuric acid and hydrogen peroxide in step (4) is laminated with the surface of the low-density polyethylene sheet obtained in step (5) and then loaded into a special polytetrafluoroethylene mold. The mold is then placed in a sintering device and heated to melt the contact surfaces of the two so as to bond them together. After cooling, the mold is placed in an ethanol solution for cleaning.

[0011] Preferably, the particle size of the ultra-high molecular weight polyethylene particles in step (1) is between 10 mesh and 100 mesh, and the molecular weight is between 150w and 1000w.

[0012] More preferably, the particle size of the ultra-high molecular weight polyethylene particles in step (1) is between 30 mesh and 40 mesh.

[0013] Preferably, the mass percentage of the nano-hydroxyapatite added in step (1) is 0-20% of the ultra-high molecular weight polyethylene particles, and the hydroxyapatite is in nano or micro state.

[0014] Preferably, the heating rate of the pre-pressing treatment in step (2) is 5°C / min-10°C / min, the temperature is 150°C, the pressure is 10 MPa, and the treatment time is 5 min-15 min.

[0015] More preferably, the heating rate of the pre-pressing treatment in step (2) is 10°C / min, and the treatment time is 10 min.

[0016] Preferably, the heating rate of hot pressing sintering in step (3) is 5°C / min-10°C / min, the temperature is 165°C-200°C, the pressure is 5 MPa, the sintering time is 10 min-30 min, and the thickness of the prepared ultra-high molecular weight polyethylene matrix material is 0.5 mm-5 mm, and the internal pore diameter is 50 μm-200 μm.

[0017] More preferably, the heating rate of the hot pressing sintering in step (3) is 10° C. / min, the sintering time is 20 min, and the internal pore diameter is 50 μm-150 μm.

[0018] Preferably, in step (4), the volume ratio of concentrated sulfuric acid to hydrogen peroxide is 1:1, wherein the mass fraction of concentrated sulfuric acid used is (1.84 g / ml).

[0019] Preferably, in step (5), the heating rate is 5°C / min-10°C / min, the melting temperature is 150°C-170°C, the melting time is 10min-15min, and the thickness of the prepared low-density polyethylene sheet is 0.2mm-0.5mm.

[0020] More preferably, in step (5), the melting temperature is 170° C. and the melting time is 10 min.

[0021] Preferably, the mold in step (5) is a stainless steel hollow cylindrical mold, which can be clamped by tongs.

[0022] Preferably, the molds in step (2) and step (6) are specially made polytetrafluoroethylene molds, which are divided into a solid positive mold and a solid negative mold. The interior of the solid negative mold is a hollow part of 4cm×4cm×1cm, and the solid negative mold and the solid positive mold can fit tightly.

[0023] Preferably, in step (6), the sintering temperature is 100° C.-180° C., and the sintering time is 5 min-8 min.

[0024] More preferably, in step (6), the sintering temperature is 150° C. and the sintering time is 5 minutes.

[0025] Beneficial effects of the present invention

[0026] (1) The contact angle of the surface of the ultra-high molecular weight polyethylene matrix material of the ear cartilage composite scaffold of the present invention is significantly reduced after being treated with a mixed solution of concentrated sulfuric acid and hydrogen peroxide, showing hydrophilicity, which is conducive to cell adhesion and growth.

[0027] (2) The spherical ultra-high molecular weight polyethylene particles used in the ear cartilage composite scaffold of the present invention have the characteristics of uniform morphology and appropriate molecular weight. The spherical ultra-high molecular weight polyethylene particles are used to prepare the ear cartilage composite scaffold through powder sintering technology. The microscopic morphology of the composite scaffold can be theoretically explained by combining the most compact model of medium-large spheres in the crystal structure: the internal pore size of the ear cartilage composite scaffold is affected by the initial morphology of the particles. By changing the sintering parameters, the internal structure of the ear cartilage composite scaffold can be controlled, thereby obtaining an ear cartilage composite scaffold with a porosity and pore size distribution suitable for cell adhesion and tissue growth.

