A preparation method for 4D printed intelligent near-infrared responsive bone filling implant

Abstract

A preparation method of a 4D printed intelligent near-infrared responsive bone filling implant, belonging to the field of orthopedic biomedical materials, comprises the following steps: step one: preparation of a composite material for 4D printing; step two: construction of a near-infrared responsive intelligent deformable cross-mesh structure 4D filler; the present invention selects a PLA / PCL / β-TCP complex containing magnesium nanoparticles and prints a filler for filling irregular tumor postoperative bone defects through 4D printing technology, the filler can achieve minimally invasive implantation into the bone defect cavity and then expand in volume under the irradiation of near-infrared light, thereby achieving seamless filling of the cavity; by controlling the power of an infrared instrument, the dual functions of killing residual tumor cells and tissues around the cavity and promoting osteogenesis in later stages can be achieved, and the support force generated by the volume expansion of the filler at the lesion defect on the surrounding bone tissue can effectively promote the regeneration and repair of the surrounding bone.

Description

Technical Field

[0001] The present invention belongs to the field of orthopedic biomedical materials, and in particular relates to a method for preparing a 4D printed intelligent near-infrared responsive bone filling implant. Background Art

[0002] In the field of orthopedics, some common benign tumors such as giant cell tumor of bone and fibrous dysplasia are prone to occur in young and middle-aged people. The characteristics of difficult intraoperative removal and easy recurrence not only bring long-term pain to patients, but also bring huge economic burden to their families. Among them, the recurrence rate of giant cell tumor of bone within five years after treatment is about 10% to 30%. Clinically, there is an urgent need to improve treatment methods to reduce the postoperative recurrence rate. At present, clinical treatment methods are commonly used to surgically remove local bone tumors, and then use autologous bone or artificial bone fillers to fill defects or cavities. However, for large and irregular bone defects, it is a major challenge to completely fill the defect with the selected bone implant during surgery and ensure that no gaps are left. In addition, the poor bone integration performance and poor regeneration of new bone after the bone implant fills the defect are still urgent problems that need to be solved. Incomplete resection of the tumor lesion area during surgery can easily lead to the proliferation of residual tumor cells, which will further promote tumor recurrence and even metastasis.

[0003] In order to improve the treatment effect of bone tumors, it is urgent to develop a multifunctional filler with both bone remodeling ability and tumor eradication ability. Among the many factors that affect cell activity, the influence of temperature on cells is multifaceted. For example, at 41°C, proteins in cells are denatured. In addition, in an environment of 45 to 48°C, tumor cells will rapidly necrotize, and when exposed to more than 48°C, most cells will face death. In recent years, near-infrared (NIR) light-assisted photothermal therapy (PTT) has been widely used in tumor treatment. It has the ability to penetrate deep tissues through non-invasive and remote precise control, making it an ideal choice for effective treatment. Specifically, PTT utilizes the ability of photothermal agents to effectively convert near-infrared light energy into heat when exposed to near-infrared radiation, which causes a local temperature increase of 45-48°C in tissues, thereby achieving thermal ablation of cancer cells.

[0004] In addition, some studies have shown that an environment of 42°C is conducive to the osteogenesis of stem cells. Studies have successfully confirmed that bone filling materials mixed with iron nanoparticles, black phosphorus nanosheets and graphene oxide have the ability to inhibit bone tumors and promote osteogenesis under the stimulation of infrared devices of different powers. However, the degradation performance of the above materials in the body is not very significant.

[0005] The good biocompatibility and photothermal conversion effect of magnesium nanoparticles make them also suitable for hyperthermia. In addition, magnesium nanoparticles with good biodegradability can release Mg2+ To promote osteogenesis.

[0006] Some groundbreaking studies have used 3D printing technology to create cutting-edge dual-functional bone fillers that can effectively inhibit bone tumors and stimulate bone regeneration using near-infrared light. 3D printing technology has been used to create cutting-edge dual-functional bone fillers that can effectively inhibit bone tumors and stimulate bone regeneration using near-infrared light. Despite the extraordinary capabilities of these customizable fillers, personalized reconstruction of bone tissue for extensive and irregular bone defects remains a complex challenge. In response to the above issues, the emergence of 4D printing technology has attracted widespread attention. Compared with 3D printing, 4D printing introduces an additional time dimension, allowing the structures produced by this method to deform over time in response to external stimuli. Structures produced by 4D printing can be dynamically reconfigured over time in response to different stimuli, thus overcoming the limitations of 3D bioprinting.