[0028] (3) The ear cartilage composite scaffold of the present invention is composed of an ultra-high molecular weight polyethylene porous scaffold and a low-density polyethylene sheet. The ultra-high molecular weight polyethylene porous scaffold provides appropriate mechanical strength, and its three-dimensional porous structure provides favorable conditions for cell attachment and growth as well as vascularization of surrounding tissues. The low-density polyethylene material has good softness, ductility, and ease of processing. By combining it with the low-density polyethylene sheet, the mechanical properties of the composite scaffold can be enhanced, thereby preventing the scaffold from being subjected to external forces after implantation into the body and causing further implantation failure.

[0029] (4) The porosity, surface morphology and pore size distribution of the ultra-high molecular weight polyethylene matrix material in the ear cartilage composite scaffold described in the present invention can be determined by the sintering parameters. During the sintering process, ultra-high molecular weight polyethylene particles produce a sintering neck due to chain diffusion. The length of the sintering neck is a function of the sintering temperature and time, and affects the mechanical properties and microstructure of the material. Increasing the sintering temperature and extending the sintering time can increase the length of the sintering neck, thereby improving the mechanical properties of the porous scaffold, but at the same time it will also reduce the porosity and pore size distribution of the porous scaffold. The porous material prepared by the present invention using appropriate sintering parameters has a porosity suitable for cell attachment and tissue growth, and the mechanical properties meet surgical requirements. The prepared scaffold material can be personalized according to the actual situation of the patient and has strong practical operability.

[0030] (5) The implantable ear cartilage composite scaffold prepared by the present invention has good biocompatibility and has no obvious immune rejection reaction after implantation in the body.

[0031] (6) The implantable ear cartilage composite scaffold prepared by the present invention has a mechanical strength similar to that of auricular cartilage, meeting the requirement of maintaining a three-dimensional shape for a long time while avoiding exposure of the scaffold due to external forces.

[0032] (7) The implantable ear cartilage composite scaffold prepared by the present invention has a certain three-dimensional porous structure. The porous structure is suitable for cell attachment and growth, and can undergo a certain degree of vascularization with the surrounding tissues, thereby improving the biocompatibility of the scaffold. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is a scanning electron microscope image of spherical ultra-high molecular weight polyethylene particles;

[0034] Figure 2 This is a scanning electron microscope image of the porous structure of the ultra-high molecular weight polyethylene particles sintered at 200°C in Example 4;

[0035] Figure 3 This is a scanning electron microscope image of the porous structure inside the material of the ultra-high molecular weight polyethylene particles in Example 1 when sintered at 185°C. DETAILED DESCRIPTION

[0036] The present invention will be further described in detail below with reference to specific embodiments, but the protection scope of the present invention is not limited to the contents described above.

[0037] The specially made polytetrafluoroethylene mold used in all embodiments is divided into a solid male mold and a solid female mold. The interior of the solid female mold is a hollow part of 4 cm×4 cm×1 cm. The solid female mold and the solid male mold can fit tightly.

[0038] Example 1

[0039] Preparation of an implantable ear cartilage composite scaffold, the specific steps are as follows

[0040] (1) 1.2 g of ultra-high molecular weight polyethylene spherical particles with an average particle size of 30 mesh and 0.12 g of hydroxyapatite particles were mixed, and ethanol was added to cover the solid particles. The mixture was uniformly mixed using a high-speed ball mill at a speed of 500 r / min, and dried at room temperature to obtain a composite powder for preparing an ultra-high molecular weight porous composite scaffold.

[0041] (2) The composite powder obtained in step (1) is placed in a special polytetrafluoroethylene mold, shaken thoroughly and fixed, and placed in a sintering device for pre-pressing treatment with a heating rate of 10°C / min, a pre-pressing sintering temperature of 150°C, a pre-pressing sintering time of 10 min, and a pre-pressing pressure of 10 MPa; and after cooling at room temperature, an ultra-high molecular weight polyethylene composite sheet is obtained.

[0042] (3) The high molecular weight polyethylene composite sheet obtained in step (2) is again loaded into a special polytetrafluoroethylene mold for sintering treatment, and the heating rate is set to 10°C / min, the sintering temperature is 185°C, and the pressure is 5 MPa. After sintering for 20 minutes, an ultra-high molecular weight polyethylene porous scaffold is obtained.

[0043] (4) The ultra-high molecular weight polyethylene porous scaffold obtained in step (3) is immersed in a mixed solution of concentrated sulfuric acid and hydrogen peroxide in a volume ratio of 1:1 for surface treatment.

[0044] (5) The low-density polyethylene powder was placed in a mold and vibrated and compacted. The mold was then placed in a high-temperature device and heated to 170°C at a rate of 5°C / min. The melted low-density polyethylene liquid was poured out and quickly and evenly flattened before solidification. The mold was trimmed and polished to obtain a 0.5 mm thick and 4*4 (cm 2 ) of low-density polyethylene sheet.

[0045] (6) The ultra-high molecular weight polyethylene porous scaffold obtained by the treatment in step (4) is tightly fitted with the low-density polyethylene sheet obtained in step (5) and then loaded into a special polytetrafluoroethylene mold. The mold is placed in a sintering device and heated at 150°C for 5 minutes to melt the contact surfaces of the two and thus bond them together. After cooling, the mold is placed in an ethanol solution for cleaning to obtain an implantable ear cartilage composite scaffold.

[0046] Figure 3 This is a scanning electron microscope image of the porous structure of ultra-high molecular weight polyethylene particles sintered at 185°C. Figure 3 It can be seen that the particles are arranged in a face-centered cubic pattern. The scaffold prepared by powder sintering has a porous structure. The pore size in the figure can be between 50μm and 150μm, which is suitable for cell attachment and tissue growth.

[0047] Example 2

[0048] Preparation of an implantable ear cartilage composite scaffold, the specific steps are as follows

[0049] (1) 1.2 g of ultra-high molecular weight polyethylene spherical particles with an average particle size of 40 mesh and 0.12 g of hydroxyapatite particles were mixed, and ethanol was added to cover the solid particles. The mixture was uniformly mixed using a high-speed ball mill at a speed of 500 r / min, and dried at room temperature to obtain a composite powder for preparing an ultra-high molecular weight porous composite scaffold.

[0050] (2) The composite powder obtained in step (1) is placed in a special polytetrafluoroethylene mold, shaken thoroughly and fixed, and placed in a sintering device for pre-pressing treatment with a heating rate of 10°C / min, a pre-pressing sintering temperature of 150°C, a pre-pressing sintering time of 10 min, and a pre-pressing pressure of 10 MPa; and after cooling at room temperature, an ultra-high molecular weight polyethylene composite sheet is obtained.

[0051] (3) The high molecular weight polyethylene composite sheet obtained in step (2) is again loaded into a special polytetrafluoroethylene mold for sintering treatment, and the heating rate is set to 10°C / min, the sintering temperature is 185°C, and the pressure is 5 MPa. After sintering for 20 minutes, an ultra-high molecular weight polyethylene porous scaffold is obtained.

[0052] (4) The ultra-high molecular weight polyethylene porous scaffold obtained in step (3) is immersed in a mixed solution of concentrated sulfuric acid and hydrogen peroxide in a volume ratio of 1:1 for surface treatment.

[0053] (5) The low-density polyethylene powder was placed in a mold and vibrated and compacted. The mold was then placed in a high-temperature device and heated to 170°C at a rate of 5°C / min. The melted low-density polyethylene liquid was poured out and quickly and evenly flattened before solidification. The mold was trimmed and polished to obtain a 0.5 mm thick and 4*4 (cm 2 ) of low-density polyethylene sheet.

[0054] (6) The ultra-high molecular weight polyethylene porous scaffold obtained by the treatment in step (4) is tightly fitted with the low-density polyethylene sheet obtained in step (5) and then loaded into a special polytetrafluoroethylene mold. The mold is placed in a sintering device and heated at 150°C for 5 minutes to melt the contact surfaces of the two and thus bond them together. After cooling, the mold is placed in an ethanol solution for cleaning to obtain an implantable ear cartilage composite scaffold.

[0055] Example 3

[0056] (1) 1.2 g of ultra-high molecular weight polyethylene spherical particles with an average particle size of 30 mesh and 0.2 g of hydroxyapatite particles were mixed, and ethanol was added to cover the solid particles. The mixture was uniformly mixed using a high-speed ball mill at a speed of 500 r / min, and dried at room temperature to obtain a composite powder for preparing an ultra-high molecular weight porous composite scaffold.