[0007] Among the raw materials selected in the present invention, polylactic acid (PLA) is a biodegradable plastic polymerized from lactic acid. Its excellent biocompatibility and degradability have attracted wide attention and application in the medical field and sustainable development field. Its unique shape memory property also gives it the feasibility of 4D printing. Polycaprolactone (PCL) has good plasticity and biocompatibility and is widely used in the medical field. β-tricalcium phosphate (β-TCP) is a bioceramic material widely used in the medical field. Adding β-TCP to PLA or PCL can achieve the osteogenic properties of the material to a certain extent. And magnesium metal materials have also become a research hotspot in various medical fields in recent years due to their degradable properties.

[0008] For the internal structure used by the stent of the present invention, the cross-curve mesh structure has certain negative Poisson's ratio and zero Poisson's ratio effects. Although it has been studied a little, it has not yet been applied to the preparation of bone filling implants in the medical field. The present invention combines the advantages of a degradable composite material with a cross-curve mesh structure to invent a 4D printed intelligent near-infrared responsive bone filling implant. Summary of the invention

[0009] The purpose of the present invention is to solve the problems existing in the above-mentioned background technology and to provide a preparation method of a 4D printed intelligent near-infrared responsive bone filling implant.

[0010] The present invention selects a PLA / PCL / β-TCP complex containing magnesium nanoparticles and uses 4D printing technology to print a filler for filling irregular tumor postoperative bone defects. The filler can achieve minimally invasive implantation into the bone defect cavity and expand in volume under the irradiation of near-infrared light, thereby achieving seamless filling of the cavity. In addition, by controlling the power of the infrared instrument, the dual functions of killing residual tumor cells and tissues around the cavity and promoting osteogenesis in the later stages can be achieved. The support force generated by the volume expansion of the filler at the lesion defect on the surrounding bone tissue can effectively promote the regeneration and repair of the surrounding bone.

[0011] A method for preparing a 4D printed intelligent near-infrared responsive bone filling implant comprises the following steps:

[0012] Step 1: Preparation of composite materials for 4D printing

[0013] First, a PLA / PCL composite material with a mass ratio of PLA to PCL of 8:2 was prepared, and then 10wt% of β-TCP was mixed into the PLA / PCL / β-TCP composite material to prepare a PLA / PCL / β-TCP composite material; 1wt%-80wt% of magnesium nanoparticles were added to the PLA / PCL / β-TCP composite material to prepare a composite material containing magnesium nanoparticles;

[0014] Step 2: Constructing a near-infrared responsive intelligently deformable cross-mesh 4D filler

[0015] The three-dimensional model of the present invention is designed according to the 4D deformation requirements of the filler using solidworks software, and the fillers containing different mass fractions of magnesium nanoparticles are printed separately using a fused deposition modeling (FDM) (FDM) 3D printer after slicing using Simplify 3D software; during the printing process, the deformation rate and mechanical strength of the filler can be adjusted by setting different filling rates.

[0016] Step 3: In vitro shaping of near-infrared responsive intelligently deformable cross-mesh 4D filler

[0017] The near-infrared responsive intelligently deformable cross-mesh structure 4D filler is immersed in clean warm water at 48°C. At this time, an external force is applied to reduce its volume, and then it is cooled at room temperature for 30 seconds to be shaped into the required small-volume implant.

[0018] Step 4: When the shaped near-infrared responsive intelligent deformable cross-mesh structure 4D filler is used for postoperative filling of bone tumors, the magnesium nanoparticles inside the filler respond to the irradiation of the infrared device and produce a photothermal effect, so that the temperature of the filler itself gradually increases from room temperature to the 48°C required for the deformation of the filler. The heating rate and upper limit of the filler can be adjusted by regulating the power of the near-infrared, thereby achieving osteogenesis at 42°C and better tumor elimination effect at temperatures above 48°C.

[0019] Preferably, in step 1, the molecular weight of the PLA is 1×10 3 ~1×10 6 .