[0057] (2) The composite powder obtained in step (1) is placed in a special polytetrafluoroethylene mold, shaken thoroughly and fixed, and placed in a sintering device for pre-pressing treatment with a heating rate of 10°C / min, a pre-pressing sintering temperature of 150°C, a pre-pressing sintering time of 10 min, and a pre-pressing pressure of 10 MPa; and after cooling at room temperature, an ultra-high molecular weight polyethylene composite sheet is obtained.

[0058] (3) The high molecular weight polyethylene composite sheet obtained in step (2) is again loaded into a special polytetrafluoroethylene mold for sintering treatment, and the heating rate is set to 10°C / min, the sintering temperature is 165°C, and the pressure is 5 MPa. After sintering for 20 minutes, an ultra-high molecular weight polyethylene porous scaffold is obtained.

[0059] (4) The ultra-high molecular weight polyethylene porous scaffold obtained in step (3) was immersed in a mixed solution of concentrated sulfuric acid and hydrogen peroxide with a volume ratio of 1:1 for surface treatment for 10 minutes.

[0060] (5) Low-density polyethylene powder was placed in a mold and vibrated and compacted. The mold was then placed in a high-temperature device and heated to 170°C at a rate of 5°C / min. The melted low-density polyethylene liquid was poured out and quickly and evenly flattened before solidification. After trimming and polishing, a 0.2 mm thick and 4*4 (cm2) area was obtained. 2 ) of low-density polyethylene sheet.

[0061] (6) The ultra-high molecular weight polyethylene porous scaffold obtained by the treatment in step (4) is tightly fitted with the low-density polyethylene sheet obtained in step (5) and then loaded into a special polytetrafluoroethylene mold. The mold is placed in a sintering device and heated at 159°C for 5 minutes to melt the contact surfaces of the two and thus bond them together. After cooling, the mold is placed in an ethanol solution for cleaning to obtain an implantable ear cartilage composite scaffold.

[0062] Example 4

[0063] (1) 1.2 g of ultra-high molecular weight polyethylene spherical particles with an average particle size of 30 mesh and 0.15 g of hydroxyapatite particles were mixed, and ethanol was added to cover the solid particles. The mixture was uniformly mixed using a high-speed ball mill at a speed of 500 r / min, and dried at room temperature to obtain a composite powder for preparing an ultra-high molecular weight porous composite scaffold.

[0064] (2) The composite powder obtained in step (1) is placed in a special polytetrafluoroethylene mold, shaken thoroughly and fixed, and placed in a sintering device for pre-pressing treatment with a heating rate of 10°C / min, a pre-pressing sintering temperature of 150°C, a pre-pressing sintering time of 10 min, and a pre-pressing pressure of 10 MPa; and after cooling at room temperature, an ultra-high molecular weight polyethylene composite sheet is obtained.

[0065] (3) The high molecular weight polyethylene composite sheet obtained in step (2) is again loaded into a special polytetrafluoroethylene mold for sintering treatment, and the heating rate is set to 10°C / min, the sintering temperature is 200°C, and the pressure is 5 MPa. After sintering for 20 minutes, an ultra-high molecular weight polyethylene porous scaffold is obtained.

[0066] (4) The ultra-high molecular weight polyethylene porous scaffold obtained in step (3) was immersed in a mixed solution of concentrated sulfuric acid and hydrogen peroxide with a volume ratio of 1:1 for surface treatment for 10 minutes.

[0067] (5) Low-density polyethylene powder was placed in a mold and vibrated and compacted. The mold was then placed in a high-temperature device and heated to 170°C at a rate of 10°C / min. The melted low-density polyethylene liquid was poured out and quickly and evenly flattened before solidification. After trimming and polishing, a 0.5 mm thick and 4*4 (cm2) area was obtained. 2 ) of low-density polyethylene sheet.

[0068] (6) The ultra-high molecular weight polyethylene porous scaffold obtained by the treatment in step (4) is tightly fitted with the low-density polyethylene sheet obtained in step (5) and then loaded into a special polytetrafluoroethylene mold. The mold is placed in a sintering device and heated at 150°C for 5 minutes to melt the contact surfaces of the two and thus bond them together. After cooling, the mold is placed in an ethanol solution for cleaning to obtain an implantable ear cartilage composite scaffold.

[0069] Figure 2 This is a scanning electron microscope image of the porous structure of ultra-high molecular weight polyethylene particles sintered at 200°C. Figure 2 It can be seen that as the sintering temperature is increased, the particles come into contact with each other, and larger sintering necks appear between the particles after sintering, thereby providing stronger mechanical strength.

[0070] Example 5

[0071] (1) 1.2 g of ultra-high molecular weight polyethylene spherical particles with an average particle size of 30 mesh were added to ethanol to cover the solid particles, and mixed evenly at a speed of 500 r / min using a high-speed ball mill. After drying at room temperature, an ultra-high molecular weight powder was obtained.

[0072] (2) The powder obtained in step (1) is placed in a special polytetrafluoroethylene mold, shaken thoroughly and fixed, and placed in a sintering device for pre-pressing treatment with a heating rate of 10°C / min, a pre-pressing sintering temperature of 150°C, a pre-pressing sintering time of 10 min, and a pre-pressing pressure of 10 MPa; and an ultra-high molecular weight polyethylene sheet is obtained after cooling at room temperature.

[0073] (3) The high molecular weight polyethylene sheet obtained in step (2) was again loaded into a special polytetrafluoroethylene mold for sintering treatment, with a heating rate of 10°C / min, a sintering temperature of 185°C, and a pressure of 5 MPa. After sintering for 20 minutes, an ultra-high molecular weight polyethylene porous scaffold was obtained.

[0074] (4) The ultra-high molecular weight polyethylene porous scaffold obtained in step (3) is immersed in a mixed solution of concentrated sulfuric acid and hydrogen peroxide in a volume ratio of 1:1 for surface treatment.

[0075] (5) The low-density polyethylene powder was placed in a mold and vibrated and compacted. The mold was then placed in a high-temperature device and heated to 170°C at a rate of 5°C / min. The melted low-density polyethylene liquid was poured out and quickly and evenly flattened before solidification. The mold was trimmed and polished to obtain a 0.5 mm thick and 4*4 (cm 2 ) of low-density polyethylene sheet.

[0076] (6) The ultra-high molecular weight polyethylene porous scaffold obtained by the treatment in step (4) is tightly fitted with the low-density polyethylene sheet obtained in step (5) and then loaded into a special polytetrafluoroethylene mold. The mold is placed in a sintering device and heated at 150°C for 5 minutes to melt the contact surfaces of the two and thus bond them together. After cooling, the mold is placed in an ethanol solution for cleaning to obtain an implantable ear cartilage composite scaffold.

[0077] Comparative Example 1

[0078] For comparison, the only difference between this comparative example and Example 1 is that the surface treatment of the ultra-high molecular weight polyethylene porous scaffold with a mixed solution of concentrated sulfuric acid and hydrogen peroxide in a volume ratio of 1:1 in step (4) is omitted. The other steps are the same as those in Example 1, specifically:

[0079] (1) 1.2 g of ultra-high molecular weight polyethylene spherical particles with a particle size of 30 mesh and a molecular weight of 300w and 0.12 g of nano-hydroxyapatite particles were mixed, and anhydrous ethanol was added until the solid particles were covered with anhydrous ethanol. The mixture was uniformly mixed using a high-speed ball mill at a speed of 500 r / min, and dried at room temperature to obtain a composite powder for preparing an ultra-high molecular weight porous composite scaffold.

[0080] (2) The composite powder obtained in step (1) is placed in a special polytetrafluoroethylene mold, shaken thoroughly and fixed, and placed in a sintering device for pre-pressing treatment with a heating rate of 10°C / min, a pre-pressing sintering temperature of 150°C, a pre-pressing sintering time of 10 min, and a pre-pressing pressure of 10 MPa; and after cooling at room temperature, an ultra-high molecular weight polyethylene composite sheet is obtained.