[0020] Preferably, in step 1, the molecular weight of PCL is 5×10 3 ~3×10 5 .

[0021] Preferably, in step 1, the proportion of β-TCP is 1wt%-80wt%.

[0022] Preferably, in step 1, the ratio of the magnesium nanoparticles is 1wt%-80wt%.

[0023] Preferably, in step 2, the ratio of the magnesium nanoparticles is 1wt%-80wt%.

[0024] Preferably, in step 2, the filling rate is set to 40%-60% during the printing process.

[0025] 80 wt%” is an abbreviation for mass percentage, which can also be expressed as “80% by weight”. It indicates the percentage of the mass of a substance in a mixture to the total mass of the mixture.

[0026] The working principle and working process of the present invention:

[0027] The filler of the present invention can produce a photothermal conversion effect under near infrared to increase the local temperature, and when the temperature rises to the glass transition temperature (Tg) of the composite material used for the filler or above, the filler can undergo a glass transition. In short, the filler can be deformed under the action of an external force, and after the temperature of the filler cools down, the filler shape can be fixed to the plastic shape, and when the temperature rises to Tg or above again, the filler will restore its original shape again. This property is the shape memory property.

[0028] The present invention can realize the following four functions simultaneously:

[0029] (1) When the filling material of the present invention is used to fill the bone defect after bone tumor surgery, the filler deforms and increases in volume, thereby perfectly and seamlessly filling the bone defect after tumor surgery;

[0030] (2) The filler undergoes near-infrared response deformation and the filler temperature rises to 48°C to eliminate the tumor around the defect;

[0031] (3) After the filler undergoes near-infrared response deformation, the filler temperature rises to 42°C, which can promote osteogenesis. In addition, the subsequent Mg 2+ The release of can also further promote osteogenesis around the defect;

[0032] (4) During surgery, the filler expands in volume under near-infrared response, which provides continuous support for the surrounding bone tissue, thereby promoting the regeneration of the surrounding bone tissue.

[0033] Beneficial effects of the present invention:

[0034] (1) The PLA / PCL in the filler of the present invention has good shape memory properties. In addition, the magnesium nanoparticles contained in the composite material can respond to near-infrared light to increase the temperature of the entire filler to 48°C, thereby achieving deformation and expansion of the filler under infrared irradiation after implantation to complete the precise filling of the defect after tumor surgery.

[0035] (2) When the filler of the present invention is exposed to external near-infrared irradiation, the volume of the filler expands and the temperature of the filler rises to 48°C, thereby killing surrounding tumor cells and tissues. It can effectively prevent the recurrence of the lesion area after surgery.

[0036] (3) In addition to the above-mentioned precise filling and infrared thermotherapy anti-tumor properties, the filler of the present invention has the function of promoting surrounding osteogenesis when exposed to exogenous near-infrared irradiation at a temperature of 42°C. In addition, as the composite material degrades, Mg 2+ The sustained release of can also further promote osteogenesis, effectively solving the problem of poor bone regeneration in the postoperative lesion defect.

[0037] (4) The filler of the present invention expands in volume under near-infrared response during surgery, generating a continuous supporting force for the surrounding bone tissue, thereby promoting the regeneration of the surrounding bone. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 These are SEM images of fillers printed with materials of various mass fractions in Example 1 of the present invention.

[0039] Figure 2 : 4D deformation images of the fillers printed with materials of various mass fractions in Example 1 of the present invention.

[0040] Figure 3 : This is a photothermal conversion effect diagram of the filler printed with various mass fractions of materials under infrared irradiation in Example 1 of the present invention.

[0041] Figure 4 : This is a diagram showing the osteogenic effect of printing fillers with various mass fractions of materials in Example 1 of the present invention.

[0042] Figure 5 : A side view of the internal structure of the filler designed in Example 1 of the present invention.

[0043] Figure 6 : A top view of the internal structure of the filler designed in Example 1 of the present invention.

[0044] Figure 7 : Actual pictures of the filler before and after deformation, which is printed out from the composite material containing 7.5wt% magnesium nanoparticles in Example 1 of the present invention and has a filling rate of 40%.