[0081] (3) The high molecular weight polyethylene composite sheet obtained in step (2) is again loaded into a special polytetrafluoroethylene mold for sintering treatment, and the heating rate is set to 10°C / min, the sintering temperature is 185°C, and the pressure is 5 MPa. After sintering for 20 minutes, an ultra-high molecular weight polyethylene porous scaffold is obtained.

[0082] (4) 0.12 g of low-density polyethylene powder was placed in a stainless steel hollow cylindrical mold with a diameter of 10 cm and a height of 6 cm and vibrated and compacted. The mold was then placed in a high-temperature device and heated to 170°C at a rate of 5°C / min. The melted low-density polyethylene liquid was poured out and quickly and evenly flattened before solidification. After trimming and polishing, a 0.5 mm thick and 4*4 (cm2) area was obtained. 2 ) of low-density polyethylene sheet.

[0083] (5) The ultra-high molecular weight polyethylene porous scaffold obtained in step (3) is tightly fitted with the low-density polyethylene sheet obtained in step (4) and then loaded into a special tetrafluoroethylene mold. The mold is placed in a sintering device and heated at 170°C for 5 minutes to melt the contact surfaces of the two and thus bond them together. After cooling, the mold is placed in an anhydrous ethanol solution for cleaning to obtain an implantable ear cartilage composite scaffold.

[0084] Comparative Example 2

[0085] For comparison, the only difference between this comparative example and Example 1 is that ultra-high molecular weight polyethylene powder is used in step (1), and the other steps are the same as those in Example 1, specifically:

[0086] (1) 1.2 g of ultra-high molecular weight polyethylene spherical powder and 0.12 g of nano-hydroxyapatite particles were mixed, anhydrous ethanol was added until the solid particles were covered by the anhydrous ethanol, and the mixture was uniformly mixed at a speed of 500 r / min using a high-speed ball mill. After drying at room temperature, a composite powder for preparing an ultra-high molecular weight porous composite scaffold was obtained.

[0087] (2) The composite powder obtained in step (1) is placed in a special polytetrafluoroethylene mold, shaken thoroughly and fixed, and placed in a sintering device for pre-pressing treatment with a heating rate of 10°C / min, a pre-pressing sintering temperature of 150°C, a pre-pressing sintering time of 10 min, and a pre-pressing pressure of 10 MPa; and after cooling at room temperature, an ultra-high molecular weight polyethylene composite sheet is obtained.

[0088] (3) The high molecular weight polyethylene composite sheet obtained in step (2) is again loaded into a special polytetrafluoroethylene mold for sintering treatment, and the heating rate is set to 10°C / min, the sintering temperature is 185°C, and the pressure is 5 MPa. After sintering for 20 minutes, an ultra-high molecular weight polyethylene porous scaffold is obtained.

[0089] (4) The ultra-high molecular weight polyethylene porous scaffold obtained in step (3) is immersed in a mixed solution of concentrated sulfuric acid and hydrogen peroxide in a volume ratio of 1:1 for surface treatment.

[0090] (5) 0.12 g of low-density polyethylene powder was placed in a stainless steel hollow cylindrical mold with a diameter of 10 cm and a height of 6 cm and vibrated and compacted. The mold was then placed in a high-temperature device and heated to 170 °C at a rate of 5 °C / min. The melted low-density polyethylene liquid was poured out and quickly and evenly flattened before solidification. After trimming and polishing, a 0.5 mm thick and 4*4 (cm2) area was obtained. 2 ) of low-density polyethylene sheet.

[0091] (6) The ultra-high molecular weight polyethylene porous scaffold obtained by the treatment in step (4) is tightly fitted with the low-density polyethylene sheet obtained in step (5) and then loaded into a special tetrafluoroethylene mold. The mold is placed in a sintering device and heated at 170°C for 5 minutes to melt the contact surfaces of the two and thus bond them together. After cooling, the mold is placed in an anhydrous ethanol solution for cleaning to obtain an implantable ear cartilage composite scaffold.

[0092] Comparative Example 3

[0093] For comparison, the only difference between this comparative example and Example 1 is that low-density polyethylene powder is not used. The other steps are the same as those in Example 1, specifically:

[0094] (1) 0.12 g of low-density polyethylene powder was placed in ultra-high molecular weight polyethylene spherical particles with a diameter of 10 cm and a height of 6 cm and mixed with 0.12 g of nano-hydroxyapatite particles. Anhydrous ethanol was added until the solid particles were covered with anhydrous ethanol. The mixture was mixed evenly at a speed of 500 r / min using a high-speed ball mill. After drying at room temperature, a composite powder for preparing an ultra-high molecular weight porous composite scaffold was obtained.

[0095] (2) The composite powder obtained in step (1) is placed in a special polytetrafluoroethylene mold, shaken thoroughly and fixed, and placed in a sintering device for pre-pressing treatment with a heating rate of 10°C / min, a pre-pressing sintering temperature of 150°C, a pre-pressing sintering time of 10 min, and a pre-pressing pressure of 10 MPa; and after cooling at room temperature, an ultra-high molecular weight polyethylene composite sheet is obtained.

[0096] (3) The high molecular weight polyethylene composite sheet obtained in step (2) is again loaded into a special polytetrafluoroethylene mold for sintering treatment, and the heating rate is set to 10°C / min, the sintering temperature is 185°C, and the pressure is 5 MPa. After sintering for 20 minutes, an ultra-high molecular weight polyethylene porous scaffold is obtained.

[0097] (4) The ultra-high molecular weight polyethylene porous scaffold obtained in step (3) is immersed in a mixed solution of concentrated sulfuric acid and hydrogen peroxide in a volume ratio of 1:1 for surface treatment.

[0098] (5) The ultra-high molecular weight polyethylene porous scaffold obtained by the treatment in step (4) is loaded into a special tetrafluoroethylene mold, placed in a sintering device and heated at 170°C for 5 minutes, and after cooling, it is placed in an anhydrous ethanol solution for cleaning to obtain an implantable ear cartilage scaffold.

[0099] The products prepared from Examples 1 to 5 and Comparative Examples 1 to 3 were subjected to performance tests. The test results are shown in Table 1.

[0100] It can be seen from the table that the sintering temperature and sintering time of Example 1 are the same as those of Example 2. The difference is that the spherical ultra-high molecular weight polyethylene particles of Example 2 are smaller in particle size than those of Example 1, and the internal pore size of Example 2 is smaller and the porosity is higher. The face-centered cubic stacking theory of crystal structure is cited to illustrate that the pore size of porous materials prepared by the powder sintering method is affected by the particle size.

[0101] Example 1, Example 3, and Example 4 had the same sintering time. The difference was that Examples 3 and 4 were sintered at different temperatures relative to Example 1. The experimental data in Table 1 show that Example 3 has a higher porosity but lower tensile strength than Example 1, while Example 4 has a higher tensile strength but lower porosity. This indicates that sintering temperature is a key parameter affecting the internal structure and mechanical properties of porous scaffolds during the sintering process. Different sintering temperatures can lead to different chain diffusion rates between ultra-high molecular weight polyethylene particles when powder is sintered at the same time, thereby affecting the sintering neck length and, further, the porosity and mechanical properties of the porous material.

[0102] Compared with Example 1, in Comparative Example 1, the base material was not surface treated, and the surface contact angle of the base material was 91.9°, showing hydrophobicity, indicating that surface treatment can significantly improve the affinity and hydrophobicity of the material, thereby facilitating the attachment and growth of cells and the completion of vascularization of surrounding tissues, further improving the biocompatibility of the material.

[0103] Comparative Example 2, compared to Example 1, showed no porous structure. This suggests that the ultra-high molecular weight polyethylene powder, due to its small size and larger specific surface area, heats more quickly during sintering, and more easily reaches melting temperature under external force. Consequently, the resulting scaffold lacks a porous structure. Therefore, the use of spherical ultra-high molecular weight polyethylene particles facilitates the formation of a porous structure.

[0104] Compared with Example 1, the tensile strength of Comparative Example 3 is significantly lower than that of Comparative Example 1, indicating that by selecting appropriate sintering parameters and ensuring that the porous scaffold has a porosity and pore size distribution suitable for cell adhesion and tissue growth, its mechanical properties can be improved by compounding low-density polyethylene sheets, thereby meeting surgical requirements.