[0045] Figure 8 : Actual pictures of the filler before and after deformation, which is printed out from the composite material containing 7.5wt% magnesium nanoparticles in Example 1 of the present invention and has a filling rate of 50%.

[0046] Fig. 9 : Actual pictures of the filler before and after deformation, which is printed out from the composite material containing 7.5wt% magnesium nanoparticles in Example 1 of the present invention and has a filling rate of 60%. DETAILED DESCRIPTION

[0047] See also Figures 1 to 9 Shown is an embodiment of the present invention. Example 1

[0048] A method for preparing a 4D printed intelligent near-infrared responsive bone filling implant comprises the following steps:

[0049] Step 1: Preparation of composite materials for 4D printing

[0050] The molecular weight is 8×10 4 PLA and molecular weight is 8×10 4 PCL was mixed in a ratio of 8:2 through an internal mixer to prepare a PLA / PCL composite material, and 10wt% of β-TCP was mixed with the above materials. Magnesium nanoparticles with a diameter of 10-100mm after sifting through a 100-mesh sieve were mixed into PLA / PCL / β-TCP at a ratio of 2.5wt%, 5wt%, 7.5wt% and 10wt% at 200°C for use.

[0051] Step 2: Constructing a near-infrared responsive intelligently deformable cross-mesh 4D filler

[0052] The three-dimensional model of the linear mesh structure was designed by Solidworks three-dimensional modeling software and saved in STL format. The model was then imported into Simplify 3D software for slicing, and the obtained g-code was input into the FDM 3D printer to print fillers containing different mass fractions of magnesium nanoparticles. The surface morphology of the printed fillers was observed and analyzed by scanning electron microscopy (SEM). Figure 1 shown. Figure 2 The 4D deformation performance of 4D printed smart infrared responsive composite materials was demonstrated. Figure 3 The good photothermal conversion efficiency of the implant material of the present invention at a power of 1.5W was verified, confirming the potential of the filler for anti-tumor performance. Figure 4 The osteogenic performance of each group of fillers was verified by alkaline phosphatase staining, and the composite material containing 7.5% magnesium nanoparticles with the best comprehensive osteogenic and deformation effects was selected for subsequent implementation of the present invention.

[0053] Step 3: In vitro shaping of near-infrared responsive intelligently deformable cross-mesh 4D filler

[0054] The near-infrared responsive intelligently deformable cross-mesh structure 4D filler is immersed in clean warm water at 48°C. At this time, an external force is applied to reduce its volume, and then it is cooled at room temperature for 30 seconds to be shaped into the required small-volume implant.

[0055] Step 4: When the shaped near-infrared responsive small-volume intelligent deformable cross-mesh structure 4D filler is used for postoperative filling of bone tumors, the shaped volume of the intelligent deformable cross-mesh structure 4D filler becomes smaller and the magnesium nanoparticles inside the filler respond under the irradiation of the infrared device to produce a photothermal effect, which gradually increases the temperature of the filler itself from room temperature 22°C to the 48°C required for the deformation of the filler within 30 seconds. The heating rate and upper limit of the filler can be adjusted by regulating the power of the near-infrared, thereby achieving osteogenesis at 42°C and better tumor elimination effect at temperatures above 48°C.

[0056] Design and printing of the structure of this embodiment:

[0057] In order to make the filler more suitable for minimally invasive implantation after plasticization and restoration, this embodiment designs a filler with an internal cross-net structure to meet the requirements that during the shaping process, the filler is compressed in one direction when subjected to external force, while the other direction remains unchanged. The three-dimensional model of the curved net structure is designed using Solidworks three-dimensional modeling software, such as Figure 5 and Figure 6As shown in the figure, the two are the side view and top view of the internal structure of the structure respectively; the three-dimensional model is saved in STL format. The model is imported into Simplify 3D software for slicing, and the filling rate is set to 40%. The obtained g-code code is transferred to the FDM type 3D printer to print the filler with a mass fraction of 7.5% of magnesium nanoparticles. Figure 7 It was demonstrated that 4D printed implants with a filling rate of 40% have good deformation properties and potential minimally invasive implantability. Example 2

[0058] A method for preparing a 4D printed intelligent near-infrared responsive bone filling implant comprises the following steps:

[0059] Step 1: Preparation of composite materials for 4D printing

[0060] The molecular weight is 8×10 4 PLA and molecular weight is 8×10 4 PCL was mixed in a ratio of 8:2 by an internal mixer to prepare a PLA / PCL composite material, and 10wt% of β-TCP was mixed into the above materials. Magnesium nanoparticles with a diameter of 10-100mm after sifting through a 100-mesh sieve were mixed into PLA / PCL / β-TCP at a ratio of 7.5wt% at 200°C for use.