[0105] Table 1 Experimental results of contact angle and porosity of examples and comparative examples

[0106]

Claims

1. A method for preparing an implantable ear cartilage composite scaffold, characterized by: The specific steps include: (1) adding ultra-high molecular weight polyethylene particles and hydroxyapatite powder to an ethanol solution and mixing them uniformly by ball milling, and then drying them at room temperature to obtain a composite powder for preparing an ultra-high molecular weight porous composite scaffold; the ultra-high molecular weight polyethylene particles have a particle size between 10 mesh and 200 mesh, and a molecular weight between 150w and 1000w; (2) The composite powder obtained in step (1) is placed in a special polytetrafluoroethylene mold, fully shaken and fixed, and pre-pressed, and then cooled to obtain an ultra-high molecular weight polyethylene composite sheet; (3) hot-pressing and sintering the ultra-high molecular weight polyethylene composite sheet obtained after the pre-pressing treatment in step (2), and cooling it to room temperature to obtain an ultra-high molecular weight polyethylene matrix material; (4) Soaking the ultra-high molecular weight polyethylene matrix material obtained in step (3) in a mixed solution of concentrated sulfuric acid and hydrogen peroxide for 10 min to 15 min; (5) Low-density polyethylene powder is placed in a homemade stainless steel cylindrical mold and oscillated and compacted. The mold is then placed in a high-temperature device for melting. The resulting low-density polyethylene molten liquid is poured out and quickly and evenly flattened before solidification. Low-density polyethylene sheets with uniform thickness are obtained through trimming and polishing. (6) The ultra-high molecular weight polyethylene matrix material treated with a mixed solution of concentrated sulfuric acid and hydrogen peroxide in step (4) is laminated with the surface of the low-density polyethylene sheet obtained in step (5) and then placed in a special polytetrafluoroethylene mold. The mold is then heated in a sintering device to melt the contact surfaces of the two and bond them together. After cooling, the mold is placed in an ethanol solution for cleaning.

2. The method for preparing the implantable ear cartilage composite scaffold according to claim 1, characterized in that: The mass percentage of hydroxyapatite added in step (1) is 0-20% of the ultra-high molecular weight polyethylene particles, and the mass percentage of hydroxyapatite added is not 0%, and the hydroxyapatite is in nano or micro state.

3. The method for preparing the implantable ear cartilage composite scaffold according to claim 1, characterized in that: The heating rate of the pre-pressing treatment in step (2) is 5-10°C / min, the temperature is 100-180°C, the pressure is 0-50MPa, and the treatment time is 5min-15min.

4. The method for preparing the implantable ear cartilage composite scaffold according to claim 1, characterized in that: In step (3), the heating rate of hot pressing sintering is 5°C / min-10°C / min, the temperature is 100-200°C, the pressure is 5 MPa, the sintering time is 10 min-30 min, and the thickness of the prepared ultra-high molecular weight polyethylene matrix material is 0.5 mm-5 mm, and the internal pore size is 50 μm-200 μm.

5. The method for preparing the implantable ear cartilage composite scaffold according to claim 1, characterized in that: In step (4), the volume ratio of concentrated sulfuric acid to hydrogen peroxide is 1:1, and the mass concentration of the concentrated sulfuric acid used is 1.84 g / ml.

6. The method for preparing the implantable ear cartilage composite scaffold according to claim 1, characterized in that: In step (5), the heating rate is 5°C / min-10°C / min, the melting temperature is 100°C-180°C, the melting time is 10min-15min, and the thickness of the prepared low-density polyethylene sheet is 0.2mm-5mm.

7. The method for preparing the implantable ear cartilage composite scaffold according to claim 1, characterized in that: The mold described in step (5) is a stainless steel hollow cylindrical mold, and the mold can be clamped by tongs.

8. The method for preparing the implantable ear cartilage composite scaffold according to claim 1, characterized in that: The specially made polytetrafluoroethylene molds described in step (2) and step (6) are divided into a solid male mold and a solid female mold. The interior of the solid female mold is a hollow part of 4 cm × 4 cm × 1 cm. The solid female mold and the solid male mold can fit tightly.

9. The method for preparing the implantable ear cartilage composite scaffold according to claim 1, characterized in that: The sintering temperature in step (6) is 100-180°C, and the sintering time is 5 min-8 min.

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