[0061] Step 2: Constructing a near-infrared responsive intelligently deformable cross-mesh 4D filler

[0062] The 3D model of the curved mesh structure was designed using Solidworks 3D modeling software and saved in STL format. The model was then imported into Simplify 3D software for slicing, the internal filling rate of the implant was set to 50%, and the resulting g-code was transferred to an FDM 3D printer. Figure 8 Shown are the deformation properties of an implant with a 50% filling ratio.

[0063] Step 3: In vitro shaping of near-infrared responsive intelligently deformable cross-mesh 4D filler

[0064] The near-infrared responsive intelligently deformable cross-mesh structure 4D filler is immersed in clean warm water at 48°C. At this time, an external force is applied to reduce its volume, and then it is cooled at room temperature for 30 seconds to be shaped into the required small-volume implant.

[0065] Step 4: When the shaped near-infrared responsive intelligent deformable cross-mesh structure 4D filler is used for postoperative filling of bone tumors, the magnesium nanoparticles inside the filler respond to the irradiation of the infrared device and produce a photothermal effect, so that the temperature of the filler itself gradually increases from room temperature to the 48°C required for the deformation of the filler. The heating rate and upper limit of the filler can be adjusted by regulating the power of the near-infrared, thereby achieving osteogenesis at 42°C and better tumor elimination effect at temperatures above 48°C. Example 3

[0066] A method for preparing a 4D printed intelligent near-infrared responsive bone filling implant comprises the following steps:

[0067] Step 1: Preparation of composite materials for 4D printing

[0068] The molecular weight is 8×10 4 PLA and molecular weight is 8×10 4 PCL was mixed in a ratio of 8:2 by an internal mixer to prepare a PLA / PCL composite material, and 10wt% of β-TCP was mixed into the above materials. Magnesium nanoparticles with a diameter of 10-100mm after sifting through a 100-mesh sieve were mixed into PLA / PCL / β-TCP at a ratio of 7.5wt% at 200°C for use.

[0069] Step 2: Constructing a near-infrared responsive intelligently deformable cross-mesh 4D filler

[0070] The 3D model of the curved mesh structure was designed using Solidworks 3D modeling software and saved in STL format. The model was then imported into Simplify 3D software for slicing, the internal filling rate of the implant was set to 60%, and the resulting g-code was transferred to an FDM 3D printer. Fig. 9 Shown are the deformation properties of an implant with a filling ratio of 60%.

[0071] Step 3: In vitro shaping of near-infrared responsive intelligently deformable cross-mesh 4D filler

[0072] The near-infrared responsive intelligently deformable cross-mesh structure 4D filler is immersed in clean warm water at 48°C. At this time, an external force is applied to reduce its volume, and then it is cooled at room temperature for 30 seconds to be shaped into the required small-volume implant.

[0073] Step 4: When the shaped near-infrared responsive intelligent deformable cross-mesh structure 4D filler is used for postoperative filling of bone tumors, the magnesium nanoparticles inside the filler respond to the irradiation of the infrared device and produce a photothermal effect, so that the temperature of the filler itself gradually increases from room temperature to the 48°C required for the deformation of the filler. The heating rate and upper limit of the filler can be adjusted by regulating the power of the near-infrared, thereby achieving osteogenesis at 42°C and better tumor elimination effect at temperatures above 48°C. Example 4

[0074] A method for preparing a 4D printed intelligent near-infrared responsive bone filling implant comprises the following steps:

[0075] Step 1: Preparation of composite materials for 4D printing

[0076] The molecular weight is 10×10 4 PLA and molecular weight is 10×10 4 PCL was mixed in a ratio of 8:2 by an internal mixer to prepare a PLA / PCL composite material, and 10wt% of β-TCP was mixed into the above materials. Magnesium nanoparticles with a diameter of 10-100mm after sifting through a 100-mesh sieve were mixed into PLA / PCL / β-TCP at a ratio of 7.5wt% at 200°C for use.

[0077] Step 2: Constructing a near-infrared responsive intelligently deformable cross-mesh 4D filler

[0078] The 3D model of the curved mesh structure was designed using Solidworks 3D modeling software and saved in STL format. The model was then imported into Simplify 3D software for slicing, the internal filling rate of the implant was set to 60%, and the resulting g-code was transferred to an FDM 3D printer. Fig. 9 Shown are the deformation properties of an implant with a filling ratio of 60%.

[0079] Step 3: In vitro shaping of near-infrared responsive intelligently deformable cross-mesh 4D filler

[0080] The near-infrared responsive intelligently deformable cross-mesh structure 4D filler is immersed in clean warm water at 48°C. At this time, an external force is applied to reduce its volume, and then it is cooled at room temperature for 30 seconds to be shaped into the required small-volume implant.

[0081] Step 4: When the shaped near-infrared responsive intelligent deformable cross-mesh structure 4D filler is used for postoperative filling of bone tumors, the magnesium nanoparticles inside the filler respond to the irradiation of the infrared device and produce a photothermal effect, so that the temperature of the filler itself gradually increases from room temperature to the 48°C required for the deformation of the filler. The heating rate and upper limit of the filler can be adjusted by regulating the power of the near-infrared, thereby achieving osteogenesis at 42°C and better tumor elimination effect at temperatures above 48°C. Example 5

[0082] A method for preparing a 4D printed intelligent near-infrared responsive bone filling implant comprises the following steps:

[0083] Step 1: Preparation of composite materials for 4D printing

[0084] The molecular weight is 12×10 4 PLA and molecular weight is 12×10 4 PCL was mixed in a ratio of 8:2 by an internal mixer to prepare a PLA / PCL composite material, and 10wt% of β-TCP was mixed into the above materials. Magnesium nanoparticles with a diameter of 10-100mm after sifting through a 100-mesh sieve were mixed into PLA / PCL / β-TCP at a ratio of 7.5wt% at 200°C for use.

[0085] Step 2: Constructing a near-infrared responsive intelligently deformable cross-mesh 4D filler

[0086] The 3D model of the curved mesh structure was designed using Solidworks 3D modeling software and saved in STL format. The model was then imported into Simplify 3D software for slicing, the internal filling rate of the implant was set to 60%, and the resulting g-code was transferred to an FDM 3D printer. Fig. 9 Shown are the deformation properties of an implant with a filling ratio of 60%.

[0087] Step 3: In vitro shaping of near-infrared responsive intelligently deformable cross-mesh 4D filler

[0088] The near-infrared responsive intelligently deformable cross-mesh structure 4D filler is immersed in clean warm water at 48°C. At this time, an external force is applied to reduce its volume, and then it is cooled at room temperature for 30 seconds to be shaped into the required small-volume implant.

[0089] Step 4: When the shaped near-infrared responsive intelligent deformable cross-mesh structure 4D filler is used for postoperative filling of bone tumors, the magnesium nanoparticles inside the filler respond to the irradiation of the infrared device and produce a photothermal effect, so that the temperature of the filler itself gradually increases from room temperature to the 48°C required for the deformation of the filler. The heating rate and upper limit of the filler can be adjusted by regulating the power of the near-infrared, thereby achieving osteogenesis at 42°C and better tumor elimination effect at temperatures above 48°C. Example 6

[0090] A method for preparing a 4D printed intelligent near-infrared responsive bone filling implant comprises the following steps:

[0091] Step 1: Preparation of composite materials for 4D printing

[0092] The molecular weight is 14×10 4 PLA and molecular weight is 14×10 4 PCL was mixed in a ratio of 8:2 by an internal mixer to prepare a PLA / PCL composite material, and 10wt% of β-TCP was mixed into the above materials. Magnesium nanoparticles with a diameter of 10-100mm after sifting through a 100-mesh sieve were mixed into PLA / PCL / β-TCP at a ratio of 7.5wt% at 200°C for use.

[0093] Step 2: Constructing a near-infrared responsive intelligently deformable cross-mesh 4D filler

[0094] The 3D model of the curved mesh structure was designed using Solidworks 3D modeling software and saved in STL format. The model was then imported into Simplify 3D software for slicing, the internal filling rate of the implant was set to 60%, and the resulting g-code was transferred to an FDM 3D printer. Fig. 9 Shown are the deformation properties of an implant with a filling ratio of 60%.

[0095] Step 3: In vitro shaping of near-infrared responsive intelligently deformable cross-mesh 4D filler

[0096] The near-infrared responsive intelligently deformable cross-mesh structure 4D filler is immersed in clean warm water at 48°C. At this time, an external force is applied to reduce its volume, and then it is cooled at room temperature for 30 seconds to be shaped into the required small-volume implant.

[0097] Step 4: When the shaped near-infrared responsive intelligent deformable cross-mesh structure 4D filler is used for postoperative filling of bone tumors, the magnesium nanoparticles inside the filler respond to the irradiation of the infrared device and produce a photothermal effect, so that the temperature of the filler itself gradually increases from room temperature to the 48°C required for the deformation of the filler. The heating rate and upper limit of the filler can be adjusted by regulating the power of the near-infrared, thereby achieving osteogenesis at 42°C and better tumor elimination effect at temperatures above 48°C.

[0098] Through the design of material distribution and model structure in Example 1, Example 2, Example 3, Example 4, Example 5, and Example 6, the printed implant can achieve different degrees of expansion, and its change rule is controllable. The above is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention can have various changes and variations. Any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a 4D printed intelligent near-infrared responsive bone filling implant, characterized in that In: The steps include: Step 1: Preparation of composite materials for 4D printing First, a PLA / PCL composite material with a mass ratio of PLA to PCL of 8:2 was prepared, and then 10wt% of β-TCP was mixed into the PLA / PCL / β-TCP composite material to prepare a PLA / PCL / β-TCP composite material; 1wt%-80wt% of magnesium nanoparticles were added to the PLA / PCL / β-TCP composite material to prepare a composite material containing magnesium nanoparticles; Step 2: Constructing a near-infrared responsive intelligently deformable cross-mesh 4D filler The three-dimensional model of the present invention is designed using solidworks software according to the 4D deformation requirements of the filler. The interior of the model is designed as a cross-net structure, which allows the filler to be compressed in one direction in the horizontal and vertical directions during the shaping process, while the other direction remains unchanged when subjected to external force, so that it has minimally invasive implantation performance. After slicing using Simplify3D software, fillers containing different mass fractions of magnesium nanoparticles are printed using a fused deposition modeling 3D printer; During the printing process, the deformation rate and mechanical strength of the filler can be adjusted by setting different filling rates; Step 3: In vitro shaping of near-infrared responsive intelligently deformable cross-mesh 4D filler The near-infrared responsive intelligently deformable cross-mesh structure 4D filler is immersed in clean warm water at 48°C. At this time, an external force is applied to reduce its volume, and then it is cooled at room temperature for 30 seconds to be shaped into the required small-volume implant; Step 4: When the shaped near-infrared responsive small-volume intelligent deformable cross-mesh structure 4D filler is used for postoperative filling of bone tumors, the shaped volume of the intelligent deformable cross-mesh structure 4D filler becomes smaller and the magnesium nanoparticles inside the filler respond under the irradiation of the infrared device to produce a photothermal effect, which gradually increases the temperature of the filler itself from room temperature 22°C to the 48°C required for the deformation of the filler within 30 seconds. The heating rate and upper limit of the filler can be adjusted by regulating the power of the near-infrared, thereby achieving osteogenesis at 42°C and better tumor elimination effect at temperatures above 48°C.

2. The method for preparing a 4D printed intelligent near-infrared responsive bone filling implant according to claim 1, characterized in that: In step 1, the molecular weight of the PLA is 1×10 3 ~1×10 6 .

3. The method for preparing a 4D printed intelligent near-infrared responsive bone filling implant according to claim 1, characterized in that: In step 1, the molecular weight of PCL is 5×10 3 ~3×10 5 .

4. The method for preparing a 4D printed intelligent near-infrared responsive bone filling implant according to claim 1, characterized in that: In step 2, the filling rate is set to 40%-60% during the printing process.

Images